---
_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: 2024-03-28T23:30:31Z
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:
- access_level: open_access
checksum: 659df5518db495f679cb1df9e9bd1d94
content_type: application/pdf
creator: dkleindienst
date_created: 2021-06-17T14:03:14Z
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'
...
---
_id: '9756'
abstract:
- lang: eng
text: High-resolution visualization and quantification of membrane proteins contribute
to the understanding of their functions and the roles they play in physiological
and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica
labeling (SDS-FRL) is a powerful electron microscopy method to study quantitatively
the two-dimensional distribution of transmembrane proteins and their tightly associated
proteins. During treatment with SDS, intracellular organelles and proteins not
anchored to the replica are dissolved, whereas integral membrane proteins captured
and stabilized by carbon/platinum deposition remain on the replica. Their intra-
and extracellular domains become exposed on the surface of the replica, facilitating
the accessibility of antibodies and, therefore, providing higher labeling efficiency
than those obtained with other immunoelectron microscopy techniques. In this chapter,
we describe the protocols of SDS-FRL adapted for mammalian brain samples, and
optimization of the SDS treatment to increase the labeling efficiency for quantification
of Cav2.1, the alpha subunit of P/Q-type voltage-dependent calcium channels utilizing
deep learning algorithms.
acknowledgement: This work was supported by the European Union (European Research
Council Advanced grant no. 694539 and Human Brain Project Ref. 720270 to R. S.)
and the Austrian Academy of Sciences (DOC fellowship to D.K.).
alternative_title:
- Neuromethods
article_processing_charge: No
author:
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Harumi
full_name: Harada, Harumi
id: 2E55CDF2-F248-11E8-B48F-1D18A9856A87
last_name: Harada
orcid: 0000-0001-7429-7896
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: 'Kaufmann W, Kleindienst D, Harada H, Shigemoto R. High-Resolution localization
and quantitation of membrane proteins by SDS-digested freeze-fracture replica
labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain.
Vol 169. Neuromethods. New York: Humana; 2021:267-283. doi:10.1007/978-1-0716-1522-5_19'
apa: 'Kaufmann, W., Kleindienst, D., Harada, H., & Shigemoto, R. (2021). High-Resolution
localization and quantitation of membrane proteins by SDS-digested freeze-fracture
replica labeling (SDS-FRL). In Receptor and Ion Channel Detection in the Brain
(Vol. 169, pp. 267–283). New York: Humana. https://doi.org/10.1007/978-1-0716-1522-5_19'
chicago: 'Kaufmann, Walter, David Kleindienst, Harumi Harada, and Ryuichi Shigemoto.
“High-Resolution Localization and Quantitation of Membrane Proteins by SDS-Digested
Freeze-Fracture Replica Labeling (SDS-FRL).” In Receptor and Ion Channel Detection
in the Brain, 169:267–83. Neuromethods. New York: Humana, 2021. https://doi.org/10.1007/978-1-0716-1522-5_19.'
ieee: 'W. Kaufmann, D. Kleindienst, H. Harada, and R. Shigemoto, “High-Resolution
localization and quantitation of membrane proteins by SDS-digested freeze-fracture
replica labeling (SDS-FRL),” in Receptor and Ion Channel Detection in the
Brain, vol. 169, New York: Humana, 2021, pp. 267–283.'
ista: 'Kaufmann W, Kleindienst D, Harada H, Shigemoto R. 2021.High-Resolution localization
and quantitation of membrane proteins by SDS-digested freeze-fracture replica
labeling (SDS-FRL). In: Receptor and Ion Channel Detection in the Brain. Neuromethods,
vol. 169, 267–283.'
mla: Kaufmann, Walter, et al. “High-Resolution Localization and Quantitation of
Membrane Proteins by SDS-Digested Freeze-Fracture Replica Labeling (SDS-FRL).”
Receptor and Ion Channel Detection in the Brain, vol. 169, Humana, 2021,
pp. 267–83, doi:10.1007/978-1-0716-1522-5_19.
short: W. Kaufmann, D. Kleindienst, H. Harada, R. Shigemoto, in:, Receptor and
Ion Channel Detection in the Brain, Humana, New York, 2021, pp. 267–283.
date_created: 2021-07-30T09:34:56Z
date_published: 2021-07-27T00:00:00Z
date_updated: 2024-03-28T23:30:31Z
day: '27'
ddc:
- '573'
department:
- _id: RySh
- _id: EM-Fac
doi: 10.1007/978-1-0716-1522-5_19
ec_funded: 1
has_accepted_license: '1'
intvolume: ' 169'
keyword:
- 'Freeze-fracture replica: Deep learning'
- Immunogold labeling
- Integral membrane protein
- Electron microscopy
language:
- iso: eng
month: '07'
oa_version: None
page: 267-283
place: New York
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: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)
publication: ' Receptor and Ion Channel Detection in the Brain'
publication_identifier:
eisbn:
- '9781071615225'
isbn:
- '9781071615218'
publication_status: published
publisher: Humana
quality_controlled: '1'
related_material:
record:
- id: '9562'
relation: dissertation_contains
status: public
series_title: Neuromethods
status: public
title: High-Resolution localization and quantitation of membrane proteins by SDS-digested
freeze-fracture replica labeling (SDS-FRL)
type: book_chapter
user_id: D865714E-FA4E-11E9-B85B-F5C5E5697425
volume: 169
year: '2021'
...
