---
_id: '14843'
abstract:
- lang: eng
text: The coupling between Ca2+ channels and release sensors is a key factor defining
the signaling properties of a synapse. However, the coupling nanotopography at
many synapses remains unknown, and it is unclear how it changes during development.
To address these questions, we examined coupling at the cerebellar inhibitory
basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
by paired recording and intracellular pipette perfusion revealed that the effects
of exogenous Ca2+ chelators decreased during development, despite constant reliance
of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
vesicles were only clustered at later developmental stages. Modeling suggested
a developmental transformation from a more random to a more clustered coupling
nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
for advice on numerical solution of partial differential equations, Maria Reva for
help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
and Machine Shop). The project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: No
article_type: original
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse. Neuron. doi:10.1016/j.neuron.2023.12.002
apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., &
Jonas, P. M. (n.d.). Developmental transformation of Ca2+ channel-vesicle nanotopography
at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002
chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, n.d.
https://doi.org/10.1016/j.neuron.2023.12.002.
ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse,” Neuron. Elsevier.
ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. Developmental
transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse.
Neuron.
mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron, Elsevier, doi:10.1016/j.neuron.2023.12.002.
short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
Neuron (n.d.).
date_created: 2024-01-21T23:00:56Z
date_published: 2024-01-11T00:00:00Z
date_updated: 2024-03-05T09:31:24Z
day: '11'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
pmid:
- '38215739'
language:
- iso: eng
month: '01'
oa_version: None
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: inpress
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '12875'
abstract:
- lang: eng
text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory
integration and is composed of a rich diversity of excitatory and inhibitory neurons
and glia. However, the developmental principles directing the generation of SC
cell-type diversity are not understood. Here, we pursued systematic cell lineage
tracing in silico and in vivo, preserving full spatial information, using genetic
mosaic analysis with double markers (MADM)-based clonal analysis with single-cell
sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed
that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual
resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron
types, even at the stage of terminal division. While individual clonal units show
no pre-defined cellular composition, the establishment of appropriate relative
proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively,
our findings provide an inaugural framework at the single-RGP/-cell level of the
mammalian SC ontogeny.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Liqun Luo for his continued support, for providing essential
resources for generating Fzd10-CreER mice which were generated in his laboratory,
and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic
mouse line for this study; A. Heger for mouse colony management; R. Beattie and
T. Asenov for designing and producing components of acute slice recovery chamber
for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial
experiments, technical support and/or assistance. This study was supported by the
Scientific Service Units (SSU) of IST Austria through resources provided by the
Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine
Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission
(IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds;
the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation)
to S.H. "
article_processing_charge: Yes (via OA deal)
article_type: comment
author:
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Thomas
full_name: Krausgruber, Thomas
last_name: Krausgruber
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Martin
full_name: Schrammel, Martin
id: f13e7cae-e8bd-11ed-841a-96dedf69f46d
last_name: Schrammel
- first_name: Natalie Y
full_name: Özgen, Natalie Y
id: e68ece33-f6e0-11ea-865d-ae1031dcc090
last_name: Özgen
- first_name: Alexis
full_name: Ivec, Alexis
id: 1d144691-e8be-11ed-9b33-bdd3077fad4c
last_name: Ivec
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
date_created: 2023-04-27T09:41:48Z
date_published: 2024-01-17T00:00:00Z
date_updated: 2025-05-14T09:39:37Z
day: '17'
ddc:
- '570'
department:
- _id: SiHi
- _id: RySh
doi: 10.1016/j.neuron.2023.11.009
external_id:
pmid:
- '38096816'
file:
- access_level: open_access
checksum: 32b3788f7085cf44a84108d8faaff3ce
content_type: application/pdf
creator: dernst
date_created: 2024-02-06T13:56:15Z
date_updated: 2024-02-06T13:56:15Z
file_id: '14944'
file_name: 2024_Neuron_Cheung.pdf
file_size: 5942467
relation: main_file
success: 1
file_date_updated: 2024-02-06T13:56:15Z
has_accepted_license: '1'
intvolume: ' 112'
issue: '2'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
oa: 1
oa_version: Published Version
page: 230-246.e11
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F07805
name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: Neuron
publication_identifier:
eisbn:
- '1234995621'
issn:
- 0896-6273
issnl:
- 1234-5678
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/
scopus_import: '1'
status: public
title: Multipotent progenitors instruct ontogeny of the superior colliculus
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
_id: '13173'
abstract:
- lang: eng
text: GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
terminals in the brain, except in medial habenula (MHb) terminals, which show
robust potentiation. However, mechanisms underlying this enigmatic potentiation
remain elusive. Here, we report that GBR activation on MHb terminals induces an
activity-dependent transition from a facilitating, tonic to a depressing, phasic
neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic
release exhibit distinct coupling distances and are selectively affected by deletion
of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2),
respectively. SPO modulates augmentation, the short-term plasticity associated
with tonic release, and CAPS2 retains the increased RRP for initial responses
in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization
of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed
a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane
protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the
release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent
recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes.
