---
_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: '1117'
abstract:
- lang: eng
text: 'GABAergic synapses in brain circuits generate inhibitory output signals with
submillisecond latency and temporal precision. Whether the molecular identity
of the release sensor contributes to these signaling properties remains unclear.
Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC)
to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC
terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin
1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced
action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor
at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2
triggered release with shorter latency and higher temporal precision and mediated
faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely
reduced and delayed disynaptic inhibition following parallel fiber stimulation.
Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast
and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author'
acknowledged_ssus:
- _id: Bio
- _id: PreCl
article_processing_charge: No
author:
- 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: Rachel
full_name: Satterield, Rachel
last_name: Satterield
- first_name: Samuel
full_name: Young, Samuel
last_name: Young
- 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 C, Arai itaru, Satterield R, Young S, Jonas PM. Synaptotagmin 2 is the
fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 2017;18(3):723-736.
doi:10.1016/j.celrep.2016.12.067
apa: Chen, C., Arai, itaru, Satterield, R., Young, S., & Jonas, P. M. (2017).
Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell
Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.12.067
chicago: Chen, Chong, itaru Arai, Rachel Satterield, Samuel Young, and Peter M Jonas.
“Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.” Cell
Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2016.12.067.
ieee: C. Chen, itaru Arai, R. Satterield, S. Young, and P. M. Jonas, “Synaptotagmin
2 is the fast Ca2+ sensor at a central inhibitory synapse,” Cell Reports,
vol. 18, no. 3. Cell Press, pp. 723–736, 2017.
ista: Chen C, Arai itaru, Satterield R, Young S, Jonas PM. 2017. Synaptotagmin
2 is the fast Ca2+ sensor at a central inhibitory synapse. Cell Reports. 18(3),
723–736.
mla: Chen, Chong, et al. “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory
Synapse.” Cell Reports, vol. 18, no. 3, Cell Press, 2017, pp. 723–36, doi:10.1016/j.celrep.2016.12.067.
short: C. Chen, itaru Arai, R. Satterield, S. Young, P.M. Jonas, Cell Reports 18
(2017) 723–736.
date_created: 2018-12-11T11:50:14Z
date_published: 2017-01-17T00:00:00Z
date_updated: 2023-09-20T11:32:15Z
day: '17'
ddc:
- '571'
department:
- _id: PeJo
doi: 10.1016/j.celrep.2016.12.067
ec_funded: 1
external_id:
isi:
- '000396470600013'
file:
- access_level: open_access
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:09Z
date_updated: 2018-12-12T10:16:09Z
file_id: '5195'
file_name: IST-2017-751-v1+1_1-s2.0-S2211124716317740-main.pdf
file_size: 4427591
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file_date_updated: 2018-12-12T10:16:09Z
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
issue: '3'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 723 - 736
project:
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P24909-B24
name: Mechanisms of transmitter release at GABAergic synapses
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '268548'
name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
publication: Cell Reports
publication_identifier:
issn:
- '22111247'
publication_status: published
publisher: Cell Press
publist_id: '6245'
pubrep_id: '751'
quality_controlled: '1'
related_material:
record:
- id: '324'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory 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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 18
year: '2017'
...
---
_id: '2031'
abstract:
- lang: eng
text: A puzzling property of synaptic transmission, originally established at the
neuromuscular junction, is that the time course of transmitter release is independent
of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release
is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory
basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o.
Modeling of Ca2+-dependent transmitter release suggests that the invariant time
course of release critically depends on tight coupling between Ca2+ channels and
release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor
coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance
of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation
for the apparent [Ca2+]o independence of the time course of release.
author:
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- 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: Arai itaru, Jonas PM. Nanodomain coupling explains Ca^2+ independence of transmitter
release time course at a fast central synapse. eLife. 2014;3. doi:10.7554/eLife.04057
apa: Arai, itaru, & Jonas, P. M. (2014). Nanodomain coupling explains Ca^2+
independence of transmitter release time course at a fast central synapse. ELife.
eLife Sciences Publications. https://doi.org/10.7554/eLife.04057
chicago: Arai, itaru, and Peter M Jonas. “Nanodomain Coupling Explains Ca^2+ Independence
of Transmitter Release Time Course at a Fast Central Synapse.” ELife. eLife
Sciences Publications, 2014. https://doi.org/10.7554/eLife.04057.
ieee: itaru Arai and P. M. Jonas, “Nanodomain coupling explains Ca^2+ independence
of transmitter release time course at a fast central synapse,” eLife, vol.
3. eLife Sciences Publications, 2014.
ista: Arai itaru, Jonas PM. 2014. Nanodomain coupling explains Ca^2+ independence
of transmitter release time course at a fast central synapse. eLife. 3.
mla: Arai, itaru, and Peter M. Jonas. “Nanodomain Coupling Explains Ca^2+ Independence
of Transmitter Release Time Course at a Fast Central Synapse.” ELife, vol.
3, eLife Sciences Publications, 2014, doi:10.7554/eLife.04057.
short: itaru Arai, P.M. Jonas, ELife 3 (2014).
date_created: 2018-12-11T11:55:19Z
date_published: 2014-12-09T00:00:00Z
date_updated: 2021-01-12T06:54:51Z
day: '09'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.7554/eLife.04057
ec_funded: 1
file:
- access_level: open_access
checksum: c240f915450d4ebe8f95043a2a8c7b1a
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:41Z
date_updated: 2020-07-14T12:45:26Z
file_id: '5094'
file_name: IST-2016-421-v1+1_e04057.full.pdf
file_size: 2239563
relation: main_file
file_date_updated: 2020-07-14T12:45:26Z
has_accepted_license: '1'
intvolume: ' 3'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
project:
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P24909-B24
name: Mechanisms of transmitter release at GABAergic synapses
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '268548'
name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
publist_id: '5041'
pubrep_id: '421'
quality_controlled: '1'
scopus_import: 1
status: public
title: Nanodomain coupling explains Ca^2+ independence of transmitter release time
course at a fast central synapse
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 3
year: '2014'
...