---
_id: '12212'
abstract:
- lang: eng
text: Alzheimer’s disease (AD) is characterized by a reorganization of brain activity
determining network hyperexcitability and loss of synaptic plasticity. Precisely,
a dysfunction in metabotropic GABAB receptor signalling through G protein-gated
inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated.
Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density,
subcellular distribution, and its association with GABAB receptors in hippocampal
CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested
freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay
(P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic
gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in
spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed
a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but
not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed
a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and
axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3,
was significantly reduced along the neuronal surface of CA1 pyramidal cells and
in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering
was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant
reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model.
Overall, our results provide compelling evidence showing a significant reduction
on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not
GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal
pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the
GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB
signalling via GIRK channels in this AD animal model.
acknowledgement: "We thank Ms. Diane Latawiec for the English revision of the manuscript.
Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta
de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center
at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat
de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako
Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis
work was supported by grants from the Spanish Ministerio de Economía y Competitividad
(BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades
de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL,
Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers
16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio
de Universidades and Universidad de Castilla-La Mancha to AMB."
article_number: '136'
article_processing_charge: No
article_type: original
author:
- first_name: Alejandro
full_name: Martín-Belmonte, Alejandro
last_name: Martín-Belmonte
- first_name: Carolina
full_name: Aguado, Carolina
last_name: Aguado
- first_name: Rocío
full_name: Alfaro-Ruiz, Rocío
last_name: Alfaro-Ruiz
- first_name: Ana Esther
full_name: Moreno-Martínez, Ana Esther
last_name: Moreno-Martínez
- first_name: Luis
full_name: de la Ossa, Luis
last_name: de la Ossa
- first_name: Ester
full_name: Aso, Ester
last_name: Aso
- first_name: Laura
full_name: Gómez-Acero, Laura
last_name: Gómez-Acero
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Francisco
full_name: Ciruela, Francisco
last_name: Ciruela
- first_name: Rafael
full_name: Luján, Rafael
last_name: Luján
citation:
ama: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in
GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice.
Alzheimer’s Research & Therapy. 2022;14. doi:10.1186/s13195-022-01078-5
apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de
la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors
and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s
Research & Therapy. Springer Nature. https://doi.org/10.1186/s13195-022-01078-5
chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther
Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale
Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus
of APP/PS1 Mice.” Alzheimer’s Research & Therapy. Springer Nature,
2022. https://doi.org/10.1186/s13195-022-01078-5.
ieee: A. Martín-Belmonte et al., “Nanoscale alterations in GABAB receptors
and GIRK channel organization on the hippocampus of APP/PS1 mice,” Alzheimer’s
Research & Therapy, vol. 14. Springer Nature, 2022.
ista: Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa
L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale
alterations in GABAB receptors and GIRK channel organization on the hippocampus
of APP/PS1 mice. Alzheimer’s Research & Therapy. 14, 136.
mla: Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors
and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s
Research & Therapy, vol. 14, 136, Springer Nature, 2022, doi:10.1186/s13195-022-01078-5.
short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de
la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján,
Alzheimer’s Research & Therapy 14 (2022).
date_created: 2023-01-16T09:45:51Z
date_published: 2022-09-21T00:00:00Z
date_updated: 2023-08-04T09:23:10Z
day: '21'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1186/s13195-022-01078-5
external_id:
isi:
- '000857985500001'
file:
- access_level: open_access
checksum: 88e49715ad6a1abf0fdb27efd65368dc
content_type: application/pdf
creator: dernst
date_created: 2023-01-27T07:53:18Z
date_updated: 2023-01-27T07:53:18Z
file_id: '12413'
file_name: 2022_AlzheimersResearch_MartinBelmont.pdf
file_size: 11013325
relation: main_file
success: 1
file_date_updated: 2023-01-27T07:53:18Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
keyword:
- Cognitive Neuroscience
- Neurology (clinical)
- Neurology
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: Alzheimer's Research & Therapy
publication_identifier:
issn:
- 1758-9193
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nanoscale alterations in GABAB receptors and GIRK channel organization on the
hippocampus of APP/PS1 mice
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: 14
year: '2022'
...
---
_id: '11333'
abstract:
- lang: eng
text: Adenosine triphosphate (ATP) is the energy source for various biochemical
processes and biomolecular motors in living things. Development of ATP antagonists
and their stimuli-controlled actions offer a novel approach to regulate biological
processes. Herein, we developed azobenzene-based photoswitchable ATP antagonists
for controlling the activity of motor proteins; cytoplasmic and axonemal dyneins.
