---
_id: '15084'
abstract:
- lang: eng
text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
terminals in the brain, except in medial habenula (MHb) terminals, which show
robust potentiation. However, mechanisms underlying this enigmatic potentiation
remain elusive. Here, we report that GBR activation on MHb terminals induces an
activity-dependent transition from a facilitating, tonic to a depressing, phasic
neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing
phasic release exhibits looser coupling distance than the tonic release. Furthermore,
the tonic and phasic release are selectively affected by deletion of synaptoporin
(SPO) and Ca\r\n 2+\r\n -dependent
activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation,
the short-term plasticity associated with tonic release, and CAPS2 retains the
increased RRP for initial responses in phasic response trains. The cytosolic protein
CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane
protein SPO, and they were colocalized in the same terminals. We developed the
“Flash and Freeze-fracture” method, and revealed the release of SPO-associated
vesicles in both tonic and phasic modes and activity-dependent recruitment of
CAPS2 to the AZ during phasic release, which lasted several minutes. Overall,
these results indicate that GBR activation translocates CAPS2 to the AZ along
with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP
increase. Thus, we identified structural and molecular mechanisms underlying tonic
and phasic neurotransmitter release and their transition by GBR activation in
MHb terminals."
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript.
This project has received funding from the European Research Council (ERC) and European
Commission, under the European Union’s Horizon 2020 research and innovation program
(ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement
no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of
Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi
for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for
the design of the slice recovery chamber for Flash and Freeze experiments, Todor
Asenov from the ISTA machine shop for custom part preparations for high-pressure
freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities
for technical support.
article_number: e2301449121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Hüseyin C
full_name: Önal, Hüseyin C
id: 4659D740-F248-11E8-B48F-1D18A9856A87
last_name: Önal
orcid: 0000-0002-2771-2011
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Utsa
full_name: Roy, Utsa
id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2
last_name: Roy
- first_name: Yukihiro
full_name: Nakamura, Yukihiro
last_name: Nakamura
- first_name: Tetsushi
full_name: Sadakata, Tetsushi
last_name: Sadakata
- first_name: Makoto
full_name: Sanbo, Makoto
last_name: Sanbo
- first_name: Masumi
full_name: Hirabayashi, Masumi
last_name: Hirabayashi
- first_name: JeongSeop
full_name: Rhee, JeongSeop
last_name: Rhee
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release
from medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences. 2024;121(8).
doi:10.1073/pnas.2301449121
apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier,
E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences. Proceedings
of the National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121
chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane,
Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce
Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment
of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences.
Proceedings of the National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121.
ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles,” Proceedings of the National Academy of Sciences, vol. 121, no.
8. Proceedings of the National Academy of Sciences, 2024.
ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U,
Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto
R. 2024. GABAB receptors induce phasic release from medial habenula terminals
through activity-dependent recruitment of release-ready vesicles. Proceedings
of the National Academy of Sciences. 121(8), e2301449121.
mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial
Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.”
Proceedings of the National Academy of Sciences, vol. 121, no. 8, e2301449121,
Proceedings of the National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121.
short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier,
U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose,
P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences 121
(2024).
date_created: 2024-03-05T09:23:55Z
date_published: 2024-02-20T00:00:00Z
date_updated: 2024-03-12T13:44:18Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.1073/pnas.2301449121
ec_funded: 1
external_id:
pmid:
- '38346189'
file:
- access_level: open_access
checksum: b25b2a057c266ff317a48b0d54d6fc8a
content_type: application/pdf
creator: dernst
date_created: 2024-03-12T13:42:42Z
date_updated: 2024-03-12T13:42:42Z
file_id: '15110'
file_name: 2024_PNAS_Koppensteiner.pdf
file_size: 13648221
relation: main_file
success: 1
file_date_updated: 2024-03-12T13:42:42Z
has_accepted_license: '1'
intvolume: ' 121'
issue: '8'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/
record:
- id: '13173'
relation: research_data
status: public
status: public
title: GABAB receptors induce phasic release from medial habenula terminals through
activity-dependent recruitment of release-ready vesicles
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 121
year: '2024'
...
---
_id: '14843'
abstract:
- lang: eng
text: The coupling between Ca2+ channels and release sensors is a key factor defining
the signaling properties of a synapse. However, the coupling nanotopography at
many synapses remains unknown, and it is unclear how it changes during development.
To address these questions, we examined coupling at the cerebellar inhibitory
basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
by paired recording and intracellular pipette perfusion revealed that the effects
of exogenous Ca2+ chelators decreased during development, despite constant reliance
of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
vesicles were only clustered at later developmental stages. Modeling suggested
a developmental transformation from a more random to a more clustered coupling
nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
for advice on numerical solution of partial differential equations, Maria Reva for
help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
and Machine Shop). The project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: No
article_type: original
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002
apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., &
Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography
at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002
chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d.
https://doi.org/10.1016/j.neuron.2023.12.002.
ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse,” Neuron. Elsevier.
ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental
transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.
Neuron.
mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002.
short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
Neuron (n.d.).
date_created: 2024-01-21T23:00:56Z
date_published: 2024-01-11T00:00:00Z
date_updated: 2024-03-14T13:14:18Z
day: '11'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
pmid:
- '38215739'
language:
- iso: eng
month: '01'
oa_version: None
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: inpress
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
record:
- id: '15101'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '15117'
abstract:
- lang: eng
text: 'The hippocampal mossy fiber synapse, formed between axons of dentate gyrus
granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the
trisynaptic circuitry of the hippocampus. Because of its comparatively large size,
this synapse is accessible to direct presynaptic recording, allowing a rigorous
investigation of the biophysical mechanisms of synaptic transmission and plasticity.
Furthermore, because of its placement in the very center of the hippocampal memory
circuit, this synapse seems to be critically involved in several higher network
functions, such as learning, memory, pattern separation, and pattern completion.
Recent work based on new technologies in both nanoanatomy and nanophysiology,
including presynaptic patch-clamp recording, paired recording, super-resolution
light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy,
has provided new insights into the structure, biophysics, and network function
of this intriguing synapse. This brings us one step closer to answering a fundamental
question in neuroscience: how basic synaptic properties shape higher network computations.'
acknowledgement: "We thank previous students, postdocs, and collaborators, particularly
J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane,
D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li,
K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston,
and N. Vyleta for their outstanding experimental contributions. We also thank P.
Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically
reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and
L. Slomianka for useful discussions. We apologize that, due to space constraints,
not all relevant papers could be cited.\r\nThis project was supported by the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der
Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone
grant), both to P.J."
article_processing_charge: No
article_type: review
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant”
cortical presynaptic terminal. Science. 2024;383(6687):eadg6757. doi:10.1126/science.adg6757
apa: Vandael, D. H., & Jonas, P. M. (2024). Structure, biophysics, and circuit
function of a “giant” cortical presynaptic terminal. Science. AAAS. https://doi.org/10.1126/science.adg6757
chicago: Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit
Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science. AAAS, 2024.
https://doi.org/10.1126/science.adg6757.
ieee: D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function
of a ‘giant’ cortical presynaptic terminal,” Science, vol. 383, no. 6687.
AAAS, p. eadg6757, 2024.
ista: Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of
a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757.
mla: Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit
Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science, vol. 383,
no. 6687, AAAS, 2024, p. eadg6757, doi:10.1126/science.adg6757.
short: D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.
date_created: 2024-03-17T23:00:57Z
date_published: 2024-03-08T00:00:00Z
date_updated: 2024-03-20T07:42:52Z
day: '08'
department:
- _id: PeJo
doi: 10.1126/science.adg6757
ec_funded: 1
external_id:
pmid:
- '38452088'
intvolume: ' 383'
issue: '6687'
language:
- iso: eng
month: '03'
oa_version: None
page: eadg6757
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
publication: Science
publication_identifier:
eissn:
- 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
scopus_import: '1'
status: public
title: Structure, biophysics, and circuit function of a "giant" cortical presynaptic
terminal
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 383
year: '2024'
...
---
_id: '12759'
abstract:
- lang: eng
text: Stereological methods for estimating the 3D particle size and density from
2D projections are essential to many research fields. These methods are, however,
prone to errors arising from undetected particle profiles due to sectioning and
limited resolution, known as ‘lost caps’. A potential solution developed by Keiding,
Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for
lost caps by quantifying the smallest detectable profile in terms of its limiting
‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the
section surface. However, this simple solution has not been widely adopted nor
tested. Rather, model-independent design-based stereological methods, which do
not explicitly account for lost caps, have come to the fore. Here, we provide
the first experimental validation of the Keiding model by comparing the size and
density of particles estimated from 2D projections with direct measurement from
3D EM reconstructions of the same tissue. We applied the Keiding model to estimate
the size and density of somata, nuclei and vesicles in the cerebellum of mice
and rats, where high packing density can be problematic for design-based methods.
Our analysis reveals a Gaussian distribution for ϕ rather than a single value.
Nevertheless, curve fits of the Keiding model to the 2D diameter distribution
accurately estimate the mean ϕ and 3D diameter distribution. While systematic
testing using simulations revealed an upper limit to determining ϕ, our analysis
shows that estimated ϕ can be used to determine the 3D particle density from the
2D density under a wide range of conditions, and this method is potentially more
accurate than minimum-size-based lost-cap corrections and disector methods. Our
results show the Keiding model provides an efficient means of accurately estimating
the size and density of particles from 2D projections even under conditions of
a high density.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: "We thank the IST Austria Electron Microscopy Facility for technical
support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments
and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048;
224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal
Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung
der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z
312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding
from the European Research Council (ERC; https://erc.europa.eu) under the European
Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692).
NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157)."
article_number: e0277148
article_processing_charge: No
article_type: original
author:
- first_name: Jason Seth
full_name: Rothman, Jason Seth
last_name: Rothman
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Noemi
full_name: Holderith, Noemi
last_name: Holderith
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: R.
full_name: Angus Silver, R.
last_name: Angus Silver
citation:
ama: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation
of a stereological method for estimating particle size and density from 2D projections
with high accuracy. PLoS ONE. 2023;18(3 March). doi:10.1371/journal.pone.0277148
apa: Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., & Angus
Silver, R. (2023). Validation of a stereological method for estimating particle
size and density from 2D projections with high accuracy. PLoS ONE. Public
Library of Science. https://doi.org/10.1371/journal.pone.0277148
chicago: Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M
Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating
Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE.
Public Library of Science, 2023. https://doi.org/10.1371/journal.pone.0277148.
ieee: J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus
Silver, “Validation of a stereological method for estimating particle size and
density from 2D projections with high accuracy,” PLoS ONE, vol. 18, no.
3 March. Public Library of Science, 2023.
ista: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023.
Validation of a stereological method for estimating particle size and density
from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148.
mla: Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating
Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE,
vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:10.1371/journal.pone.0277148.
short: J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver,
PLoS ONE 18 (2023).
date_created: 2023-03-26T22:01:07Z
date_published: 2023-03-17T00:00:00Z
date_updated: 2023-08-01T13:46:39Z
day: '17'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1371/journal.pone.0277148
ec_funded: 1
external_id:
isi:
- '001024737400001'
file:
- access_level: open_access
checksum: 2380331ec27cc87808826fc64419ac1c
content_type: application/pdf
creator: dernst
date_created: 2023-03-27T06:51:09Z
date_updated: 2023-03-27T06:51:09Z
file_id: '12770'
file_name: 2023_PLoSOne_Rothman.pdf
file_size: 7290413
relation: main_file
success: 1
file_date_updated: 2023-03-27T06:51:09Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
issue: 3 March
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00739
name: Structural plasticity at mossy fiber-CA3 synapses
publication: PLoS ONE
publication_identifier:
eissn:
- 1932-6203
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Validation of a stereological method for estimating particle size and density
from 2D projections with high accuracy
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2023'
...
---
_id: '13267'
abstract:
- lang: eng
text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
synapse level would create opportunities for decoding the dynamics and structure–function
relationships of the brain’s complex and dense information processing network;
however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
ratio and prohibitive light burden in optical imaging, whereas electron microscopy
is inherently static. Here we solved these challenges by developing an integrated
optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
enabling saturated segmentation). This leverages optical modifications to stimulated
emission depletion microscopy in comprehensively, extracellularly labeled tissue
and previous information on sample structure via machine learning to simultaneously
achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
with living tissue. This allows dense deep-learning-based instance segmentation
and 3D reconstruction at a synapse level, incorporating molecular, activity and
morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
(nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
for hardware control support and M. Cunha dos Santos for initial exploration of
software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
optics, preclinical, library and laboratory support facilities and by the Miba machine
shop. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
(B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G.N.
full_name: Grant, Seth G.N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.
ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain
tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.
ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2024-01-10T08:37:48Z
day: '01'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
isi:
- '001025621500001'
pmid:
- '37429995'
intvolume: ' 20'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41592-023-01936-6
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715767'
name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
grant_number: LT00057
name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
eissn:
- 1548-7105
issn:
- 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/LIONESS
record:
- id: '12817'
relation: research_data
status: public
- id: '14770'
relation: shorter_version
status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).
date_created: 2023-09-03T22:01:15Z
date_published: 2023-08-31T00:00:00Z
date_updated: 2024-02-21T12:18:18Z
day: '31'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41587-023-01911-8
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '13126'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '11951'
abstract:
- lang: eng
text: The mammalian hippocampal formation (HF) plays a key role in several higher
brain functions, such as spatial coding, learning and memory. Its simple circuit
architecture is often viewed as a trisynaptic loop, processing input originating
from the superficial layers of the entorhinal cortex (EC) and sending it back
to its deeper layers. Here, we show that excitatory neurons in layer 6b of the
mouse EC project to all sub-regions comprising the HF and receive input from the
CA1, thalamus and claustrum. Furthermore, their output is characterized by unique
slow-decaying excitatory postsynaptic currents capable of driving plateau-like
potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b
pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs
not only acquisition of new spatial memories, but also degradation of previously
acquired ones. Our results provide evidence of a functional role for cortical
layer 6b neurons in the adult brain.
acknowledged_ssus:
- _id: Bio
- _id: SSU
acknowledgement: We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller
for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility
of the Institute of Science and Technology Austria (ISTA) for image analysis scripts
and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel
Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for
help with single-unit clustering. Finally, we also thank B. Suter for discussions,
A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of
the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service
Units of ISTA for efficient support. This project was funded by the European Research
Council (ERC) under the European Union’s Horizon 2020 research and innovation programme
(ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).
article_number: '4826'
article_processing_charge: No
article_type: original
author:
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Karola
full_name: Käfer, Karola
id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
last_name: Käfer
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct
excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes
to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8
apa: Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &
Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons
to the hippocampus contributes to spatial coding and memory. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-022-32559-8
chicago: Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann
G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer
6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature
Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8.
ieee: Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M.
Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the
hippocampus contributes to spatial coding and memory,” Nature Communications,
vol. 13. Springer Nature, 2022.
ista: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A
direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
contributes to spatial coding and memory. Nature Communications. 13, 4826.
mla: Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer
6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature
Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8.
short: Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas,
Nature Communications 13 (2022).
date_created: 2022-08-24T08:25:50Z
date_published: 2022-08-16T00:00:00Z
date_updated: 2023-08-03T13:01:19Z
day: '16'
ddc:
- '570'
department:
- _id: JoCs
- _id: PeJo
- _id: JoDa
doi: 10.1038/s41467-022-32559-8
ec_funded: 1
external_id:
isi:
- '000841396400008'
file:
- access_level: open_access
checksum: 405936d9e4d33625d80c093c9713a91f
content_type: application/pdf
creator: dernst
date_created: 2022-08-26T11:51:40Z
date_updated: 2022-08-26T11:51:40Z
file_id: '11990'
file_name: 2022_NatureCommunications_BenSimon.pdf
file_size: 5910357
relation: main_file
success: 1
file_date_updated: 2022-08-26T11:51:40Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
- Multidisciplinary
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
contributes to spatial coding and memory
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12288'
abstract:
- lang: eng
text: To understand the function of neuronal circuits, it is crucial to disentangle
the connectivity patterns within the network. However, most tools currently used
to explore connectivity have low throughput, low selectivity, or limited accessibility.
Here, we report the development of an improved packaging system for the production
of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers
orders of magnitude higher with no background contamination, at a fraction of
the production time, while preserving the efficiency of transsynaptic labeling.
Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic
RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal
populations, tailored for diverse experimental requirements. We demonstrate the
power and flexibility of the new system by uncovering hidden local and distal
inhibitory connections in the mouse hippocampal formation and by imaging the functional
properties of a cortical microcircuit across weeks. Our novel production pipeline
provides a convenient approach to generate new rabies vectors, while our toolkit
flexibly and efficiently expands the current capacity to label, manipulate and
image the neuronal activity of interconnected neuronal circuits in vitro and in
vivo.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c
viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript.
This research was supported by the Scientific Service Units (SSU) of IST-Austria
through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical
Facility (PCF). This project was funded by the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (ERC advanced
grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der
Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier
Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).
article_number: '79848'
article_processing_charge: No
article_type: original
author:
- first_name: Anton L
full_name: Sumser, Anton L
id: 3320A096-F248-11E8-B48F-1D18A9856A87
last_name: Sumser
orcid: 0000-0002-4792-1881
- first_name: Maximilian A
full_name: Jösch, Maximilian A
id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
last_name: Jösch
orcid: 0000-0002-3937-1330
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
citation:
ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848
apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast,
high-throughput production of improved rabies viral vectors for specific, efficient
and versatile transsynaptic retrograde labeling. ELife. eLife Sciences
Publications. https://doi.org/10.7554/elife.79848
chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon.
“Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific,
Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife
Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.
ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput
production of improved rabies viral vectors for specific, efficient and versatile
transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 11, 79848.
mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies
Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.”
ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.
short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).
date_created: 2023-01-16T10:04:15Z
date_published: 2022-09-15T00:00:00Z
date_updated: 2023-08-04T10:29:48Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PeJo
doi: 10.7554/elife.79848
ec_funded: 1
external_id:
isi:
- '000892204300001'
pmid:
- '36040301'
file:
- access_level: open_access
checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T11:50:53Z
date_updated: 2023-01-30T11:50:53Z
file_id: '12463'
file_name: 2022_eLife_Sumser.pdf
file_size: 8506811
relation: main_file
success: 1
file_date_updated: 2023-01-30T11:50:53Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 266D407A-B435-11E9-9278-68D0E5697425
grant_number: LT000256
name: Neuronal networks of salience and spatial detection in the murine superior
colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1098-2017
name: Connecting sensory with motor processing in the superior colliculus
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast, high-throughput production of improved rabies viral vectors for specific,
efficient and versatile transsynaptic retrograde labeling
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
_id: '11943'
abstract:
- lang: eng
text: Complex wiring between neurons underlies the information-processing network
enabling all brain functions, including cognition and memory. For understanding
how the network is structured, processes information, and changes over time, comprehensive
visualization of the architecture of living brain tissue with its cellular and
molecular components would open up major opportunities. However, electron microscopy
(EM) provides nanometre-scale resolution required for full in-silico
reconstruction1–5, yet is limited to fixed specimens and
static representations. Light microscopy allows live observation, with super-resolution
approaches6–12 facilitating nanoscale visualization, but
comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
We developed an integrated imaging and analysis technology, adapting stimulated
emission depletion (STED) microscopy6,13 in extracellularly
labelled tissue14 for high SNR and near-isotropic resolution.
Centrally, a two-stage deep-learning approach leveraged previously obtained information
on sample structure to drastically reduce photo-burden and enable automated volumetric
reconstruction down to single synapse level. Live reconstruction provides unbiased
analysis of tissue architecture across time in relation to functional activity
and targeted activation, and contextual understanding of molecular labelling.