---
_id: '7148'
abstract:
- lang: eng
text: In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where
it regulates synapse formation and regeneration, synaptic plasticity, and motor
learning. Delayed cognitive development in humans with GluD2 gene mutations suggests
extracerebellar functions of GluD2. However, extracerebellar expression of GluD2
and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and
protein were widely detected, with relatively high levels observed in the olfactory
glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular
cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal
thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched
for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial
granular cortex, GluD1 and GluD2 were selectively expressed at PSD‐95‐expressing
glutamatergic synapses, and their coexpression on the same synapses was shown
by SDS‐digested freeze‐fracture replica labeling. Biochemically, GluD1 and GluD2
formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral
cortex and hippocampus. We further estimated the relative protein amount by quantitative
immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards
for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount
of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction
prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly
predominant in the cerebellum. Thus, we have determined the relative extracerebellar
expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These
data provide a molecular–anatomical basis for possible competitive and cooperative
interactions of GluD family members at synapses in various brain regions.
acknowledgement: This study was supported by Grants-in-Aid for Scientific Research
to K.K. (18K06813), Y.M. (17K08503, 17H0631319), and K.S. (16H04650) and a grant
for Scientific Research on Innovative Areas to K.S (16H06276) from the Ministry
of Education, Culture, Sports, Science and Technology of Japan (MEXT). We thank
K. Akashi, I. Watanabe-Iida, Y. Suzuki, and H. Azechi for technical assistance and
advice, and H. Uchida for valuable discussions. We thank E. Kushiya,I. Yabe, C.
Ohori, Y. Mochizuki, Y. Ishikawa, and N. Ishimoto for technical assistance in generating
GluD1-KO mice.
article_processing_charge: No
article_type: original
author:
- first_name: Chihiro
full_name: Nakamoto, Chihiro
last_name: Nakamoto
- first_name: Kohtarou
full_name: Konno, Kohtarou
last_name: Konno
- first_name: Taisuke
full_name: Miyazaki, Taisuke
last_name: Miyazaki
- first_name: Ena
full_name: Nakatsukasa, Ena
last_name: Nakatsukasa
- first_name: Rie
full_name: Natsume, Rie
last_name: Natsume
- first_name: Manabu
full_name: Abe, Manabu
last_name: Abe
- first_name: Meiko
full_name: Kawamura, Meiko
last_name: Kawamura
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Miwako
full_name: Yamasaki, Miwako
last_name: Yamasaki
- first_name: Kenji
full_name: Sakimura, Kenji
last_name: Sakimura
- first_name: Masahiko
full_name: Watanabe, Masahiko
last_name: Watanabe
citation:
ama: Nakamoto C, Konno K, Miyazaki T, et al. Expression mapping, quantification,
and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain.
Journal of Comparative Neurology. 2020;528(6):1003-1027. doi:10.1002/cne.24792
apa: Nakamoto, C., Konno, K., Miyazaki, T., Nakatsukasa, E., Natsume, R., Abe, M.,
… Watanabe, M. (2020). Expression mapping, quantification, and complex formation
of GluD1 and GluD2 glutamate receptors in adult mouse brain. Journal of Comparative
Neurology. Wiley. https://doi.org/10.1002/cne.24792
chicago: Nakamoto, Chihiro, Kohtarou Konno, Taisuke Miyazaki, Ena Nakatsukasa, Rie
Natsume, Manabu Abe, Meiko Kawamura, et al. “Expression Mapping, Quantification,
and Complex Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.”
Journal of Comparative Neurology. Wiley, 2020. https://doi.org/10.1002/cne.24792.
ieee: C. Nakamoto et al., “Expression mapping, quantification, and complex
formation of GluD1 and GluD2 glutamate receptors in adult mouse brain,” Journal
of Comparative Neurology, vol. 528, no. 6. Wiley, pp. 1003–1027, 2020.
ista: Nakamoto C, Konno K, Miyazaki T, Nakatsukasa E, Natsume R, Abe M, Kawamura
M, Fukazawa Y, Shigemoto R, Yamasaki M, Sakimura K, Watanabe M. 2020. Expression
mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors
in adult mouse brain. Journal of Comparative Neurology. 528(6), 1003–1027.
mla: Nakamoto, Chihiro, et al. “Expression Mapping, Quantification, and Complex
Formation of GluD1 and GluD2 Glutamate Receptors in Adult Mouse Brain.” Journal
of Comparative Neurology, vol. 528, no. 6, Wiley, 2020, pp. 1003–27, doi:10.1002/cne.24792.
short: C. Nakamoto, K. Konno, T. Miyazaki, E. Nakatsukasa, R. Natsume, M. Abe, M.
Kawamura, Y. Fukazawa, R. Shigemoto, M. Yamasaki, K. Sakimura, M. Watanabe, Journal
of Comparative Neurology 528 (2020) 1003–1027.
date_created: 2019-12-04T16:09:29Z
date_published: 2020-04-01T00:00:00Z
date_updated: 2023-08-17T14:06:50Z
day: '01'
ddc:
- '571'
- '599'
department:
- _id: RySh
doi: 10.1002/cne.24792
external_id:
isi:
- '000496410200001'
pmid:
- '31625608'
has_accepted_license: '1'
intvolume: ' 528'
isi: 1
issue: '6'
language:
- iso: eng
month: '04'
oa_version: None
page: 1003-1027
pmid: 1
publication: Journal of Comparative Neurology
publication_identifier:
eissn:
- 1096-9861
issn:
- 0021-9967
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Expression mapping, quantification, and complex formation of GluD1 and GluD2
glutamate receptors in adult mouse brain
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 528
year: '2020'
...