Overall, these results indicate that GBR activation translocates CAPS2 to the
AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent
RRP increase. Thus, we discovered structural and molecular mechanisms underlying
tonic and phasic neurotransmitter release and their transition by GBR activation
in MHb terminals.
article_processing_charge: No
author:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic
GABAB receptor activation in medial habenula terminals. 2023. doi:10.15479/AT:ISTA:13173
apa: Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release
by presynaptic GABAB receptor activation in medial habenula terminals. Institute
of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13173
chicago: Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release
by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute
of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13173.
ieee: R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by
presynaptic GABAB receptor activation in medial habenula terminals.” Institute
of Science and Technology Austria, 2023.
ista: Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release
by presynaptic GABAB receptor activation in medial habenula terminals, Institute
of Science and Technology Austria, 10.15479/AT:ISTA:13173.
mla: Shigemoto, Ryuichi. Transition from Tonic to Phasic Neurotransmitter Release
by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals. Institute
of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13173.
short: R. Shigemoto, (2023).
date_created: 2023-06-29T13:16:42Z
date_published: 2023-07-29T00:00:00Z
date_updated: 2024-02-21T12:19:26Z
day: '29'
ddc:
- '571'
department:
- _id: RySh
doi: 10.15479/AT:ISTA:13173
file:
- access_level: closed
checksum: ed59170869ba621f89f7c1894092192f
content_type: application/x-zip-compressed
creator: shigemot
date_created: 2023-06-29T13:11:22Z
date_updated: 2023-11-17T14:30:44Z
description: After review an updated version of the data is provided
file_id: '13174'
file_name: Raw data for Koppensteiner et al.zip
file_size: 542873672
relation: main_file
title: Outdated Version
- access_level: open_access
checksum: c07860eb82b4d367245f1b589fe5c250
content_type: application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
creator: patrickd
date_created: 2023-11-17T14:13:02Z
date_updated: 2023-11-17T14:13:02Z
file_id: '14550'
file_name: 11-17-23 Updated Koppensteiner et al. raw data.xlsx
file_size: 915079
relation: main_file
success: 1
- access_level: open_access
checksum: abf84b1699edac4349dc3a92d466fb7b
content_type: application/x-zip-compressed
creator: dernst
date_created: 2024-02-06T07:21:43Z
date_updated: 2024-02-06T07:21:43Z
file_id: '14942'
file_name: EM_Images.zip
file_size: 544868924
relation: main_file
success: 1
file_date_updated: 2024-02-06T07:21:43Z
has_accepted_license: '1'
keyword:
- medial habenula
- GABAB receptor
- vesicle release
- Flash and Freeze
- Flash and Freeze-fracture
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '07'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
status: public
title: Transition from tonic to phasic neurotransmitter release by presynaptic GABAB
receptor activation in medial habenula terminals
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '13202'
abstract:
- lang: eng
text: Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an essential role
in neuronal activities through interaction with various proteins involved in signaling
at membranes. However, the distribution pattern of PI(4,5)P2 and the association
with these proteins on the neuronal cell membranes remain elusive. In this study,
we established a method for visualizing PI(4,5)P2 by SDS-digested freeze-fracture
replica labeling (SDS-FRL) to investigate the quantitative nanoscale distribution
of PI(4,5)P2 in cryo-fixed brain. We demonstrate that PI(4,5)P2 forms tiny clusters
with a mean size of ∼1000 nm2 rather than randomly distributed in cerebellar neuronal
membranes in male C57BL/6J mice. These clusters show preferential accumulation
in specific membrane compartments of different cell types, in particular, in Purkinje
cell (PC) spines and granule cell (GC) presynaptic active zones. Furthermore,
we revealed extensive association of PI(4,5)P2 with CaV2.1 and GIRK3 across different
membrane compartments, whereas its association with mGluR1α was compartment specific.