The new ATP antagonists showed reversible photoswitching of cytoplasmic dynein
activity in an in vitro dynein-microtubule system due to the trans and cis photoisomerization
of their azobenzene segment. Importantly, our ATP antagonists reversibly regulated
the axonemal dynein motor activity for the force generation in a demembranated
model of Chlamydomonas reinhardtii. We found that the trans and cis isomers of
ATP antagonists significantly differ in their affinity to the ATP binding site.
article_number: e202200807
article_processing_charge: No
article_type: original
author:
- first_name: Sampreeth
full_name: Thayyil, Sampreeth
last_name: Thayyil
- first_name: Yukinori
full_name: Nishigami, Yukinori
last_name: Nishigami
- first_name: Muhammad J
full_name: Islam, Muhammad J
id: C94881D2-008F-11EA-8E08-2637E6697425
last_name: Islam
- first_name: P. K.
full_name: Hashim, P. K.
last_name: Hashim
- first_name: Ken'Ya
full_name: Furuta, Ken'Ya
last_name: Furuta
- first_name: Kazuhiro
full_name: Oiwa, Kazuhiro
last_name: Oiwa
- first_name: Jian
full_name: Yu, Jian
last_name: Yu
- first_name: Min
full_name: Yao, Min
last_name: Yao
- first_name: Toshiyuki
full_name: Nakagaki, Toshiyuki
last_name: Nakagaki
- first_name: Nobuyuki
full_name: Tamaoki, Nobuyuki
last_name: Tamaoki
citation:
ama: Thayyil S, Nishigami Y, Islam MJ, et al. Dynamic control of microbial movement
by photoswitchable ATP antagonists. Chemistry - A European Journal. 2022;28(30).
doi:10.1002/chem.202200807
apa: Thayyil, S., Nishigami, Y., Islam, M. J., Hashim, P. K., Furuta, K., Oiwa,
K., … Tamaoki, N. (2022). Dynamic control of microbial movement by photoswitchable
ATP antagonists. Chemistry - A European Journal. Wiley. https://doi.org/10.1002/chem.202200807
chicago: Thayyil, Sampreeth, Yukinori Nishigami, Muhammad J Islam, P. K. Hashim,
Ken’Ya Furuta, Kazuhiro Oiwa, Jian Yu, Min Yao, Toshiyuki Nakagaki, and Nobuyuki
Tamaoki. “Dynamic Control of Microbial Movement by Photoswitchable ATP Antagonists.”
Chemistry - A European Journal. Wiley, 2022. https://doi.org/10.1002/chem.202200807.
ieee: S. Thayyil et al., “Dynamic control of microbial movement by photoswitchable
ATP antagonists,” Chemistry - A European Journal, vol. 28, no. 30. Wiley,
2022.
ista: Thayyil S, Nishigami Y, Islam MJ, Hashim PK, Furuta K, Oiwa K, Yu J, Yao M,
Nakagaki T, Tamaoki N. 2022. Dynamic control of microbial movement by photoswitchable
ATP antagonists. Chemistry - A European Journal. 28(30), e202200807.
mla: Thayyil, Sampreeth, et al. “Dynamic Control of Microbial Movement by Photoswitchable
ATP Antagonists.” Chemistry - A European Journal, vol. 28, no. 30, e202200807,
Wiley, 2022, doi:10.1002/chem.202200807.
short: S. Thayyil, Y. Nishigami, M.J. Islam, P.K. Hashim, K. Furuta, K. Oiwa, J.
Yu, M. Yao, T. Nakagaki, N. Tamaoki, Chemistry - A European Journal 28 (2022).
date_created: 2022-04-24T22:01:44Z
date_published: 2022-05-25T00:00:00Z
date_updated: 2023-10-03T10:58:31Z
day: '25'
department:
- _id: RySh
doi: 10.1002/chem.202200807
external_id:
isi:
- '000781658800001'
pmid:
- '35332959'
intvolume: ' 28'
isi: 1
issue: '30'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1002/chem.202200807
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: Chemistry - A European Journal
publication_identifier:
eissn:
- '15213765'
issn:
- '09476539'
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dynamic control of microbial movement by photoswitchable ATP antagonists
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 28
year: '2022'
...
---
_id: '11393'
abstract:
- lang: eng
text: "AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their
role is\r\nimplicated in complex processes such as learning and memory and various
neurological\r\ndiseases. These receptors are composed of different subunits and
the subunit composition can\r\naffect channel properties, receptor trafficking
and interaction with other associated proteins.\r\nUsing the high sensitivity
SDS-digested freeze-fracture replica labeling (SDS-FRL) for\r\nelectron microscopy
I investigated the number, density, and localization of AMPAR subunits,\r\nGluA1,
GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse\r\nhippocampus.
I have found that the immunogold labeling for all of these subunits in the\r\npostsynaptic
sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare.
The labeling density for the all subunits in the extrasynaptic sites showed a
gradual\r\nincrease from the pyramidal cell soma towards the distal part of stratum
radiatum. The densities\r\nof extrasynaptic GluA1, GluA2 and panAMPA labeling
reached 10-15% of synaptic densities,\r\nwhile the ratio of extrasynaptic labeling
for GluA3 was significantly lower compared than those\r\nfor other subunits. The
labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their\r\ndensities
were higher in the periphery than center of synapses. In contrast, the GluA3-\r\ncontaining
receptors were more centrally localized compared to the GluA1- and GluA2-\r\ncontaining
receptors.\r\nThe hippocampus plays a central role in learning and memory. Contextual
learning has been\r\nshown to require the delivery of AMPA receptors to CA1 synapses
in the dorsal hippocampus.\r\nHowever, proximodistal heterogeneity of this plasticity
and particular contribution of different\r\nAMPA receptor subunits are not fully
understood. By combining inhibitory avoidance task, a\r\nhippocampus-dependent
contextual fear-learning paradigm, with SDS-FRL, I have revealed an\r\nincrease
in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.\r\nThe
intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred\r\npattern.