---
_id: '7339'
abstract:
- lang: eng
text: Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin)
dynamically support cell structure and functions. In central presynaptic terminals,
F-actin is expressed along the release edge and reportedly plays diverse functional
roles, but whether axonal MTs extend deep into terminals and play any physiological
role remains controversial. At the calyx of Held in rats of either sex, confocal
and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal
swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological
analysis demonstrated that depolymerization of MTs specifically prolonged the
slow-recovery time component of EPSCs from short-term depression induced by a
train of high-frequency stimulation, whereas depolymerization of F-actin specifically
prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic
action potential recordings, depolymerization of MTs or F-actin significantly
impaired the fidelity of high-frequency neurotransmission. We conclude that MTs
and F-actin differentially contribute to slow and fast SV replenishment, thereby
maintaining high-frequency neurotransmission.
article_processing_charge: No
article_type: original
author:
- first_name: Lashmi
full_name: Piriya Ananda Babu, Lashmi
last_name: Piriya Ananda Babu
- first_name: Han Ying
full_name: Wang, Han Ying
last_name: Wang
- first_name: Kohgaku
full_name: Eguchi, Kohgaku
id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
last_name: Eguchi
orcid: 0000-0002-6170-2546
- first_name: Laurent
full_name: Guillaud, Laurent
last_name: Guillaud
- first_name: Tomoyuki
full_name: Takahashi, Tomoyuki
last_name: Takahashi
citation:
ama: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. Microtubule
and actin differentially regulate synaptic vesicle cycling to maintain high-frequency
neurotransmission. Journal of neuroscience. 2020;40(1):131-142. doi:10.1523/JNEUROSCI.1571-19.2019
apa: Piriya Ananda Babu, L., Wang, H. Y., Eguchi, K., Guillaud, L., & Takahashi,
T. (2020). Microtubule and actin differentially regulate synaptic vesicle cycling
to maintain high-frequency neurotransmission. Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1571-19.2019
chicago: Piriya Ananda Babu, Lashmi, Han Ying Wang, Kohgaku Eguchi, Laurent Guillaud,
and Tomoyuki Takahashi. “Microtubule and Actin Differentially Regulate Synaptic
Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal of Neuroscience.
Society for Neuroscience, 2020. https://doi.org/10.1523/JNEUROSCI.1571-19.2019.
ieee: L. Piriya Ananda Babu, H. Y. Wang, K. Eguchi, L. Guillaud, and T. Takahashi,
“Microtubule and actin differentially regulate synaptic vesicle cycling to maintain
high-frequency neurotransmission,” Journal of neuroscience, vol. 40, no.
1. Society for Neuroscience, pp. 131–142, 2020.
ista: Piriya Ananda Babu L, Wang HY, Eguchi K, Guillaud L, Takahashi T. 2020. Microtubule
and actin differentially regulate synaptic vesicle cycling to maintain high-frequency
neurotransmission. Journal of neuroscience. 40(1), 131–142.
mla: Piriya Ananda Babu, Lashmi, et al. “Microtubule and Actin Differentially Regulate
Synaptic Vesicle Cycling to Maintain High-Frequency Neurotransmission.” Journal
of Neuroscience, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 131–42,
doi:10.1523/JNEUROSCI.1571-19.2019.
short: L. Piriya Ananda Babu, H.Y. Wang, K. Eguchi, L. Guillaud, T. Takahashi, Journal
of Neuroscience 40 (2020) 131–142.
date_created: 2020-01-19T23:00:38Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2023-08-17T14:25:23Z
day: '02'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.1571-19.2019
external_id:
isi:
- '000505167600013'
pmid:
- '31767677'
file:
- access_level: open_access
checksum: 92f5e8a47f454fc131fb94cd7f106e60
content_type: application/pdf
creator: dernst
date_created: 2020-01-20T14:44:10Z
date_updated: 2020-07-14T12:47:56Z
file_id: '7345'
file_name: 2020_JourNeuroscience_Piriya.pdf
file_size: 4460781
relation: main_file
file_date_updated: 2020-07-14T12:47:56Z
has_accepted_license: '1'
intvolume: ' 40'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 131-142
pmid: 1
publication: Journal of neuroscience
publication_identifier:
eissn:
- '15292401'
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubule and actin differentially regulate synaptic vesicle cycling to maintain
high-frequency neurotransmission
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: 40
year: '2020'
...
---
_id: '7664'
abstract:
- lang: eng
text: Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control
of network activity and information processing in hippocampal circuits by regulating
neuronal excitability and synaptic transmission. The dysfunction in the dentate
gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement
of GABAB receptors in AD, to determine their subcellular localisation and possible
alteration in granule cells of the DG in a mouse model of AD at 12 months of age,
we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry
at the light microscopic level showed that the regional and cellular expression
pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid
precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice.
High-resolution immunoelectron microscopy revealed a distance-dependent gradient
of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites
in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors
at the neuronal surface of these postsynaptic compartments of granule cells was
significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors,
we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors
were also detected at presynaptic sites in the molecular layer of the DG. We also
found a decrease in plasma membrane GABAB receptors in axon terminals contacting
dendritic spines of granule cells, which was more pronounced in the outer than
in the inner molecular layer. Altogether, our data showing post- and presynaptic
reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated
modulation of excitability and synaptic transmission in granule cells, which may
contribute to the cognitive dysfunctions in the APP/PS1 model of AD
article_number: '2459'
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-Ruíz, Rocío
last_name: Alfaro-Ruíz
- 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: José
full_name: Martínez-Hernández, José
last_name: Martínez-Hernández
- first_name: Alain
full_name: Buisson, Alain
last_name: Buisson
- 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: Rafael
full_name: Luján, Rafael
last_name: Luján
citation:
ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Density of GABAB receptors
is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s
disease. International journal of molecular sciences. 2020;21(7). doi:10.3390/ijms21072459
apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De
La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Density of GABAB receptors
is reduced in granule cells of the hippocampus in a mouse model of Alzheimer’s
disease. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21072459
chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther
Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, Ryuichi
Shigemoto, Yugo Fukazawa, and Rafael Luján. “Density of GABAB Receptors Is Reduced
in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.”