These results suggest that our SDS-FRL method provides valuable insights into
the physiological functions of PI(4,5)P2 in neurons.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: This work was supported by The Institute of Science and Technology
(IST) Austria, the European Union's Horizon 2020 Research and Innovation Program
under the Marie Skłodowska-Curie Grant Agreement No. 793482 (to K.E.) and by the
European Research Council (ERC) Grant Agreement No. 694539 (to R.S.). We thank Nicoleta
Condruz (IST Austria, Klosterneuburg, Austria) for technical assistance with sample
preparation, the Electron Microscopy Facility of IST Austria (Klosterneuburg, Austria)
for technical support with EM works, Natalia Baranova (University of Vienna, Vienna,
Austria) and Martin Loose (IST Austria, Klosterneuburg, Austria) for advice on liposome
preparation, and Yugo Fukazawa (University of Fukui, Fukui, Japan) for comments.
article_processing_charge: No
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: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- 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, Le Monnier E, Shigemoto R. Nanoscale phosphoinositide distribution
on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience.
2023;43(23):4197-4216. doi:10.1523/JNEUROSCI.1514-22.2023
apa: Eguchi, K., Le Monnier, E., & Shigemoto, R. (2023). Nanoscale phosphoinositide
distribution on cell membranes of mouse cerebellar neurons. The Journal of
Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1514-22.2023
chicago: Eguchi, Kohgaku, Elodie Le Monnier, and Ryuichi Shigemoto. “Nanoscale Phosphoinositide
Distribution on Cell Membranes of Mouse Cerebellar Neurons.” The Journal of
Neuroscience. Society for Neuroscience, 2023. https://doi.org/10.1523/JNEUROSCI.1514-22.2023.
ieee: K. Eguchi, E. Le Monnier, and R. Shigemoto, “Nanoscale phosphoinositide distribution
on cell membranes of mouse cerebellar neurons,” The Journal of Neuroscience,
vol. 43, no. 23. Society for Neuroscience, pp. 4197–4216, 2023.
ista: Eguchi K, Le Monnier E, Shigemoto R. 2023. Nanoscale phosphoinositide distribution
on cell membranes of mouse cerebellar neurons. The Journal of Neuroscience. 43(23),
4197–4216.
mla: Eguchi, Kohgaku, et al. “Nanoscale Phosphoinositide Distribution on Cell Membranes
of Mouse Cerebellar Neurons.” The Journal of Neuroscience, vol. 43, no.
23, Society for Neuroscience, 2023, pp. 4197–216, doi:10.1523/JNEUROSCI.1514-22.2023.
short: K. Eguchi, E. Le Monnier, R. Shigemoto, The Journal of Neuroscience 43 (2023)
4197–4216.
date_created: 2023-07-09T22:01:12Z
date_published: 2023-06-07T00:00:00Z
date_updated: 2023-10-18T07:12:47Z
day: '07'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.1514-22.2023
ec_funded: 1
external_id:
isi:
- '001020132100005'
pmid:
- '37160366'
file:
- access_level: open_access
checksum: 70b2141870e0bf1c94fd343e18fdbc32
content_type: application/pdf
creator: alisjak
date_created: 2023-07-10T09:04:58Z
date_updated: 2023-07-10T09:04:58Z
file_id: '13205'
file_name: 2023_JN_Eguchi.pdf
file_size: 7794425
relation: main_file
success: 1
file_date_updated: 2023-07-10T09:04:58Z
has_accepted_license: '1'
intvolume: ' 43'
isi: 1
issue: '23'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 4197-4216
pmid: 1
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'
publication: The 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: Nanoscale phosphoinositide distribution on cell membranes of mouse cerebellar
neurons
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 43
year: '2023'
...
---
_id: '14253'
abstract:
- lang: eng
text: Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM)
are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration
of intracellular signaling machinery near ER-PM junctions allows these domains
to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular
compartmentalization of protein kinase A (PKA) signaling also regulates essential
cellular functions, however, no specific association between PKA and ER-PM junctional
domains is known. Here, we show that in brain neurons type I PKA is directed to
Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific
anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and
ER-resident VAP proteins results in the concentration of type I PKA between stacked
ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome
enables reciprocal regulation between PKA and Ca2+ signaling machinery to support
Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal
ER-PM junctions support a receptor-independent form of PKA signaling driven by
membrane depolarization and intracellular Ca2+, allowing conversion of information
encoded in electrical signals into biochemical changes universally recognized
throughout the cell.