Furthermore, this synaptic plasticity was evident selectively in stratum radiatum
but\r\nnot stratum oriens, and in the CA1 subregion proximal but not distal to
CA2. These findings\r\nfurther contribute to our understanding of how specific
hippocampal subregions and AMPA\r\nreceptor subunits are involved in physiological
learning.\r\nAlthough the immunolabeling results above shed light on subunit-specific
plasticity in\r\nAMPAR distribution, no tools to visualize and study the subunit
composition at the single\r\nchannel level in situ have been available. Electron
microscopy with conventional immunogold\r\nlabeling approaches has limitations
in the single channel analysis because of the large size of\r\nantibodies and
steric hindrance hampering multiple subunit labeling of single channels. I\r\nmanaged
to develop a new chemical labeling system using a short peptide tag and small\r\nsynthetic
probes, which form specific covalent bond with a cysteine residue in the tag fused
to\r\nproteins of interest (reactive tag system). I additionally made substantial
progress into adapting\r\nthis system for AMPA receptor subunits."
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Marijo
full_name: Jevtic, Marijo
id: 4BE3BC94-F248-11E8-B48F-1D18A9856A87
last_name: Jevtic
citation:
ama: Jevtic M. Contextual fear learning induced changes in AMPA receptor subtypes
along the proximodistal axis in dorsal hippocampus. 2022. doi:10.15479/at:ista:11393
apa: Jevtic, M. (2022). Contextual fear learning induced changes in AMPA receptor
subtypes along the proximodistal axis in dorsal hippocampus. Institute of
Science and Technology Austria. https://doi.org/10.15479/at:ista:11393
chicago: Jevtic, Marijo. “Contextual Fear Learning Induced Changes in AMPA Receptor
Subtypes along the Proximodistal Axis in Dorsal Hippocampus.” Institute of Science
and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11393.
ieee: M. Jevtic, “Contextual fear learning induced changes in AMPA receptor subtypes
along the proximodistal axis in dorsal hippocampus,” Institute of Science and
Technology Austria, 2022.
ista: Jevtic M. 2022. Contextual fear learning induced changes in AMPA receptor
subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science
and Technology Austria.
mla: Jevtic, Marijo. Contextual Fear Learning Induced Changes in AMPA Receptor
Subtypes along the Proximodistal Axis in Dorsal Hippocampus. Institute of
Science and Technology Austria, 2022, doi:10.15479/at:ista:11393.
short: M. Jevtic, Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes
along the Proximodistal Axis in Dorsal Hippocampus, Institute of Science and Technology
Austria, 2022.
date_created: 2022-05-17T08:57:41Z
date_published: 2022-05-16T00:00:00Z
date_updated: 2023-09-07T14:53:44Z
day: '16'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:11393
file:
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creator: cchlebak
date_created: 2022-05-17T09:08:06Z
date_updated: 2023-05-17T22:30:03Z
embargo_to: open_access
file_id: '11395'
file_name: MJ thesis.docx
file_size: 56427603
relation: source_file
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checksum: c1dd20a1aece521b3500607b00e463d6
content_type: application/pdf
creator: cchlebak
date_created: 2022-05-17T12:09:25Z
date_updated: 2023-05-17T22:30:03Z
embargo: 2023-05-16
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file_name: MJ_thesis_PDFA.pdf
file_size: 4351981
relation: main_file
file_date_updated: 2023-05-17T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '108'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7391'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: Contextual fear learning induced changes in AMPA receptor subtypes along the
proximodistal axis in dorsal hippocampus
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '7551'
abstract:
- lang: eng
text: Novelty facilitates formation of memories. The detection of novelty and storage
of contextual memories are both mediated by the hippocampus, yet the mechanisms
that link these two functions remain to be defined. Dentate granule cells (GCs)
of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual
memory. However, their key excitatory inputs from the entorhinal cortex are not
responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here
we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal
mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving
dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally
regulates novelty-induced contextual memory acquisition. Our results show that
ventral MCs activity controls memory formation through an intra-hippocampal interaction
mechanism gated by novelty.
acknowledgement: We thank Peter Jonas and Peter Somogyi for critically reading the
manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the
Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also
thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L.
Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research
Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s
expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst,
and Laura Burnett for technical assistance, as well as Robert Beattie for imaging
assistance. This work was supported by a European Research Council Advanced Grant
694539 to R.S.
article_processing_charge: No
article_type: original
author:
- first_name: Felipe A
full_name: Fredes Tolorza, Felipe A
id: 384825DA-F248-11E8-B48F-1D18A9856A87
last_name: Fredes Tolorza
- first_name: Maria A
full_name: Silva Sifuentes, Maria A
id: 371B3D6E-F248-11E8-B48F-1D18A9856A87
last_name: Silva Sifuentes
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
- first_name: Kenta
full_name: Kobayashi, Kenta
last_name: Kobayashi
- 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: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch
MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual
memory formation. Current Biology. 2021;31(1):P25-38.E5. doi:10.1016/j.cub.2020.09.074
apa: Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi,
K., Jösch, M. A., & Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway
gates novelty-induced contextual memory formation. Current Biology. Elsevier.
https://doi.org/10.1016/j.cub.2020.09.074
chicago: Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner,
Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal
Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology.
Elsevier, 2021. https://doi.org/10.1016/j.cub.2020.09.074.
ieee: F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi,
M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced
contextual memory formation,” Current Biology, vol. 31, no. 1. Elsevier,
p. P25–38.E5, 2021.
ista: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch
MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced
contextual memory formation. Current Biology. 31(1), P25–38.E5.
mla: Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates
Novelty-Induced Contextual Memory Formation.” Current Biology, vol. 31,
no. 1, Elsevier, 2021, p. P25–38.E5, doi:10.1016/j.cub.2020.09.074.
short: F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi,
M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5.
date_created: 2020-02-28T10:56:18Z
date_published: 2021-01-11T00:00:00Z
date_updated: 2023-08-04T10:47:11Z
day: '11'
ddc:
- '570'
department:
- _id: MaJö
- _id: RySh
doi: 10.1016/j.cub.2020.09.074
ec_funded: 1
external_id:
isi:
- '000614361000020'
file:
- access_level: open_access
checksum: b7b9c8bc84a08befce365c675229a7d1
content_type: application/pdf
creator: dernst
date_created: 2020-10-19T13:31:28Z
date_updated: 2020-10-19T13:31:28Z
file_id: '8678'
file_name: 2021_CurrentBiology_Fredes.pdf
file_size: 4915964
relation: main_file
success: 1
file_date_updated: 2020-10-19T13:31:28Z
has_accepted_license: '1'
intvolume: ' 31'
isi: 1
issue: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '01'
oa: 1
oa_version: Published Version
page: P25-38.E5
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'
publication: Current Biology
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/remembering-novelty/
status: public
title: Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory 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: 31
year: '2021'
...
---
_id: '9330'
abstract:
- lang: eng
text: In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium
channels have been linked to synaptic functions and neurological disease. Here
we show that α2δ subunits are essential for the formation and organization of
glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown
model, we demonstrate a failure in presynaptic differentiation evidenced by defective
presynaptic calcium channel clustering and calcium influx, smaller presynaptic
active zones, and a strongly reduced accumulation of presynaptic vesicle-associated
proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling
of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms
as synaptic organizers is highly redundant, as each individual α2δ isoform can
rescue presynaptic calcium channel trafficking and expression of synaptic proteins.
Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can
fully rescue presynaptic synapsin expression but only partially calcium channel
trafficking, suggesting that the regulatory role of α2δ subunits is independent
from its role as a calcium channel subunit. Our findings influence the current
view on excitatory synapse formation. First, our study suggests that postsynaptic
differentiation is secondary to presynaptic differentiation. Second, the dependence
of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation
points for the organization of synapses. Finally, our results suggest that α2δ
subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning
the synaptic active zone with the postsynaptic density.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: "We thank Arnold Schwartz for providing α2δ-1 knockout mice; Ariane
Benedetti, Sabine Baumgartner, Sandra Demetz, and Irene Mahlknecht for technical
support; Nadine Ortner and Andreas Lieb for electrophysiological experiments; the
team of the Electron Microscopy Facility at the Institute of Science and Technology
Austria for technical support related to ultrastructural analysis; Hermann Dietrich
and Anja Beierfuß and her team for animal care; Jutta Engel and Jörg Striessnig
for critical discussions; and Bruno Benedetti and Bernhard Flucher for critical
discussions and reading the manuscript. This study was supported by Austrian Science
Fund Grants P24079, F44060, F44150, and DOC30-B30 (to G.J.O.) and T855 (to M.C.),
European Research Council Grant AdG 694539 (to R.S.), Deutsche Forschungsgemeinschaft\r\nGrant
SFB1348-TP A03 (to M.M.), and Interdisziplinäre Zentrum für Klinische Forschung
Münster Grant Mi3/004/19 (to M.M.). This work is part of the PhD theses of C.L.S.,
S.M.G., and C.A."
article_processing_charge: No
article_type: original
author:
- first_name: Clemens L.
full_name: Schöpf, Clemens L.
last_name: Schöpf
- first_name: Cornelia
full_name: Ablinger, Cornelia
last_name: Ablinger
- first_name: Stefanie M.
full_name: Geisler, Stefanie M.
last_name: Geisler
- first_name: Ruslan I.
full_name: Stanika, Ruslan I.