International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21072459.
ieee: A. Martín-Belmonte et al., “Density of GABAB receptors is reduced in
granule cells of the hippocampus in a mouse model of Alzheimer’s disease,” International
journal of molecular sciences, vol. 21, no. 7. MDPI, 2020.
ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa
L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. 2020. Density
of GABAB receptors is reduced in granule cells of the hippocampus in a mouse model
of Alzheimer’s disease. International journal of molecular sciences. 21(7), 2459.
mla: Martín-Belmonte, Alejandro, et al. “Density of GABAB Receptors Is Reduced in
Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease.” International
Journal of Molecular Sciences, vol. 21, no. 7, 2459, MDPI, 2020, doi:10.3390/ijms21072459.
short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De
La Ossa, J. Martínez-Hernández, A. Buisson, R. Shigemoto, Y. Fukazawa, R. Luján,
International Journal of Molecular Sciences 21 (2020).
date_created: 2020-04-19T22:00:55Z
date_published: 2020-04-02T00:00:00Z
date_updated: 2023-08-21T06:13:19Z
day: '02'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3390/ijms21072459
external_id:
isi:
- '000535574200201'
pmid:
- '32252271'
file:
- access_level: open_access
checksum: b9d2f1657d8c4a74b01a62b474d009b0
content_type: application/pdf
creator: dernst
date_created: 2020-04-20T11:43:18Z
date_updated: 2020-07-14T12:48:01Z
file_id: '7669'
file_name: 2020_JournMolecSciences_Martin_Belmonte.pdf
file_size: 2941197
relation: main_file
file_date_updated: 2020-07-14T12:48:01Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '7'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: International journal of molecular sciences
publication_identifier:
eissn:
- '14220067'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Density of GABAB receptors is reduced in granule cells of the hippocampus in
a mouse model of Alzheimer's disease
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: 21
year: '2020'
...
---
_id: '7665'
abstract:
- lang: eng
text: Acute brain slice preparation is a powerful experimental model for investigating
the characteristics of synaptic function in the brain. Although brain tissue is
usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal
damage, exposure to CT causes molecular and architectural changes of synapses.
To address these issues, we investigated ultrastructural and electrophysiological
features of synapses in mouse acute cerebellar slices prepared at ice-cold and
physiological temperature (PT). In the slices prepared at CT, we found significant
spine loss and reconstruction, synaptic vesicle rearrangement and decrease in
synaptic proteins, all of which were not detected in slices prepared at PT. Consistent
with these structural findings, slices prepared at PT showed higher release probability.
Furthermore, preparation at PT allows electrophysiological recording immediately
after slicing resulting in higher detectability of long-term depression (LTD)
after motor learning compared with that at CT. These results indicate substantial
advantages of the slice preparation at PT for investigating synaptic functions
in different physiological conditions.
article_number: '63'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Kohgaku
full_name: Eguchi, Kohgaku
id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
last_name: Eguchi
orcid: 0000-0002-6170-2546
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Elena
full_name: Hollergschwandtner, Elena
id: 3C054040-F248-11E8-B48F-1D18A9856A87
last_name: Hollergschwandtner
- first_name: Makoto
full_name: Itakura, Makoto
last_name: Itakura
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- 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: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Eguchi K, Velicky P, Saeckl E, et al. Advantages of acute brain slices prepared
at physiological temperature in the characterization of synaptic functions. Frontiers
in Cellular Neuroscience. 2020;14. doi:10.3389/fncel.2020.00063
apa: Eguchi, K., Velicky, P., Saeckl, E., Itakura, M., Fukazawa, Y., Danzl, J. G.,
& Shigemoto, R. (2020). Advantages of acute brain slices prepared at physiological
temperature in the characterization of synaptic functions. Frontiers in Cellular
Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2020.00063
chicago: Eguchi, Kohgaku, Philipp Velicky, Elena Saeckl, Makoto Itakura, Yugo Fukazawa,
Johann G Danzl, and Ryuichi Shigemoto. “Advantages of Acute Brain Slices Prepared
at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers
in Cellular Neuroscience. Frontiers Media, 2020. https://doi.org/10.3389/fncel.2020.00063.
ieee: K. Eguchi et al., “Advantages of acute brain slices prepared at physiological
temperature in the characterization of synaptic functions,” Frontiers in Cellular
Neuroscience, vol. 14. Frontiers Media, 2020.
ista: Eguchi K, Velicky P, Saeckl E, Itakura M, Fukazawa Y, Danzl JG, Shigemoto
R. 2020. Advantages of acute brain slices prepared at physiological temperature
in the characterization of synaptic functions. Frontiers in Cellular Neuroscience.
14, 63.
mla: Eguchi, Kohgaku, et al. “Advantages of Acute Brain Slices Prepared at Physiological
Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular
Neuroscience, vol. 14, 63, Frontiers Media, 2020, doi:10.3389/fncel.2020.00063.
short: K. Eguchi, P. Velicky, E. Saeckl, M. Itakura, Y. Fukazawa, J.G. Danzl, R.