This adoptable technology will facilitate novel insights into the dynamic functional
architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G. N.
full_name: Grant, Seth G. N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv.
Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.
ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,”
bioRxiv. Cold Spring Harbor Laboratory.
ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.
mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
(n.d.).
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2024-03-27T23:30:20Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor
Laboratory.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory,
doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2024-03-27T23:30:20Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '9329'
abstract:
- lang: eng
text: "Background: To understand information coding in single neurons, it is necessary
to analyze subthreshold synaptic events, action potentials (APs), and their interrelation
in different behavioral states. However, detecting excitatory postsynaptic potentials
(EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of
unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and
variable time course of synaptic events.\r\nNew method: We developed a method
for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure),
which combines concepts of supervised machine learning and optimal Wiener filtering.
Experts were asked to manually score short epochs of data. The algorithm was trained
to obtain the optimal filter coefficients of a Wiener filter and the optimal detection
threshold. Scored and unscored data were then processed with the optimal filter,
and events were detected as peaks above threshold.\r\nResults: We challenged MOD
with EPSP traces in vivo in mice during spatial navigation and EPSC traces in
vitro in slices under conditions of enhanced transmitter release. The area under
the curve (AUC) of the receiver operating characteristics (ROC) curve was, on
average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection
accuracy and efficiency.\r\nComparison with existing methods: When benchmarked
using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution,
and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but
showed comparable (template-fit, deconvolution) or higher (Bayesian) computational
efficacy.\r\nConclusions: MOD may become an important new tool for large-scale,
real-time analysis of synaptic activity."
acknowledged_ssus:
- _id: SSU
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari,
Christoph Lampert, and Federico Stella for critically reading previous manuscript
versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help
with applying the Bayesian detection method to our data. We also thank Florian Marr
for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the
Scientific Service Units of IST Austria for efficient support.
article_number: '109125'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering
method for accurate and efficient detection of subthreshold synaptic events in
vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125'
apa: 'Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A
novel machine-learning optimal-filtering method for accurate and efficient detection
of subthreshold synaptic events in vivo. Journal of Neuroscience Methods.
Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125'
chicago: 'Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD:
A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection
of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods.
Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125.'
ieee: 'X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning
optimal-filtering method for accurate and efficient detection of subthreshold
synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no.
6. Elsevier, 2021.'
ista: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning
optimal-filtering method for accurate and efficient detection of subthreshold
synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.'
mla: 'Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method
for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.”
Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021,
doi:10.1016/j.jneumeth.2021.109125.'
short: X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods
357 (2021).
date_created: 2021-04-18T22:01:39Z
date_published: 2021-03-09T00:00:00Z
date_updated: 2023-08-07T14:36:14Z
day: '09'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.jneumeth.2021.109125
ec_funded: 1
external_id:
isi:
- '000661088500005'
file:
- access_level: open_access
checksum: 2a5800d91b96d08b525e17319dcd5e44
content_type: application/pdf
creator: dernst
date_created: 2021-04-19T08:30:22Z
date_updated: 2021-04-19T08:30:22Z
file_id: '9339'
file_name: 2021_JourNeuroscienceMeth_Zhang.pdf
file_size: 6924738
relation: main_file
success: 1
file_date_updated: 2021-04-19T08:30:22Z
has_accepted_license: '1'
intvolume: ' 357'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Journal of Neuroscience Methods
publication_identifier:
eissn:
- 1872-678X
issn:
- 0165-0270
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'MOD: A novel machine-learning optimal-filtering method for accurate and efficient
detection of subthreshold synaptic events in vivo'
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 357
year: '2021'
...
---
_id: '9778'
abstract:
- lang: eng
text: The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit.
Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this
synaptic connection. It is widely believed that mossy fiber PTP is an entirely
presynaptic phenomenon, implying that PTP induction is input-specific, and requires
neither activity of multiple inputs nor stimulation of postsynaptic neurons. To
directly test cooperativity and associativity, we made paired recordings between
single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain
slices. By stimulating non-overlapping mossy fiber inputs converging onto single
CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly,
mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only
minimal PTP after combined pre- and postsynaptic high-frequency stimulation with
intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic
spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP
is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels,
group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde
vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire
of synaptic computations, implementing a brake on mossy fiber detonation and a
“smart teacher” function of hippocampal mossy fiber synapses.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically
reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois
Schlögl for help with analysis, Florian Marr for excellent technical assistance
and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller
for manuscript editing, and the Scientific Service Units of IST Austria for support.
This project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program (grant agreement No
692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27,
Wittgenstein award), both to P.J.
article_number: '2912'
article_processing_charge: No
article_type: original
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term
plasticity in hippocampal mossy fiber synapses. Nature Communications.
2021;12(1). doi:10.1038/s41467-021-23153-5
apa: Vandael, D. H., Okamoto, Y., & Jonas, P. M. (2021). Transsynaptic modulation
of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature
Communications. Springer. https://doi.org/10.1038/s41467-021-23153-5
chicago: Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation
of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature
Communications. Springer, 2021. https://doi.org/10.1038/s41467-021-23153-5.
ieee: D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic
short-term plasticity in hippocampal mossy fiber synapses,” Nature Communications,
vol. 12, no. 1. Springer, 2021.
ista: Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic
short-term plasticity in hippocampal mossy fiber synapses. Nature Communications.
12(1), 2912.
mla: Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term
Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications,
vol. 12, no. 1, 2912, Springer, 2021, doi:10.1038/s41467-021-23153-5.
short: D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).
date_created: 2021-08-06T07:22:55Z
date_published: 2021-05-18T00:00:00Z
date_updated: 2023-08-10T14:16:16Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-021-23153-5
ec_funded: 1
external_id:
isi:
- '000655481800014'
file:
- access_level: open_access
checksum: 6036a8cdae95e1707c2a04d54e325ff4
content_type: application/pdf
creator: kschuh
date_created: 2021-12-17T11:34:50Z
date_updated: 2021-12-17T11:34:50Z
file_id: '10563'
file_name: 2021_NatureCommunications_Vandael.pdf
file_size: 3108845
relation: main_file
success: 1
file_date_updated: 2021-12-17T11:34:50Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- general physics and astronomy
- general biochemistry
- genetics and molecular biology
- general chemistry
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/
scopus_import: '1'
status: public
title: Transsynaptic modulation of presynaptic short-term plasticity in hippocampal
mossy fiber synapses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '9438'
abstract:
- lang: eng
text: Rigorous investigation of synaptic transmission requires analysis of unitary
synaptic events by simultaneous recording from presynaptic terminals and postsynaptic
target neurons. However, this has been achieved at only a limited number of model
synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical
presynaptic terminals have been largely inaccessible to direct presynaptic recording,
due to their small size. Here, we describe a protocol for improved subcellular
patch-clamp recording in rat and mouse brain slices, with the synapse in a largely
intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc
morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals
are stimulated minimally invasively in the bouton-attached configuration, in which
the cytoplasmic content remains unperturbed, or in the whole-bouton configuration,
in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic
recordings can be integrated with biocytin labeling and morphological analysis,
allowing correlative investigation of synapse structure and function. Paired recordings
can be obtained from mossy fiber terminals in slices from both rats and mice,
implying applicability to genetically modified synapses. Paired recordings can
also be performed together with axon tract stimulation or optogenetic activation,
allowing comparison of unitary and compound synaptic events in the same target
cell. Finally, paired recordings can be combined with spontaneous event analysis,
permitting collection of miniature events generated at a single identified synapse.