last_name: Stanika
- first_name: Marta
full_name: Campiglio, Marta
last_name: Campiglio
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Benedikt
full_name: Nimmervoll, Benedikt
last_name: Nimmervoll
- first_name: Bettina
full_name: Schlick, Bettina
last_name: Schlick
- first_name: Johannes
full_name: Brockhaus, Johannes
last_name: Brockhaus
- first_name: Markus
full_name: Missler, Markus
last_name: Missler
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Gerald J.
full_name: Obermair, Gerald J.
last_name: Obermair
citation:
ama: Schöpf CL, Ablinger C, Geisler SM, et al. Presynaptic α2δ subunits are key
organizers of glutamatergic synapses. PNAS. 2021;118(14). doi:10.1073/pnas.1920827118
apa: Schöpf, C. L., Ablinger, C., Geisler, S. M., Stanika, R. I., Campiglio, M.,
Kaufmann, W., … Obermair, G. J. (2021). Presynaptic α2δ subunits are key organizers
of glutamatergic synapses. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1920827118
chicago: Schöpf, Clemens L., Cornelia Ablinger, Stefanie M. Geisler, Ruslan I. Stanika,
Marta Campiglio, Walter Kaufmann, Benedikt Nimmervoll, et al. “Presynaptic Α2δ
Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS. National
Academy of Sciences, 2021. https://doi.org/10.1073/pnas.1920827118.
ieee: C. L. Schöpf et al., “Presynaptic α2δ subunits are key organizers of
glutamatergic synapses,” PNAS, vol. 118, no. 14. National Academy of Sciences,
2021.
ista: Schöpf CL, Ablinger C, Geisler SM, Stanika RI, Campiglio M, Kaufmann W, Nimmervoll
B, Schlick B, Brockhaus J, Missler M, Shigemoto R, Obermair GJ. 2021. Presynaptic
α2δ subunits are key organizers of glutamatergic synapses. PNAS. 118(14).
mla: Schöpf, Clemens L., et al. “Presynaptic Α2δ Subunits Are Key Organizers of
Glutamatergic Synapses.” PNAS, vol. 118, no. 14, National Academy of Sciences,
2021, doi:10.1073/pnas.1920827118.
short: C.L. Schöpf, C. Ablinger, S.M. Geisler, R.I. Stanika, M. Campiglio, W. Kaufmann,
B. Nimmervoll, B. Schlick, J. Brockhaus, M. Missler, R. Shigemoto, G.J. Obermair,
PNAS 118 (2021).
date_created: 2021-04-18T22:01:40Z
date_published: 2021-04-06T00:00:00Z
date_updated: 2023-08-08T13:08:47Z
day: '06'
ddc:
- '570'
department:
- _id: EM-Fac
- _id: RySh
doi: 10.1073/pnas.1920827118
ec_funded: 1
external_id:
isi:
- '000637398300002'
file:
- access_level: open_access
checksum: dd014f68ae9d7d8d8fc4139a24e04506
content_type: application/pdf
creator: dernst
date_created: 2021-04-19T10:10:56Z
date_updated: 2021-04-19T10:10:56Z
file_id: '9340'
file_name: 2021_PNAS_Schoepf.pdf
file_size: 2603911
relation: main_file
success: 1
file_date_updated: 2021-04-19T10:10:56Z
has_accepted_license: '1'
intvolume: ' 118'
isi: 1
issue: '14'
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'
publication: PNAS
publication_identifier:
eissn:
- 1091-6490
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Presynaptic α2δ subunits are key organizers of glutamatergic 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: 118
year: '2021'
...
---
_id: '9641'
abstract:
- lang: eng
text: At the encounter with a novel environment, contextual memory formation is
greatly enhanced, accompanied with increased arousal and active exploration. Although
this phenomenon has been widely observed in animal and human daily life, how the
novelty in the environment is detected and contributes to contextual memory formation
has lately started to be unveiled. The hippocampus has been studied for many decades
for its largely known roles in encoding spatial memory, and a growing body of
evidence indicates a differential involvement of dorsal and ventral hippocampal
divisions in novelty detection. In this brief review article, we discuss the recent
findings of the role of mossy cells in the ventral hippocampal moiety in novelty
detection and put them in perspective with other novelty-related pathways in the
hippocampus. We propose a mechanism for novelty-driven memory acquisition in the
dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate
granule cells. By this projection, the ventral hippocampus sends novelty signals
to the dorsal hippocampus, opening a gate for memory encoding in dentate granule
cells based on information coming from the entorhinal cortex. We conclude that,
contrary to the presently accepted functional independence, the dorsal and ventral
hippocampi cooperate to link the novelty and contextual information, and this
dorso-ventral interaction is crucial for the novelty-dependent memory formation.
acknowledgement: This work was supported by a European Research Council Advanced Grant
694539 to Ryuichi Shigemoto.
article_number: '107486'
article_processing_charge: No
article_type: original
author:
- first_name: Felipe
full_name: Fredes, Felipe
last_name: Fredes
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Fredes F, Shigemoto R. The role of hippocampal mossy cells in novelty detection.