Shigemoto, Frontiers in Cellular Neuroscience 14 (2020).
date_created: 2020-04-19T22:00:55Z
date_published: 2020-03-19T00:00:00Z
date_updated: 2023-08-21T06:12:48Z
day: '19'
ddc:
- '570'
department:
- _id: JoDa
- _id: RySh
doi: 10.3389/fncel.2020.00063
ec_funded: 1
external_id:
isi:
- '000525582200001'
file:
- access_level: open_access
checksum: 1c145123c6f8dc3e2e4bd5a66a1ad60e
content_type: application/pdf
creator: dernst
date_created: 2020-04-20T10:59:49Z
date_updated: 2020-07-14T12:48:01Z
file_id: '7668'
file_name: 2020_FrontiersCellularNeurosc_Eguchi.pdf
file_size: 9227283
relation: main_file
file_date_updated: 2020-07-14T12:48:01Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2659CC84-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '793482'
name: 'Ultrastructural analysis of phosphoinositides in nerve terminals: distribution,
dynamics and physiological roles in synaptic transmission'
- _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: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: B67AFEDC-15C9-11EA-A837-991A96BB2854
name: IST Austria Open Access Fund
publication: Frontiers in Cellular Neuroscience
publication_identifier:
issn:
- '16625102'
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: Advantages of acute brain slices prepared at physiological temperature in the
characterization of synaptic functions
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: '2020'
...
---
_id: '7878'
abstract:
- lang: eng
text: Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal
signaling. While their function is well documented in slices, requirements for
their activation in vivo are poorly understood. We examine this question in adult
mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons
(MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes
beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s
and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases
Cai rises associated with locomotion. In vitro studies and freeze-fracture electron
microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by
close association of the two classes of receptors. Altogether our results suggest
that mGluR1s, acting in synergy with iGluRs, potently contribute to processing
cerebellar neuronal signaling under physiological conditions.
article_number: e56839
article_processing_charge: No
article_type: original
author:
- first_name: Jin
full_name: Bao, Jin
last_name: Bao
- first_name: Michael
full_name: Graupner, Michael
last_name: Graupner
- first_name: Guadalupe
full_name: Astorga, Guadalupe
last_name: Astorga
- first_name: Thibault
full_name: Collin, Thibault
last_name: Collin
- first_name: Abdelali
full_name: Jalil, Abdelali
last_name: Jalil
- first_name: Dwi Wahyu
full_name: Indriati, Dwi Wahyu
last_name: Indriati
- first_name: Jonathan
full_name: Bradley, Jonathan
last_name: Bradley
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Isabel
full_name: Llano, Isabel
last_name: Llano
citation:
ama: Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic
glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife.
2020;9. doi:10.7554/eLife.56839
apa: Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W.,
… Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate
receptors in cerebellar molecular layer interneurons in vivo. ELife. eLife
Sciences Publications. https://doi.org/10.7554/eLife.56839
chicago: Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali
Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano.
“Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar
Molecular Layer Interneurons in Vivo.” ELife. eLife Sciences Publications,
2020. https://doi.org/10.7554/eLife.56839.
ieee: J. Bao et al., “Synergism of type 1 metabotropic and ionotropic glutamate
receptors in cerebellar molecular layer interneurons in vivo,” eLife, vol.
9. eLife Sciences Publications, 2020.
ista: Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto
R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors
in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839.
mla: Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate
Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” ELife, vol.
9, e56839, eLife Sciences Publications, 2020, doi:10.7554/eLife.56839.
short: J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley,
R. Shigemoto, I. Llano, ELife 9 (2020).
date_created: 2020-05-24T22:00:58Z
date_published: 2020-05-13T00:00:00Z
date_updated: 2023-08-21T06:26:50Z
day: '13'
ddc:
- '570'
department:
- _id: RySh
doi: 10.7554/eLife.56839
external_id:
isi:
- '000535191600001'
pmid:
- '32401196'
file:
- access_level: open_access
checksum: 8ea99bb6660cc407dbdb00c173b01683
content_type: application/pdf
creator: dernst
date_created: 2020-05-26T09:34:54Z
date_updated: 2020-07-14T12:48:04Z
file_id: '7891'
file_name: 2020_eLife_Bao.pdf
file_size: 4832050
relation: main_file
file_date_updated: 2020-07-14T12:48:04Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar
molecular layer interneurons in vivo
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: 9
year: '2020'
...
---
_id: '7908'
abstract:
- lang: eng
text: Volatile anesthetics are widely used for surgery, but neuronal mechanisms
of anesthesia remain unidentified. At the calyx of Held in brainstem slices from
rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing
the release probability and the number of readily releasable vesicles. In presynaptic
recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated
exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization,
whereas it inhibited exocytosis evoked by a prolonged depolarization via directly
blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic
depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia
is likely mediated by distinct dual mechanisms, depending on input frequencies.
In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane
impaired the fidelity of repetitive spike transmission, more strongly at higher
frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited
monosynaptic corticocortical spike transmission, preferentially at a higher frequency.