In conclusion, the subcellular patch-clamp techniques detailed here should facilitate
analysis of biophysics, plasticity and circuit function of cortical synapses in
the mammalian central nervous system.
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful
to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction,
E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST
Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Benjamin
full_name: Suter, Benjamin
id: 4952F31E-F248-11E8-B48F-1D18A9856A87
last_name: Suter
orcid: 0000-0002-9885-6936
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
pre- and postsynaptic recording at cortical synapses. Nature Protocols.
2021;16(6):2947–2967. doi:10.1038/s41596-021-00526-0
apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter,
B., & Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton
stimulation and simultaneous pre- and postsynaptic recording at cortical synapses.
Nature Protocols. Springer Nature. https://doi.org/10.1038/s41596-021-00526-0
chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas
Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques
for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording
at Cortical Synapses.” Nature Protocols. Springer Nature, 2021. https://doi.org/10.1038/s41596-021-00526-0.
ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter,
and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation
and simultaneous pre- and postsynaptic recording at cortical synapses,” Nature
Protocols, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.
ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and
simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols.
16(6), 2947–2967.
mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton
Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.”
Nature Protocols, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967,
doi:10.1038/s41596-021-00526-0.
short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter,
P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.
date_created: 2021-05-30T22:01:24Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2023-08-10T22:30:51Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41596-021-00526-0
ec_funded: 1
external_id:
isi:
- '000650528700003'
pmid:
- '33990799'
file:
- access_level: open_access
checksum: 7eb580abd8893cdb0b410cf41bc8c263
content_type: application/pdf
creator: cziletti
date_created: 2021-07-08T12:27:55Z
date_updated: 2021-12-02T23:30:05Z
embargo: 2021-12-01
file_id: '9639'
file_name: VandaeletalAuthorVersion2021.pdf
file_size: 38574802
relation: main_file
file_date_updated: 2021-12-02T23:30:05Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Submitted Version
page: 2947–2967
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00739
name: Structural plasticity at mossy fiber-CA3 synapses
publication: Nature Protocols
publication_identifier:
eissn:
- '17502799'
issn:
- '17542189'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
pre- and postsynaptic recording at cortical synapses
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 16
year: '2021'
...
---
_id: '10816'
abstract:
- lang: eng
text: Pattern separation is a fundamental brain computation that converts small
differences in input patterns into large differences in output patterns. Several
synaptic mechanisms of pattern separation have been proposed, including code expansion,
inhibition and plasticity; however, which of these mechanisms play a role in the
entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation
circuit, remains unclear. Here we show that a biologically realistic, full-scale
EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive
inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator.
Both external gamma-modulated inhibition and internal lateral inhibition mediated
by PV+-INs substantially contributed to pattern separation. Both local connectivity
and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness.
Similarly, mossy fiber synapses with conditional detonator properties contributed
to pattern separation. By contrast, perforant path synapses with Hebbian synaptic
plasticity and direct EC–CA3 connection shifted the network towards pattern completion.
Our results demonstrate that the specific properties of cells and synapses optimize
higher-order computations in biological networks and might be useful to improve
the deep learning capabilities of technical networks.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and
T. Vogels for critically reading earlier versions of the manuscript. We are grateful
to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller
for manuscript editing, and the Scientific Service Units of IST Austria for efficient
support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder
for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished
data. This project received funding from the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (grant agreement
no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z
312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.).
article_processing_charge: No
article_type: original
author:
- first_name: José
full_name: Guzmán, José
id: 30CC5506-F248-11E8-B48F-1D18A9856A87
last_name: Guzmán
orcid: 0000-0003-2209-5242
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: 'Claudia '
full_name: 'Espinoza Martinez, Claudia '
id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
last_name: Espinoza Martinez
orcid: 0000-0003-4710-2082
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Benjamin
full_name: Suter, Benjamin
id: 4952F31E-F248-11E8-B48F-1D18A9856A87
last_name: Suter
orcid: 0000-0002-9885-6936
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity
rules and synaptic properties shape the efficacy of pattern separation in the
entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science.
2021;1(12):830-842. doi:10.1038/s43588-021-00157-1
apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &
Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the
efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.
Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-021-00157-1
chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang,
Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties
Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network.” Nature Computational Science. Springer Nature, 2021. https://doi.org/10.1038/s43588-021-00157-1.
ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M.
Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern
separation in the entorhinal cortex–dentate gyrus–CA3 network,” Nature Computational
Science, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021.
ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021.
How connectivity rules and synaptic properties shape the efficacy of pattern separation
in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science.
1(12), 830–842.
mla: Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape
the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network.” Nature Computational Science, vol. 1, no. 12, Springer Nature,
2021, pp. 830–42, doi:10.1038/s43588-021-00157-1.
short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas,
Nature Computational Science 1 (2021) 830–842.
date_created: 2022-03-04T08:32:36Z
date_published: 2021-12-16T00:00:00Z
date_updated: 2023-08-10T22:30:10Z
day: '16'
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department:
- _id: PeJo
doi: 10.1038/s43588-021-00157-1
ec_funded: 1
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page: 830-842
project:
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Nature Computational Science
publication_identifier:
issn:
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publication_status: published
publisher: Springer Nature
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related_material:
link:
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url: https://ista.ac.at/en/news/spot-the-difference/
record:
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relation: software
status: public
scopus_import: '1'
status: public
title: How connectivity rules and synaptic properties shape the efficacy of pattern
separation in the entorhinal cortex–dentate gyrus–CA3 network
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2021'
...
---
_id: '10110'
abstract:
- lang: eng
text: Pattern separation is a fundamental brain computation that converts small
differences in input patterns into large differences in output patterns. Several
synaptic mechanisms of pattern separation have been proposed, including code expansion,
inhibition and plasticity; however, which of these mechanisms play a role in the
entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation
circuit, remains unclear. Here we show that a biologically realistic, full-scale
EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive
inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator.