Neurobiology of Learning and Memory. 2021;183. doi:10.1016/j.nlm.2021.107486
apa: Fredes, F., & Shigemoto, R. (2021). The role of hippocampal mossy cells
in novelty detection. Neurobiology of Learning and Memory. Elsevier. https://doi.org/10.1016/j.nlm.2021.107486
chicago: Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells
in Novelty Detection.” Neurobiology of Learning and Memory. Elsevier, 2021.
https://doi.org/10.1016/j.nlm.2021.107486.
ieee: F. Fredes and R. Shigemoto, “The role of hippocampal mossy cells in novelty
detection,” Neurobiology of Learning and Memory, vol. 183. Elsevier, 2021.
ista: Fredes F, Shigemoto R. 2021. The role of hippocampal mossy cells in novelty
detection. Neurobiology of Learning and Memory. 183, 107486.
mla: Fredes, Felipe, and Ryuichi Shigemoto. “The Role of Hippocampal Mossy Cells
in Novelty Detection.” Neurobiology of Learning and Memory, vol. 183, 107486,
Elsevier, 2021, doi:10.1016/j.nlm.2021.107486.
short: F. Fredes, R. Shigemoto, Neurobiology of Learning and Memory 183 (2021).
date_created: 2021-07-11T22:01:16Z
date_published: 2021-06-30T00:00:00Z
date_updated: 2023-08-10T14:10:37Z
day: '30'
ddc:
- '610'
department:
- _id: RySh
doi: 10.1016/j.nlm.2021.107486
ec_funded: 1
external_id:
isi:
- '000677694900004'
pmid:
- '34214666'
file:
- access_level: open_access
checksum: 8e8298a9e8c7df146ad23f32c2a63929
content_type: application/pdf
creator: cziletti
date_created: 2021-07-19T13:46:06Z
date_updated: 2021-07-19T13:46:06Z
file_id: '9694'
file_name: 2021_NeurobLearnMemory_Fredes.pdf
file_size: 1994793
relation: main_file
success: 1
file_date_updated: 2021-07-19T13:46:06Z
has_accepted_license: '1'
intvolume: ' 183'
isi: 1
language:
- iso: eng
month: '06'
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'
publication: Neurobiology of Learning and Memory
publication_identifier:
eissn:
- '10959564'
issn:
- '10747427'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: The role of hippocampal mossy cells in novelty detection
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: 183
year: '2021'
...
---
_id: '10051'
abstract:
- lang: eng
text: 'Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein
of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated
Ca2+ channels (CaV), it is considered to be a central organizer of the topography
of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2
knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate
the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs)
with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway
with high release probability. Disruption of RIM-BP2 lowered release probability
altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics
during high-frequency train stimulation indicated a reduction of SVs with high
release probability but an overall normal size of the readily releasable SV pool
(RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion
was slowed. Ultrastructural analysis by superresolution light and electron microscopy
revealed an impaired topography of presynaptic CaV and a reduction of docked and
membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography
of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for
establishing a high initial release probability as required to reliably signal
sound onset information that we found to be degraded in BCs of RIM-BP2-deficient
mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins
(BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach
to the calyceal endbulb of Held synapse that transmits auditory information at
rates of up to hundreds of Hertz with submillisecond precision we demonstrate
a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking
RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+
influx and abundance of the key priming protein Munc13-1, a reduced rate of SV
replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+
channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This
hampers transmission of sound onset information likely affecting downstream neural
computations such as of sound localization.'
acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (DFG,
German Research Foundation) through the Collaborative Sensory Research Center 1286
[to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940.
We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance;
G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke
for technical support and discussion regarding in vivo experiments. We also thank
Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing
RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody,
and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the
STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments
on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang
and J. Neef for constant support and scientific discussion.
article_processing_charge: No
article_type: original
author:
- first_name: Tanvi
full_name: Butola, Tanvi
last_name: Butola
- first_name: Theocharis
full_name: Alvanos, Theocharis
last_name: Alvanos
- first_name: Anika
full_name: Hintze, Anika
last_name: Hintze
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Carolin
full_name: Wichmann, Carolin
last_name: Wichmann
- first_name: Tobias
full_name: Moser, Tobias
last_name: Moser
citation:
ama: Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca21
channel topography and regulates release probability and vesicle replenishment
at a fast central synapse. Journal of Neuroscience. 2021;41(37):7742-7767.
doi:10.1523/JNEUROSCI.0586-21.2021
apa: Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto,
R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca21 channel
topography and regulates release probability and vesicle replenishment at a fast
central synapse. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.0586-21.2021
chicago: Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David
Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding
Protein 2 Organizes Ca21 Channel Topography and Regulates Release Probability
and Vesicle Replenishment at a Fast Central Synapse.” Journal of Neuroscience.