We conclude that dual presynaptic mechanisms operate for the anesthetic action
of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass
filtering role in spike transmission at central excitatory synapses.
article_processing_charge: No
article_type: original
author:
- first_name: Han Ying
full_name: Wang, Han Ying
last_name: Wang
- first_name: Kohgaku
full_name: Eguchi, Kohgaku
id: 2B7846DC-F248-11E8-B48F-1D18A9856A87
last_name: Eguchi
orcid: 0000-0002-6170-2546
- first_name: Takayuki
full_name: Yamashita, Takayuki
last_name: Yamashita
- first_name: Tomoyuki
full_name: Takahashi, Tomoyuki
last_name: Takahashi
citation:
ama: Wang HY, Eguchi K, Yamashita T, Takahashi T. Frequency-dependent block of excitatory
neurotransmission by isoflurane via dual presynaptic mechanisms. Journal of
Neuroscience. 2020;40(21):4103-4115. doi:10.1523/JNEUROSCI.2946-19.2020
apa: Wang, H. Y., Eguchi, K., Yamashita, T., & Takahashi, T. (2020). Frequency-dependent
block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms.
Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.2946-19.2020
chicago: Wang, Han Ying, Kohgaku Eguchi, Takayuki Yamashita, and Tomoyuki Takahashi.
“Frequency-Dependent Block of Excitatory Neurotransmission by Isoflurane via Dual
Presynaptic Mechanisms.” Journal of Neuroscience. Society for Neuroscience,
2020. https://doi.org/10.1523/JNEUROSCI.2946-19.2020.
ieee: H. Y. Wang, K. Eguchi, T. Yamashita, and T. Takahashi, “Frequency-dependent
block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms,”
Journal of Neuroscience, vol. 40, no. 21. Society for Neuroscience, pp.
4103–4115, 2020.
ista: Wang HY, Eguchi K, Yamashita T, Takahashi T. 2020. Frequency-dependent block
of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms.
Journal of Neuroscience. 40(21), 4103–4115.
mla: Wang, Han Ying, et al. “Frequency-Dependent Block of Excitatory Neurotransmission
by Isoflurane via Dual Presynaptic Mechanisms.” Journal of Neuroscience,
vol. 40, no. 21, Society for Neuroscience, 2020, pp. 4103–15, doi:10.1523/JNEUROSCI.2946-19.2020.
short: H.Y. Wang, K. Eguchi, T. Yamashita, T. Takahashi, Journal of Neuroscience
40 (2020) 4103–4115.
date_created: 2020-05-31T22:00:48Z
date_published: 2020-05-20T00:00:00Z
date_updated: 2023-08-21T06:31:25Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.2946-19.2020
external_id:
isi:
- '000535694700004'
file:
- access_level: open_access
checksum: 6571607ea9036154b67cc78e848a7f7d
content_type: application/pdf
creator: dernst
date_created: 2020-06-02T09:12:16Z
date_updated: 2020-07-14T12:48:05Z
file_id: '7912'
file_name: 2020_JourNeuroscience_Wang.pdf
file_size: 3817360
relation: main_file
file_date_updated: 2020-07-14T12:48:05Z
has_accepted_license: '1'
intvolume: ' 40'
isi: 1
issue: '21'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 4103-4115
publication: Journal of Neuroscience
publication_identifier:
eissn:
- '15292401'
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Frequency-dependent block of excitatory neurotransmission by isoflurane via
dual presynaptic mechanisms
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: 40
year: '2020'
...
---
_id: '7207'
abstract:
- lang: eng
text: The hippocampus plays key roles in learning and memory and is a main target
of Alzheimer's disease (AD), which causes progressive memory impairments. Despite
numerous investigations about the processes required for the normal hippocampal
functions, the neurotransmitter receptors involved in the synaptic deficits by
which AD disables the hippocampus are not yet characterized. By combining histoblots,
western blots, immunohistochemistry and high‐resolution immunoelectron microscopic
methods for GABAB receptors, this study provides a quantitative description of
the expression and the subcellular localization of GABAB1 in the hippocampus in
a mouse model of AD at 1, 6 and 12 months of age. Western blots and histoblots
showed that the total amount of protein and the laminar expression pattern of
GABAB1 were similar in APP/PS1 mice and in age‐matched wild‐type mice. In contrast,
immunoelectron microscopic techniques showed that the subcellular localization
of GABAB1 subunit did not change significantly in APP/PS1 mice at 1 month of age,
was significantly reduced in the stratum lacunosum‐moleculare of CA1 pyramidal
cells at 6 months of age and significantly reduced at the membrane surface of
CA1 pyramidal cells at 12 months of age. This reduction of plasma membrane GABAB1
was paralleled by a significant increase of the subunit at the intracellular sites.
We further observed a decrease of membrane‐targeted GABAB receptors in axon terminals
contacting CA1 pyramidal cells. Our data demonstrate compartment‐ and age‐dependent
reduction of plasma membrane‐targeted GABAB receptors in the CA1 region of the
hippocampus, suggesting that this decrease might be enough to alter the GABAB‐mediated
synaptic transmission taking place in AD.
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-Ruíz, Rocío
last_name: Alfaro-Ruíz
- 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: José
full_name: Martínez-Hernández, José
last_name: Martínez-Hernández
- first_name: Alain
full_name: Buisson, Alain
last_name: Buisson
- first_name: Simon
full_name: Früh, Simon
last_name: Früh
- 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: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Rafael
full_name: Luján, Rafael
last_name: Luján
citation:
ama: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, et al. Reduction in the neuronal
surface of post and presynaptic GABA>B< receptors in the hippocampus in
a mouse model of Alzheimer’s disease. Brain Pathology. 2020;30(3):554-575.
doi:10.1111/bpa.12802
apa: Martín-Belmonte, A., Aguado, C., Alfaro-Ruíz, R., Moreno-Martínez, A. E., De
La Ossa, L., Martínez-Hernández, J., … Luján, R. (2020). Reduction in the neuronal
surface of post and presynaptic GABA>B< receptors in the hippocampus in
a mouse model of Alzheimer’s disease. Brain Pathology. Wiley. https://doi.org/10.1111/bpa.12802
chicago: Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruíz, Ana Esther
Moreno-Martínez, Luis De La Ossa, José Martínez-Hernández, Alain Buisson, et al.