acknowledgement: We thank Kayla Templeton and Peter Turcanu for technical assistance,
Michelle Salemi for assistance with LC-MS data acquisition and analysis, Dr. Belvin
Gong for advice on monoclonal antibody generation, Drs. Maria Casas Prat and Eamonn
Dickson for assistance with super-resolution TIRF microscopy, Dr. Oscar Cerda for
assistance with the design of TAT-FFAT peptides, Dr. Fernando Santana for helpful
discussions, and Dr. Jodi Nunnari for a careful reading of our manuscript. We also
thank Dr. Alan Howe, Dr. Sohum Mehta, and Dr. Jin Zhang for providing plasmids used
in this study. This project was funded by NIH Grants R01NS114210 and R21NS101648
(J.S.T.), and F32NS108519 (N.C.V.).
article_number: '5231'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicholas C.
full_name: Vierra, Nicholas C.
last_name: Vierra
- first_name: Luisa
full_name: Ribeiro-Silva, Luisa
last_name: Ribeiro-Silva
- first_name: Michael
full_name: Kirmiz, Michael
last_name: Kirmiz
- first_name: Deborah
full_name: Van Der List, Deborah
last_name: Van Der List
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Olivia A.
full_name: Mack, Olivia A.
last_name: Mack
- first_name: James
full_name: Carroll, James
last_name: Carroll
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Sue A.
full_name: Aicher, Sue A.
last_name: Aicher
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: James S.
full_name: Trimmer, James S.
last_name: Trimmer
citation:
ama: Vierra NC, Ribeiro-Silva L, Kirmiz M, et al. Neuronal ER-plasma membrane junctions
couple excitation to Ca2+-activated PKA signaling. Nature Communications.
2023;14. doi:10.1038/s41467-023-40930-6
apa: Vierra, N. C., Ribeiro-Silva, L., Kirmiz, M., Van Der List, D., Bhandari, P.,
Mack, O. A., … Trimmer, J. S. (2023). Neuronal ER-plasma membrane junctions couple
excitation to Ca2+-activated PKA signaling. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-023-40930-6
chicago: Vierra, Nicholas C., Luisa Ribeiro-Silva, Michael Kirmiz, Deborah Van Der
List, Pradeep Bhandari, Olivia A. Mack, James Carroll, et al. “Neuronal ER-Plasma
Membrane Junctions Couple Excitation to Ca2+-Activated PKA Signaling.” Nature
Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-40930-6.
ieee: N. C. Vierra et al., “Neuronal ER-plasma membrane junctions couple
excitation to Ca2+-activated PKA signaling,” Nature Communications, vol.
14. Springer Nature, 2023.
ista: Vierra NC, Ribeiro-Silva L, Kirmiz M, Van Der List D, Bhandari P, Mack OA,
Carroll J, Le Monnier E, Aicher SA, Shigemoto R, Trimmer JS. 2023. Neuronal ER-plasma
membrane junctions couple excitation to Ca2+-activated PKA signaling. Nature Communications.
14, 5231.
mla: Vierra, Nicholas C., et al. “Neuronal ER-Plasma Membrane Junctions Couple Excitation
to Ca2+-Activated PKA Signaling.” Nature Communications, vol. 14, 5231,
Springer Nature, 2023, doi:10.1038/s41467-023-40930-6.
short: N.C. Vierra, L. Ribeiro-Silva, M. Kirmiz, D. Van Der List, P. Bhandari, O.A.
Mack, J. Carroll, E. Le Monnier, S.A. Aicher, R. Shigemoto, J.S. Trimmer, Nature
Communications 14 (2023).
date_created: 2023-09-03T22:01:14Z
date_published: 2023-08-26T00:00:00Z
date_updated: 2023-09-06T06:53:32Z
day: '26'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1038/s41467-023-40930-6
external_id:
pmid:
- '37633939'
file:
- access_level: open_access
checksum: 6ab8aab4e957f626a09a1c73db3388fb
content_type: application/pdf
creator: dernst
date_created: 2023-09-06T06:50:07Z
date_updated: 2023-09-06T06:50:07Z
file_id: '14270'
file_name: 2023_NatureComm_Vierra.pdf
file_size: 9412549
relation: main_file
success: 1
file_date_updated: 2023-09-06T06:50:07Z
has_accepted_license: '1'
intvolume: ' 14'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA
signaling
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '10889'
abstract:
- lang: eng
text: Genetically encoded tags have introduced extensive lines of application from
purification of tagged proteins to their visualization at the single molecular,
cellular, histological and whole-body levels. Combined with other rapidly developing
technologies such as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated
protein 9 (Cas9) system, proteomics, super-resolution microscopy and proximity
labeling, a large variety of genetically encoded tags have been developed in the
last two decades. In this review, I focus on the current status of tag development
for electron microscopic (EM) visualization of proteins with metal particle labeling.