Both external gamma-modulated inhibition and internal lateral inhibition mediated
by PV+-INs substantially contributed to pattern separation. Both local connectivity
and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness.
Similarly, mossy fiber synapses with conditional detonator properties contributed
to pattern separation. By contrast, perforant path synapses with Hebbian synaptic
plasticity and direct EC–CA3 connection shifted the network towards pattern completion.
Our results demonstrate that the specific properties of cells and synapses optimize
higher-order computations in biological networks and might be useful to improve
the deep learning capabilities of technical networks.
author:
- first_name: José
full_name: Guzmán, José
id: 30CC5506-F248-11E8-B48F-1D18A9856A87
last_name: Guzmán
orcid: 0000-0003-2209-5242
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: 'Claudia '
full_name: 'Espinoza Martinez, Claudia '
id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
last_name: Espinoza Martinez
orcid: 0000-0003-4710-2082
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Benjamin
full_name: Suter, Benjamin
id: 4952F31E-F248-11E8-B48F-1D18A9856A87
last_name: Suter
orcid: 0000-0002-9885-6936
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity
rules and synaptic properties shape the efficacy of pattern separation in the
entorhinal cortex–dentate gyrus–CA3 network. 2021. doi:10.15479/AT:ISTA:10110
apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &
Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the
efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.
IST Austria. https://doi.org/10.15479/AT:ISTA:10110
chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang,
Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties
Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network.” IST Austria, 2021. https://doi.org/10.15479/AT:ISTA:10110.
ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M.
Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern
separation in the entorhinal cortex–dentate gyrus–CA3 network.” IST Austria, 2021.
ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021.
How connectivity rules and synaptic properties shape the efficacy of pattern separation
in the entorhinal cortex–dentate gyrus–CA3 network, IST Austria, 10.15479/AT:ISTA:10110.
mla: Guzmán, José, et al. How Connectivity Rules and Synaptic Properties Shape
the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network. IST Austria, 2021, doi:10.15479/AT:ISTA:10110.
short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas,
(2021).
date_created: 2021-10-08T06:44:22Z
date_published: 2021-12-16T00:00:00Z
date_updated: 2024-03-27T23:30:11Z
day: '16'
ddc:
- '005'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.15479/AT:ISTA:10110
file:
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creator: cchlebak
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relation: main_file
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has_accepted_license: '1'
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publisher: IST Austria
related_material:
link:
- description: News on IST Webpage
relation: press_release
url: https://ist.ac.at/en/news/spot-the-difference/
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status: public
status: public
title: How connectivity rules and synaptic properties shape the efficacy of pattern
separation in the entorhinal cortex–dentate gyrus–CA3 network
tmp:
legal_code_url: https://www.gnu.org/licenses/gpl-3.0.en.html
name: GNU General Public License 3.0
short: GPL 3.0
type: software
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_id: '9437'
abstract:
- lang: eng
text: The synaptic connection from medial habenula (MHb) to interpeduncular nucleus
(IPN) is critical for emotion-related behaviors and uniquely expresses R-type
Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel
tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates
or inhibits transmitter release from MHb terminals depending on the IPN subnucleus,
but the role of KCTDs is unknown. We therefore examined the localization and function
of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells
that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3
currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3
co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional
modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase
of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3
with KCTDs therefore scales synaptic strength independent of GBR activation.
acknowledgement: We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST
antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for
kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided
by Tsutomu Tanabe. This project has received funding from the European Research
Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020
research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto,
no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385
to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard
Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.
article_number: e68274
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Diego
full_name: Fernández-Fernández, Diego
last_name: Fernández-Fernández
- first_name: Thorsten
full_name: Fritzius, Thorsten
last_name: Fritzius
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Hüseyin C
full_name: Önal, Hüseyin C
id: 4659D740-F248-11E8-B48F-1D18A9856A87
last_name: Önal
orcid: 0000-0002-2771-2011
- first_name: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Martin
full_name: Gassmann, Martin
last_name: Gassmann
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Akos
full_name: Kulik, Akos
last_name: Kulik
- first_name: Bernhard
full_name: Bettler, Bernhard
last_name: Bettler
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
citation:
ama: Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary
subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife.
2021;10. doi:10.7554/ELIFE.68274
apa: Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst,
D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits
modulate Cav2.3-mediated release from medial habenula terminals. ELife.
eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274
chicago: Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten
Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber,
et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from
Medial Habenula Terminals.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274.
ieee: P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated
release from medial habenula terminals,” eLife, vol. 10. eLife Sciences
Publications, 2021.
ista: Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D,
Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B,
Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate
Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.
mla: Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated
Release from Medial Habenula Terminals.” ELife, vol. 10, e68274, eLife
Sciences Publications, 2021, doi:10.7554/ELIFE.68274.
short: P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst,
H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B.
Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).
date_created: 2021-05-30T22:01:23Z
date_published: 2021-04-29T00:00:00Z
date_updated: 2024-03-27T23:30:30Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
isi:
- '000651761700001'
file:
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checksum: 6ebcb79999f889766f7cd79ee134ad28
content_type: application/pdf
creator: cziletti
date_created: 2021-05-31T09:43:09Z
date_updated: 2021-05-31T09:43:09Z
file_id: '9440'
file_name: 2021_eLife_Bhandari.pdf
file_size: 8174719
relation: main_file
success: 1
file_date_updated: 2021-05-31T09:43:09Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://doi.org/10.1101/2020.04.16.045112
record:
- id: '9562'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial
habenula terminals
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '8001'
abstract:
- lang: eng
text: Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent
short-term memory. Although PTP has a uniquely large magnitude at hippocampal
mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced
by natural activity and whether its lifetime is sufficient to support short-term
memory. We combined in vivo recordings from granule cells (GCs), in vitro paired
recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash
and freeze” electron microscopy. PTP was induced at single synapses and showed
a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly
generated by enlargement of the readily releasable pool of synaptic vesicles,
allowing multiplicative interaction with other plasticity forms. PTP was associated
with an increase in the docked vesicle pool, suggesting formation of structural
“pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation,
enabling prolonged information storage in the hippocampal network.
acknowledged_ssus:
- _id: SSU
acknowledgement: This project received funding from the European Research Council
(ERC) under the European Union Horizon 2020 Research and Innovation Program (grant
agreement 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung
( Z 312-B27 , Wittgenstein award to P.J. and V 739-B27 to C.B.-M.). We thank Drs.