“Reduction in the Neuronal Surface of Post and Presynaptic GABA>B< Receptors
in the Hippocampus in a Mouse Model of Alzheimer’s Disease.” Brain Pathology.
Wiley, 2020. https://doi.org/10.1111/bpa.12802.
ieee: A. Martín-Belmonte et al., “Reduction in the neuronal surface of post
and presynaptic GABA>B< receptors in the hippocampus in a mouse model
of Alzheimer’s disease,” Brain Pathology, vol. 30, no. 3. Wiley, pp. 554–575,
2020.
ista: Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, De La Ossa
L, Martínez-Hernández J, Buisson A, Früh S, Bettler B, Shigemoto R, Fukazawa Y,
Luján R. 2020. Reduction in the neuronal surface of post and presynaptic GABA>B<
receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathology.
30(3), 554–575.
mla: Martín-Belmonte, Alejandro, et al. “Reduction in the Neuronal Surface of Post
and Presynaptic GABA>B< Receptors in the Hippocampus in a Mouse Model
of Alzheimer’s Disease.” Brain Pathology, vol. 30, no. 3, Wiley, 2020,
pp. 554–75, doi:10.1111/bpa.12802.
short: A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruíz, A.E. Moreno-Martínez, L. De
La Ossa, J. Martínez-Hernández, A. Buisson, S. Früh, B. Bettler, R. Shigemoto,
Y. Fukazawa, R. Luján, Brain Pathology 30 (2020) 554–575.
date_created: 2019-12-22T23:00:43Z
date_published: 2020-05-01T00:00:00Z
date_updated: 2023-09-06T14:48:01Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1111/bpa.12802
ec_funded: 1
external_id:
isi:
- '000502270900001'
pmid:
- '31729777'
file:
- access_level: open_access
checksum: 549cc1b18f638a21d17a939ba5563fa9
content_type: application/pdf
creator: dernst
date_created: 2020-09-22T09:47:19Z
date_updated: 2020-09-22T09:47:19Z
file_id: '8554'
file_name: 2020_BrainPathology_MartinBelmonte.pdf
file_size: 4220935
relation: main_file
success: 1
file_date_updated: 2020-09-22T09:47:19Z
has_accepted_license: '1'
intvolume: ' 30'
isi: 1
issue: '3'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 554-575
pmid: 1
project:
- _id: 25CBA828-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '720270'
name: Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)
- _id: 26436750-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '785907'
name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)
publication: Brain Pathology
publication_identifier:
eissn:
- '17503639'
issn:
- '10156305'
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Reduction in the neuronal surface of post and presynaptic GABA>B< receptors
in the hippocampus in a mouse model of Alzheimer's disease
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 30
year: '2020'
...
---
_id: '7525'
abstract:
- lang: eng
text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure
important for the modulation of emotional memory. It is involved in regulation
of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and
feeding behavior. MHb receives inputs from septal regions and projects exclusively
to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project
to different subnuclei of MHb: the bed nucleus of anterior commissure projects
to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore,
the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively.
Importantly, these projections have unique features of prominent co-release of
different neurotransmitters and requirement of a peculiar type of calcium channel
for release. In general, synaptic neurotransmission requires an activity-dependent
influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels.
The calcium channel family most commonly involved in neurotransmitter release
comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits,
respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or
Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of
the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements.
This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique
mechanisms of glutamate release in this pathway. One potential example of such
uniqueness is the facilitation of release by GABAB receptor (GBR) activation.
Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting
presynaptic calcium channels. MHb shows the highest expression levels of GBR in
the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are
associated with auxiliary subunits, called potassium channel tetramerization domain
containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b
is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression
in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b
may be involved in the unique mechanisms of neurotransmitter release mediated
by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we
first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways
is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482.
We next found that baclofen, a GBR agonist, has facilitatory effects on release
from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on
release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed
exclusively in ventral MHb may have a role in the facilitatory effects of GBR
activation. In a heterologous expression system using HEK cells, we found that
KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold
electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely
in presynaptic active zone in IPN with KCTD12b being present only in rostral/central
but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely
in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements
and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3,
KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating
that they may form complexes regulating vesicle release in rostral IPN. \r\nOn
electrophysiological studies of wild type (WT) mice, we found that paired-pulse
ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT
and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release
probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8
KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO
mice, the mean variance analysis revealed significantly lower release probability
in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional
regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation
in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8
and KCTD12b KO mice, and found the facilitation of release remained in both KO
mice, indicating that the peculiar effects of the GBR activation in this pathway
do not depend on the selective expression of these KCTD subunits in ventral MHb.
However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen
falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and
KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained
potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in
its termination in the absence of KCTD12b. Consistent with these functional findings,
replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or
GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT
mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the
release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn
summary, our study provided new insights into the physiological roles of presynaptic
Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal
circuit. Future studies will be required to identify the exact molecular mechanism
underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals.
It remains to be determined whether the prominent presence of presynaptic KCTDs
at active zone could exert similar neuromodulatory functions in different pathways
of the brain.\r\n"
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
citation:
ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525
apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7525
chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology
Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.
ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula
to interpeduncular nucleus pathway,” Institute of Science and Technology Austria,
2020.
ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial
habenula to interpeduncular nucleus pathway. Institute of Science and Technology
Austria.
mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial
Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology
Austria, 2020, doi:10.15479/AT:ISTA:7525.
short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula
to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria,
2020.
date_created: 2020-02-26T10:56:37Z
date_published: 2020-02-28T00:00:00Z
date_updated: 2023-09-07T13:20:03Z
day: '28'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: RySh
doi: 10.15479/AT:ISTA:7525
file:
- access_level: open_access
checksum: 4589234fdb12b4ad72273b311723a7b4
content_type: application/pdf
creator: pbhandari
date_created: 2020-02-28T08:37:53Z
date_updated: 2021-03-01T23:30:04Z
embargo: 2021-02-28
file_id: '7538'
file_name: Pradeep Bhandari Thesis.pdf
file_size: 9646346
relation: main_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
- access_level: closed
checksum: aa79490553ca0a5c9b6fbcd152e93928
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: pbhandari
date_created: 2020-02-28T08:47:14Z
date_updated: 2021-03-01T23:30:04Z
embargo_to: open_access
file_id: '7539'
file_name: Pradeep Bhandari Thesis.docx
file_size: 35252164
relation: source_file
title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
file_date_updated: 2021-03-01T23:30:04Z
has_accepted_license: '1'
keyword:
- Cav2.3
- medial habenula (MHb)
- interpeduncular nucleus (IPN)
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: '79'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular
nucleus pathway
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8532'
abstract:
- lang: eng
text: The molecular anatomy of synapses defines their characteristics in transmission
and plasticity. Precise measurements of the number and distribution of synaptic
proteins are important for our understanding of synapse heterogeneity within and
between brain regions. Freeze–fracture replica immunogold electron microscopy
enables us to analyze them quantitatively on a two-dimensional membrane surface.
Here, we introduce Darea software, which utilizes deep learning for analysis of
replica images and demonstrate its usefulness for quick measurements of the pre-
and postsynaptic areas, density and distribution of gold particles at synapses
in a reproducible manner. We used Darea for comparing glutamate receptor and calcium
channel distributions between hippocampal CA3-CA1 spine synapses on apical and
basal dendrites, which differ in signaling pathways involved in synaptic plasticity.
We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic
size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA)
receptors with size. Interestingly, AMPA and NMDA receptors are segregated within
postsynaptic sites and negatively correlated in density among both apical and
basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels
show similar densities in apical and basal synapses with distributions consistent
with an exclusion zone model of calcium channel-release site topography.
acknowledgement: "This research was funded by Austrian Academy of Sciences, DOC fellowship
to D.K., European Research\r\nCouncil Advanced Grant 694539 and European Union Human
Brain Project (HBP) SGA2 785907 to R.S.\r\nWe acknowledge Elena Hollergschwandtner
for technical support."
article_number: '6737'
article_processing_charge: No
article_type: original
author:
- first_name: David
full_name: Kleindienst, David
id: 42E121A4-F248-11E8-B48F-1D18A9856A87
last_name: Kleindienst
- first_name: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Matthew J
full_name: Case, Matthew J
id: 44B7CA5A-F248-11E8-B48F-1D18A9856A87
last_name: Case
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 2020;21(18). doi:10.3390/ijms21186737
apa: Kleindienst, D., Montanaro-Punzengruber, J.-C., Bhandari, P., Case, M. J.,
Fukazawa, Y., & Shigemoto, R. (2020). Deep learning-assisted high-throughput
analysis of freeze-fracture replica images applied to glutamate receptors and
calcium channels at hippocampal synapses. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21186737
chicago: Kleindienst, David, Jacqueline-Claire Montanaro-Punzengruber, Pradeep Bhandari,
Matthew J Case, Yugo Fukazawa, and Ryuichi Shigemoto. “Deep Learning-Assisted
High-Throughput Analysis of Freeze-Fracture Replica Images Applied to Glutamate
Receptors and Calcium Channels at Hippocampal Synapses.” International Journal
of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21186737.
ieee: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M. J. Case, Y.
Fukazawa, and R. Shigemoto, “Deep learning-assisted high-throughput analysis of
freeze-fracture replica images applied to glutamate receptors and calcium channels
at hippocampal synapses,” International Journal of Molecular Sciences,
vol. 21, no. 18. MDPI, 2020.
ista: Kleindienst D, Montanaro-Punzengruber J-C, Bhandari P, Case MJ, Fukazawa Y,
Shigemoto R. 2020. Deep learning-assisted high-throughput analysis of freeze-fracture
replica images applied to glutamate receptors and calcium channels at hippocampal
synapses. International Journal of Molecular Sciences. 21(18), 6737.
mla: Kleindienst, David, et al. “Deep Learning-Assisted High-Throughput Analysis
of Freeze-Fracture Replica Images Applied to Glutamate Receptors and Calcium Channels
at Hippocampal Synapses.” International Journal of Molecular Sciences,
vol. 21, no. 18, 6737, MDPI, 2020, doi:10.3390/ijms21186737.
short: D. Kleindienst, J.-C. Montanaro-Punzengruber, P. Bhandari, M.J. Case, Y.
Fukazawa, R. Shigemoto, International Journal of Molecular Sciences 21 (2020).
date_created: 2020-09-20T22:01:35Z
date_published: 2020-09-14T00:00:00Z
date_updated: 2024-03-28T23:30:31Z
day: '14'
ddc:
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department:
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doi: 10.3390/ijms21186737
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title: Deep learning-assisted high-throughput analysis of freeze-fracture replica
images applied to glutamate receptors and calcium channels at hippocampal synapses
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