Compared with conventional immunoelectron microscopy using gold particles, tag-mediated
metal particle labeling has several advantages that could potentially improve
the sensitivity, spatial and temporal resolution, and applicability to a wide
range of proteins of interest (POIs). It may enable researchers to detect single
molecules in situ, allowing the quantitative measurement of absolute numbers and
exact localization patterns of POI in the ultrastructural context. Thus, genetically
encoded tags for EM could revolutionize the field as green fluorescence protein
did for light microscopy, although we still have many challenges to overcome before
reaching this goal.
acknowledgement: European Research Council Advanced Grant (694539 to R.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Shigemoto R. Electron microscopic visualization of single molecules by tag-mediated
metal particle labeling. Microscopy. 2022;71(Supplement_1):i72-i80. doi:10.1093/jmicro/dfab048
apa: Shigemoto, R. (2022). Electron microscopic visualization of single molecules
by tag-mediated metal particle labeling. Microscopy. Oxford Academic. https://doi.org/10.1093/jmicro/dfab048
chicago: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules
by Tag-Mediated Metal Particle Labeling.” Microscopy. Oxford Academic,
2022. https://doi.org/10.1093/jmicro/dfab048.
ieee: R. Shigemoto, “Electron microscopic visualization of single molecules by tag-mediated
metal particle labeling,” Microscopy, vol. 71, no. Supplement_1. Oxford
Academic, pp. i72–i80, 2022.
ista: Shigemoto R. 2022. Electron microscopic visualization of single molecules
by tag-mediated metal particle labeling. Microscopy. 71(Supplement_1), i72–i80.
mla: Shigemoto, Ryuichi. “Electron Microscopic Visualization of Single Molecules
by Tag-Mediated Metal Particle Labeling.” Microscopy, vol. 71, no. Supplement_1,
Oxford Academic, 2022, pp. i72–80, doi:10.1093/jmicro/dfab048.
short: R. Shigemoto, Microscopy 71 (2022) i72–i80.
date_created: 2022-03-20T23:01:39Z
date_published: 2022-03-01T00:00:00Z
date_updated: 2023-08-03T06:08:01Z
day: '01'
department:
- _id: RySh
doi: 10.1093/jmicro/dfab048
ec_funded: 1
external_id:
isi:
- '000768384100011'
pmid:
- '35275179'
intvolume: ' 71'
isi: 1
issue: Supplement_1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/jmicro/dfab048
month: '03'
oa: 1
oa_version: Published Version
page: i72-i80
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: Microscopy
publication_identifier:
eissn:
- 2050-5701
issn:
- 2050-5698
publication_status: published
publisher: Oxford Academic
quality_controlled: '1'
scopus_import: '1'
status: public
title: Electron microscopic visualization of single molecules by tag-mediated metal
particle labeling
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 71
year: '2022'
...
---
_id: '10890'
abstract:
- lang: eng
text: Upon the arrival of action potentials at nerve terminals, neurotransmitters
are released from synaptic vesicles (SVs) by exocytosis. CaV2.1, 2.2, and 2.3
are the major subunits of the voltage-gated calcium channel (VGCC) responsible
for increasing intraterminal calcium levels and triggering SV exocytosis in the
central nervous system (CNS) synapses. The two-dimensional analysis of CaV2 distributions
using sodium dodecyl sulfate (SDS)-digested freeze-fracture replica labeling (SDS-FRL)
has revealed their numbers, densities, and nanoscale clustering patterns in individual
presynaptic active zones. The variation in these properties affects the coupling
of VGCCs with calcium sensors on SVs, synaptic efficacy, and temporal precision
of transmission. In this study, we summarize how the morphological parameters
of CaV2 distribution obtained using SDS-FRL differ depending on the different
types of synapses and could correspond to functional properties in synaptic transmission.
acknowledgement: "This work was supported by the European Research Council advanced
grant No. 694539 and the joint German-Austrian DFG and FWF project SYNABS (FWF:
I-4638-B) to RS.\r\nThe authors thank Walter Kaufmann for his critical comments
on the manuscript."
article_number: '846615'
article_processing_charge: No
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: Jacqueline-Claire
full_name: Montanaro-Punzengruber, Jacqueline-Claire
id: 3786AB44-F248-11E8-B48F-1D18A9856A87
last_name: Montanaro-Punzengruber
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- 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, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. The number
and distinct clustering patterns of voltage-gated Calcium channels in nerve terminals.