Society for Neuroscience, 2021. https://doi.org/10.1523/JNEUROSCI.0586-21.2021.
ieee: T. Butola et al., “RIM-binding protein 2 organizes Ca21
channel topography and regulates release probability and vesicle replenishment
at a fast central synapse,” Journal of Neuroscience, vol. 41, no. 37. Society
for Neuroscience, pp. 7742–7767, 2021.
ista: Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R,
Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca21 channel
topography and regulates release probability and vesicle replenishment at a fast
central synapse. Journal of Neuroscience. 41(37), 7742–7767.
mla: Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca21 Channel
Topography and Regulates Release Probability and Vesicle Replenishment at a Fast
Central Synapse.” Journal of Neuroscience, vol. 41, no. 37, Society for
Neuroscience, 2021, pp. 7742–67, doi:10.1523/JNEUROSCI.0586-21.2021.
short: T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto,
C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767.
date_created: 2021-09-27T14:33:13Z
date_published: 2021-09-15T00:00:00Z
date_updated: 2023-08-14T06:56:30Z
day: '15'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.0586-21.2021
external_id:
isi:
- '000752287700005'
pmid:
- '34353898'
file:
- access_level: open_access
checksum: 769ab627c7355a50ccfd445e43a5f351
content_type: application/pdf
creator: dernst
date_created: 2022-05-31T09:10:15Z
date_updated: 2022-05-31T09:10:15Z
file_id: '11423'
file_name: 2021_JourNeuroscience_Butola.pdf
file_size: 11571961
relation: main_file
success: 1
file_date_updated: 2022-05-31T09:10:15Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 7742-7767
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: RIM-binding protein 2 organizes Ca21 channel topography and regulates
release probability and vesicle replenishment at a fast central synapse
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: 41
year: '2021'
...
---
_id: '10403'
abstract:
- lang: eng
text: Synaptic transmission, connectivity, and dendritic morphology mature in parallel
during brain development and are often disrupted in neurodevelopmental disorders.
Yet how these changes influence the neuronal computations necessary for normal
brain function are not well understood. To identify cellular mechanisms underlying
the maturation of synaptic integration in interneurons, we combined patch-clamp
recordings of excitatory inputs in mouse cerebellar stellate cells (SCs), three-dimensional
reconstruction of SC morphology with excitatory synapse location, and biophysical
modeling. We found that postnatal maturation of postsynaptic strength was homogeneously
reduced along the somatodendritic axis, but dendritic integration was always sublinear.
However, dendritic branching increased without changes in synapse density, leading
to a substantial gain in distal inputs. Thus, changes in synapse distribution,
rather than dendrite cable properties, are the dominant mechanism underlying the
maturation of neuronal computation. These mechanisms favor the emergence of a
spatially compartmentalized two-stage integration model promoting location-dependent
integration within dendritic subunits.
acknowledgement: This study was supported by the Centre National de la Recherche Scientifique
and the Agence Nationale de la Recherche (ANR-13-BSV4-00166, to LC and DAD). TA
was supported by fellowships from the Fondation pour la Recherche Medicale and the
Swedish Research Council. We thank Dmitry Ershov from the Image Analysis Hub of
the Institut Pasteur, Elodie Le Monnier, Elena Hollergschwandtner, Vanessa Zheden,
and Corinne Nantet for technical support and Haining Zhong for providing the Venus-tagged
PSD95 mouse line. We would like to thank Alberto Bacci, Ann Lohof, and Nelson Rebola
for comments on the manuscript.
article_number: e65954
article_processing_charge: No
article_type: original
author:
- first_name: Celia
full_name: Biane, Celia
last_name: Biane
- first_name: Florian
full_name: Rückerl, Florian
last_name: Rückerl
- first_name: Therese
full_name: Abrahamsson, Therese
last_name: Abrahamsson
- first_name: Cécile
full_name: Saint-Cloment, Cécile
last_name: Saint-Cloment
- first_name: Jean
full_name: Mariani, Jean
last_name: Mariani
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: David A.
full_name: Digregorio, David A.
last_name: Digregorio
- first_name: Rachel M.
full_name: Sherrard, Rachel M.
last_name: Sherrard
- first_name: Laurence
full_name: Cathala, Laurence
last_name: Cathala
citation:
ama: Biane C, Rückerl F, Abrahamsson T, et al. Developmental emergence of two-stage
nonlinear synaptic integration in cerebellar interneurons. eLife. 2021;10.
doi:10.7554/eLife.65954
apa: Biane, C., Rückerl, F., Abrahamsson, T., Saint-Cloment, C., Mariani, J., Shigemoto,
R., … Cathala, L. (2021). Developmental emergence of two-stage nonlinear synaptic
integration in cerebellar interneurons. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.65954
chicago: Biane, Celia, Florian Rückerl, Therese Abrahamsson, Cécile Saint-Cloment,
Jean Mariani, Ryuichi Shigemoto, David A. Digregorio, Rachel M. Sherrard, and
Laurence Cathala. “Developmental Emergence of Two-Stage Nonlinear Synaptic Integration
in Cerebellar Interneurons.” ELife. eLife Sciences Publications, 2021.
https://doi.org/10.7554/eLife.65954.