Jozsef Csicsvari, Jose Guzman, Erwin Neher, and Ryuichi Shigemoto for commenting
on earlier versions of the manuscript. We are grateful to Walter Kaufmann, Daniel
Gütl, and Vanessa Zheden for EM training; Alois Schlögl for programming; Florian
Marr for excellent technical assistance and cell reconstruction; Christina Altmutter
for technical help; Eleftheria Kralli-Beller for manuscript editing; Taija Makinen
for providing the Prox1-CreERT2 mouse line; and the Scientific Service Units of
IST Austria for support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. Short-term plasticity at hippocampal
mossy fiber synapses is induced by natural activity patterns and associated with
vesicle pool engram formation. Neuron. 2020;107(3):509-521. doi:10.1016/j.neuron.2020.05.013
apa: Vandael, D. H., Borges Merjane, C., Zhang, X., & Jonas, P. M. (2020). Short-term
plasticity at hippocampal mossy fiber synapses is induced by natural activity
patterns and associated with vesicle pool engram formation. Neuron. Elsevier.
https://doi.org/10.1016/j.neuron.2020.05.013
chicago: Vandael, David H, Carolina Borges Merjane, Xiaomin Zhang, and Peter M Jonas.
“Short-Term Plasticity at Hippocampal Mossy Fiber Synapses Is Induced by Natural
Activity Patterns and Associated with Vesicle Pool Engram Formation.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.05.013.
ieee: D. H. Vandael, C. Borges Merjane, X. Zhang, and P. M. Jonas, “Short-term plasticity
at hippocampal mossy fiber synapses is induced by natural activity patterns and
associated with vesicle pool engram formation,” Neuron, vol. 107, no. 3.
Elsevier, pp. 509–521, 2020.
ista: Vandael DH, Borges Merjane C, Zhang X, Jonas PM. 2020. Short-term plasticity
at hippocampal mossy fiber synapses is induced by natural activity patterns and
associated with vesicle pool engram formation. Neuron. 107(3), 509–521.
mla: Vandael, David H., et al. “Short-Term Plasticity at Hippocampal Mossy Fiber
Synapses Is Induced by Natural Activity Patterns and Associated with Vesicle Pool
Engram Formation.” Neuron, vol. 107, no. 3, Elsevier, 2020, pp. 509–21,
doi:10.1016/j.neuron.2020.05.013.
short: D.H. Vandael, C. Borges Merjane, X. Zhang, P.M. Jonas, Neuron 107 (2020)
509–521.
date_created: 2020-06-22T13:29:05Z
date_published: 2020-08-05T00:00:00Z
date_updated: 2023-08-22T07:45:25Z
day: '05'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2020.05.013
ec_funded: 1
external_id:
isi:
- '000556135600004'
pmid:
- '32492366'
file:
- access_level: open_access
checksum: 4030b2be0c9625d54694a1e9fb00305e
content_type: application/pdf
creator: dernst
date_created: 2020-11-25T11:23:02Z
date_updated: 2020-11-25T11:23:02Z
file_id: '8811'
file_name: 2020_Neuron_Vandael.pdf
file_size: 4390833
relation: main_file
success: 1
file_date_updated: 2020-11-25T11:23:02Z
has_accepted_license: '1'
intvolume: ' 107'
isi: 1
issue: '3'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 509-521
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00739
name: Structural plasticity at mossy fiber-CA3 synapses
publication: Neuron
publication_identifier:
eissn:
- '10974199'
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/possible-physical-trace-of-short-term-memory-found/
scopus_import: '1'
status: public
title: Short-term plasticity at hippocampal mossy fiber synapses is induced by natural
activity patterns and associated with vesicle pool engram formation
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '8261'
abstract:
- lang: eng
text: Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal
CA3 region, but how they process spatial information remains enigmatic. To examine
the role of GCs in spatial coding, we measured excitatory postsynaptic potentials
(EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt.
Intracellular recording from morphologically identified GCs revealed that most
cells were active, but activity level varied over a wide range. Whereas only ∼5%
of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus,
the GC population broadly encodes spatial information, but only a subset relays
this information to the CA3 network. Fourier analysis indicated that GCs received
conjunctive place-grid-like synaptic input, suggesting code conversion in single
neurons. GC firing was correlated with dendritic complexity and intrinsic excitability,
but not extrinsic excitatory input or dendritic cable properties. Thus, functional
maturation may control input-output transformation and spatial code conversion.
acknowledged_ssus:
- _id: M-Shop
- _id: ScienComp
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award, P.J.). We thank Gyorgy Buzsáki, Jozsef Csicsvari,
Juan Ramirez Villegas, and Federico Stella for commenting on earlier versions of
this manuscript. We also thank Katie Bittner, Michael Brecht, Albert Lee, Jeffery
Magee, and Alejandro Pernía-Andrade for sharing expertise in in vivo patch-clamp
recording. We are grateful to Florian Marr for cell labeling, cell reconstruction,
and technical assistance; Ben Suter for helpful discussions; Christina Altmutter
for technical support; Eleftheria Kralli-Beller for manuscript editing; and Todor
Asenov (Machine Shop) for device construction. We also thank the Scientific Service
Units (SSUs) of IST Austria (Machine Shop, Scientific Computing, and Preclinical
Facility) for efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Zhang X, Schlögl A, Jonas PM. Selective routing of spatial information flow
from input to output in hippocampal granule cells. Neuron. 2020;107(6):1212-1225.
doi:10.1016/j.neuron.2020.07.006
apa: Zhang, X., Schlögl, A., & Jonas, P. M. (2020). Selective routing of spatial
information flow from input to output in hippocampal granule cells. Neuron.
Elsevier. https://doi.org/10.1016/j.neuron.2020.07.006
chicago: Zhang, Xiaomin, Alois Schlögl, and Peter M Jonas. “Selective Routing of
Spatial Information Flow from Input to Output in Hippocampal Granule Cells.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.07.006.
ieee: X. Zhang, A. Schlögl, and P. M. Jonas, “Selective routing of spatial information
flow from input to output in hippocampal granule cells,” Neuron, vol. 107,
no. 6. Elsevier, pp. 1212–1225, 2020.
ista: Zhang X, Schlögl A, Jonas PM. 2020. Selective routing of spatial information
flow from input to output in hippocampal granule cells. Neuron. 107(6), 1212–1225.
mla: Zhang, Xiaomin, et al. “Selective Routing of Spatial Information Flow from
Input to Output in Hippocampal Granule Cells.” Neuron, vol. 107, no. 6,
Elsevier, 2020, pp. 1212–25, doi:10.1016/j.neuron.2020.07.006.
short: X. Zhang, A. Schlögl, P.M. Jonas, Neuron 107 (2020) 1212–1225.
date_created: 2020-08-14T09:36:05Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2023-08-22T08:30:55Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.neuron.2020.07.006
ec_funded: 1
external_id:
isi:
- '000579698700009'
pmid:
- '32763145'
file:
- access_level: open_access
checksum: 44a5960fc083a4cb3488d22224859fdc
content_type: application/pdf
creator: dernst
date_created: 2020-12-04T09:29:21Z
date_updated: 2020-12-04T09:29:21Z
file_id: '8920'
file_name: 2020_Neuron_Zhang.pdf
file_size: 3011120
relation: main_file
success: 1
file_date_updated: 2020-12-04T09:29:21Z
has_accepted_license: '1'
intvolume: ' 107'
isi: 1
issue: '6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1212-1225
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/the-bouncer-in-the-brain/
status: public
title: Selective routing of spatial information flow from input to output in hippocampal
granule cells
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 107
year: '2020'
...