Frontiers in Neuroanatomy. 2022;16. doi:10.3389/fnana.2022.846615
apa: Eguchi, K., Montanaro-Punzengruber, J.-C., Le Monnier, E., & Shigemoto,
R. (2022). The number and distinct clustering patterns of voltage-gated Calcium
channels in nerve terminals. Frontiers in Neuroanatomy. Frontiers. https://doi.org/10.3389/fnana.2022.846615
chicago: Eguchi, Kohgaku, Jacqueline-Claire Montanaro-Punzengruber, Elodie Le Monnier,
and Ryuichi Shigemoto. “The Number and Distinct Clustering Patterns of Voltage-Gated
Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy. Frontiers,
2022. https://doi.org/10.3389/fnana.2022.846615.
ieee: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, and R. Shigemoto,
“The number and distinct clustering patterns of voltage-gated Calcium channels
in nerve terminals,” Frontiers in Neuroanatomy, vol. 16. Frontiers, 2022.
ista: Eguchi K, Montanaro-Punzengruber J-C, Le Monnier E, Shigemoto R. 2022. The
number and distinct clustering patterns of voltage-gated Calcium channels in nerve
terminals. Frontiers in Neuroanatomy. 16, 846615.
mla: Eguchi, Kohgaku, et al. “The Number and Distinct Clustering Patterns of Voltage-Gated
Calcium Channels in Nerve Terminals.” Frontiers in Neuroanatomy, vol. 16,
846615, Frontiers, 2022, doi:10.3389/fnana.2022.846615.
short: K. Eguchi, J.-C. Montanaro-Punzengruber, E. Le Monnier, R. Shigemoto, Frontiers
in Neuroanatomy 16 (2022).
date_created: 2022-03-20T23:01:39Z
date_published: 2022-02-24T00:00:00Z
date_updated: 2024-10-29T07:57:26Z
day: '24'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3389/fnana.2022.846615
ec_funded: 1
external_id:
isi:
- '000766662700001'
pmid:
- '35280978'
file:
- access_level: open_access
checksum: 51ec9b90e7da919e22c01a15489eaacd
content_type: application/pdf
creator: dernst
date_created: 2022-03-21T09:41:19Z
date_updated: 2022-03-21T09:41:19Z
file_id: '10911'
file_name: 2022_FrontiersNeuroanatomy_Eguchi.pdf
file_size: 2416395
relation: main_file
success: 1
file_date_updated: 2022-03-21T09:41:19Z
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 05970B30-7A3F-11EA-A408-12923DDC885E
grant_number: I04638
name: LGI1 antibody-induced pathophysiology in synapses
publication: Frontiers in Neuroanatomy
publication_identifier:
eissn:
- '16625129'
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: The number and distinct clustering patterns of voltage-gated Calcium channels
in nerve 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: 16
year: '2022'
...
---
_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: '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: '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: 2024-03-25T23:30:16Z
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: '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: '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: 2024-03-25T23:30:16Z
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: '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: '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: 2024-03-25T23:30:16Z
day: '14'
ddc:
- '570'
department:
- _id: RySh
doi: 10.3390/ijms21186737
ec_funded: 1
external_id:
isi:
- '000579945300001'
file:
- access_level: open_access
checksum: 2e4f62f3cfe945b7391fc3070e5a289f
content_type: application/pdf
creator: dernst
date_created: 2020-09-21T14:08:58Z
date_updated: 2020-09-21T14:08:58Z
file_id: '8551'
file_name: 2020_JournMolecSciences_Kleindienst.pdf
file_size: 5748456
relation: main_file
success: 1
file_date_updated: 2020-09-21T14:08:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '18'
language:
- iso: eng
month: '09'
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: 25D32BC0-B435-11E9-9278-68D0E5697425
name: Mechanism of formation and maintenance of input side-dependent asymmetry in
the hippocampus
- _id: 26436750-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '785907'
name: Human Brain Project Specific Grant Agreement 2 (HBP SGA 2)
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
related_material:
record:
- id: '9562'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Deep learning-assisted high-throughput analysis of freeze-fracture replica
images applied to glutamate receptors and calcium channels at hippocampal 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: 21
year: '2020'
...
---
_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: '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: '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:
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pmid:
- '32252271'
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publication_identifier:
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title: Density of GABAB receptors is reduced in granule cells of the hippocampus in
a mouse model of Alzheimer's disease
tmp:
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legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
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...