ieee: C. Biane et al., “Developmental emergence of two-stage nonlinear synaptic
integration in cerebellar interneurons,” eLife, vol. 10. eLife Sciences
Publications, 2021.
ista: Biane C, Rückerl F, Abrahamsson T, Saint-Cloment C, Mariani J, Shigemoto R,
Digregorio DA, Sherrard RM, Cathala L. 2021. Developmental emergence of two-stage
nonlinear synaptic integration in cerebellar interneurons. eLife. 10, e65954.
mla: Biane, Celia, et al. “Developmental Emergence of Two-Stage Nonlinear Synaptic
Integration in Cerebellar Interneurons.” ELife, vol. 10, e65954, eLife
Sciences Publications, 2021, doi:10.7554/eLife.65954.
short: C. Biane, F. Rückerl, T. Abrahamsson, C. Saint-Cloment, J. Mariani, R. Shigemoto,
D.A. Digregorio, R.M. Sherrard, L. Cathala, ELife 10 (2021).
date_created: 2021-12-05T23:01:40Z
date_published: 2021-11-03T00:00:00Z
date_updated: 2023-08-14T13:12:07Z
day: '03'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.65954
external_id:
isi:
- '000715789500001'
file:
- access_level: open_access
checksum: c7c33c3319428d56e332e22349c50ed3
content_type: application/pdf
creator: cchlebak
date_created: 2021-12-10T08:31:41Z
date_updated: 2021-12-10T08:31:41Z
file_id: '10528'
file_name: 2021_eLife_Biane.pdf
file_size: 13131322
relation: main_file
success: 1
file_date_updated: 2021-12-10T08:31:41Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Developmental emergence of two-stage nonlinear synaptic integration in cerebellar
interneurons
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: '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:
- access_level: open_access
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: '9562'
abstract:
- lang: eng
text: Left-right asymmetries can be considered a fundamental organizational principle
of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell
synaptic connection shows an input-side dependent asymmetry where the hemispheric
location of the presynaptic CA3 neuron determines the synaptic properties. Left-input
synapses terminating on apical dendrites in stratum radiatum have a higher density
of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1
and smaller areas with less often perforated PSDs. On the other hand, left-input
synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities
than right-input ones. Apical and basal synapses further employ different signaling
pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize
synaptic membrane proteins with high sensitivity and resolution, and has been
used to reveal the asymmetry at the electron microscopic level. However, it requires
time-consuming manual demarcation of the synaptic surface for quantitative measurements.
To facilitate the analysis of replica labeling, I first developed a software named
Darea, which utilizes deep-learning to automatize this demarcation. With Darea
I characterized the synaptic distribution of NMDA and AMPA receptors as well as
the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I
explored the role of GluN2B and its carboxy-terminus in the establishment of input-side
dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B
expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged
to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were
detected. We further discovered a previously unknown functional asymmetry of GluN2A,
which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus
plays a critical role in normal formation of input-side dependent asymmetry.
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
citation:
ama: 'Kleindienst D. 2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor
subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning.
2021. doi:10.15479/at:ista:9562'
apa: 'Kleindienst, D. (2021). 2B or not 2B: Hippocampal asymmetries mediated
by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis
by Deep-Learning. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:9562'
chicago: 'Kleindienst, David. “2B or Not 2B: Hippocampal Asymmetries Mediated by
NMDA Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by
Deep-Learning.” Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:9562.'
ieee: 'D. Kleindienst, “2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor
subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning,”
Institute of Science and Technology Austria, 2021.'
ista: 'Kleindienst D. 2021. 2B or not 2B: Hippocampal asymmetries mediated by NMDA
receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning.
Institute of Science and Technology Austria.'
mla: 'Kleindienst, David. 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA
Receptor Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:9562.'
short: 'D. Kleindienst, 2B or Not 2B: Hippocampal Asymmetries Mediated by NMDA Receptor
Subunit GluN2B C-Terminus and High-Throughput Image Analysis by Deep-Learning,
Institute of Science and Technology Austria, 2021.'
date_created: 2021-06-17T14:10:47Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2023-09-11T12:55:53Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/at:ista:9562
file:
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checksum: 659df5518db495f679cb1df9e9bd1d94
content_type: application/pdf
creator: dkleindienst
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date_updated: 2022-07-02T22:30:04Z
embargo: 2022-07-01
file_id: '9563'
file_name: Thesis.pdf
file_size: 77299142
relation: main_file
- access_level: closed
checksum: 3bcf63a2b19e5b6663be051bea332748
content_type: application/zip
creator: dkleindienst
date_created: 2021-06-17T14:04:30Z
date_updated: 2022-07-02T22:30:04Z
embargo_to: open_access
file_id: '9564'
file_name: Thesis_source.zip
file_size: 369804895
relation: source_file
file_date_updated: 2022-07-02T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '124'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '9756'
relation: part_of_dissertation
status: public
- id: '9437'
relation: part_of_dissertation
status: public
- id: '8532'
relation: part_of_dissertation
status: public
- id: '612'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
title: '2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B
C-terminus and high-throughput image analysis by Deep-Learning'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...