---
_id: '7473'
abstract:
- lang: eng
text: How structural and functional properties of synapses relate to each other
is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms
of synaptic transmission, and electron microscopy (EM) has provided insight into
morphological properties of synapses. Here we describe an enhanced method for
functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure
freezing. We demonstrate that the improved method can be applied to intact networks
in acute brain slices and organotypic slice cultures from mice. As a proof of
concept, we probed vesicle pool changes during synaptic transmission at the hippocampal
mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked
vesicle pool and the functionally defined readily releasable pool and provide
evidence of fast endocytosis at this synapse. Functional EM with acute slices
and slice cultures has the potential to reveal the structural and functional mechanisms
of transmission in intact, genetically perturbed, and disease-affected synapses.
acknowledgement: This project has received funding from the European Research Council
(ERC) and European Commission (EC), under the European Union’s Horizon 2020 research
and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie
708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27
Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto
for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa
Zheden for extensive EM training, advice, and experimental assistance; Benjamin
Suter for substantial help with light stimulation, ImageJ plugins for analysis,
and manuscript editing; Florian Marr and Christina Altmutter for technical support;
Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger
(Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing
the Prox1-CreERT2 mouse line.
article_processing_charge: No
article_type: original
author:
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and
Freeze”) of identified cortical synapses in acute brain slices. Neuron.
2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022
apa: Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron
microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain
slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022
chicago: Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron
Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain
Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022.
ieee: C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy
(‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron,
vol. 105. Elsevier, pp. 992–1006, 2020.
ista: Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash
and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105,
992–1006.
mla: Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and
Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron,
vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022.
short: C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.
date_created: 2020-02-10T15:59:45Z
date_published: 2020-03-18T00:00:00Z
date_updated: 2024-03-27T23:30:07Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2019.12.022
ec_funded: 1
external_id:
isi:
- '000520854700008'
pmid:
- '31928842'
file:
- access_level: open_access
checksum: 3582664addf26859e86ac5bec3e01416
content_type: application/pdf
creator: dernst
date_created: 2020-11-20T08:58:53Z
date_updated: 2020-11-20T08:58:53Z
file_id: '8778'
file_name: 2020_Neuron_BorgesMerjane.pdf
file_size: 9712957
relation: main_file
success: 1
file_date_updated: 2020-11-20T08:58:53Z
has_accepted_license: '1'
intvolume: ' 105'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 992-1006
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '708497'
name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
mossy fiber synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/
record:
- id: '11196'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Functional electron microscopy (“Flash and Freeze”) of identified cortical
synapses in acute brain slices
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 105
year: '2020'
...
---
_id: '11222'
acknowledgement: This work was supported by the ERC and EU Horizon 2020 (ERC 692692;
MSC-IF 708497) and FWF Z 312-B27 Wittgenstein award; W 1205-B09).
article_number: A3.27
article_processing_charge: No
author:
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: 'Kim O, Borges Merjane C, Jonas PM. Functional analysis of the docked vesicle
pool in hippocampal mossy fiber terminals by electron microscopy. In: Intrinsic
Activity. Vol 7. Austrian Pharmacological Society; 2019. doi:10.25006/ia.7.s1-a3.27'
apa: 'Kim, O., Borges Merjane, C., & Jonas, P. M. (2019). Functional analysis
of the docked vesicle pool in hippocampal mossy fiber terminals by electron microscopy.
In Intrinsic Activity (Vol. 7). Innsbruck, Austria: Austrian Pharmacological
Society. https://doi.org/10.25006/ia.7.s1-a3.27'
chicago: Kim, Olena, Carolina Borges Merjane, and Peter M Jonas. “Functional Analysis
of the Docked Vesicle Pool in Hippocampal Mossy Fiber Terminals by Electron Microscopy.”
In Intrinsic Activity, Vol. 7. Austrian Pharmacological Society, 2019.
https://doi.org/10.25006/ia.7.s1-a3.27.
ieee: O. Kim, C. Borges Merjane, and P. M. Jonas, “Functional analysis of the docked
vesicle pool in hippocampal mossy fiber terminals by electron microscopy,” in
Intrinsic Activity, Innsbruck, Austria, 2019, vol. 7, no. Suppl. 1.
ista: 'Kim O, Borges Merjane C, Jonas PM. 2019. Functional analysis of the docked
vesicle pool in hippocampal mossy fiber terminals by electron microscopy. Intrinsic
Activity. ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological
Society vol. 7, A3.27.'
mla: Kim, Olena, et al. “Functional Analysis of the Docked Vesicle Pool in Hippocampal
Mossy Fiber Terminals by Electron Microscopy.” Intrinsic Activity, vol.
7, no. Suppl. 1, A3.27, Austrian Pharmacological Society, 2019, doi:10.25006/ia.7.s1-a3.27.
short: O. Kim, C. Borges Merjane, P.M. Jonas, in:, Intrinsic Activity, Austrian
Pharmacological Society, 2019.
conference:
end_date: 2019-09-27
location: Innsbruck, Austria
name: 'ANA: Austrian Neuroscience Association ; APHAR: Austrian Pharmacological
Society'
start_date: 2019-09-25
date_created: 2022-04-20T15:06:05Z
date_published: 2019-09-11T00:00:00Z
date_updated: 2024-03-27T23:30:07Z
day: '11'
department:
- _id: PeJo
doi: 10.25006/ia.7.s1-a3.27
ec_funded: 1
intvolume: ' 7'
issue: Suppl. 1
keyword:
- hippocampus
- mossy fibers
- readily releasable pool
- electron microscopy
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.intrinsicactivity.org/2019/7/S1/A3.27/
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '708497'
name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
mossy fiber synapse
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication: Intrinsic Activity
publication_identifier:
issn:
- 2309-8503
publication_status: published
publisher: Austrian Pharmacological Society
quality_controlled: '1'
related_material:
record:
- id: '11196'
relation: dissertation_contains
status: public
status: public
title: Functional analysis of the docked vesicle pool in hippocampal mossy fiber terminals
by electron microscopy
type: conference_abstract
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 7
year: '2019'
...