---
_id: '324'
abstract:
- lang: eng
text: Neuronal networks in the brain consist of two main types of neuron, glutamatergic
principal neurons and GABAergic interneurons. Although these interneurons only
represent 10–20% of the whole population, they mediate feedback and feedforward
inhibition and are involved in the generation of high-frequency network oscillations.
A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing
(PV+) subtypes, is the speed of signaling at their output synapse across species
and brain regions. Several molecular and subcellular factors may underlie the
submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q
type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors
of exocytosis. However, whether the molecular identity of the release sensor contributes
to these signaling properties remains unclear. Besides, these interneurons are
mainly show depression in response to train of stimuli. How could they keep sufficient
release to control the activity of postsynaptic principal neurons during high
network activity, is largely elusive. For my Ph.D. work, we firstly examined the
Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC)
synapse in the 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% compared to the wild-type control, identifying Syt2 as the major
Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed
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 the release sensor at BC–PC synapse
ensures fast feedforward inhibition in cerebellar microcircuits. Additionally,
we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic
transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates
asynchronous transmitter release and facilitation at synapses. However, it is
strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output
synapses of these neurons produce only minimal asynchronous release and show depression
rather than facilitation. How could Syt7, a facilitation sensor, contribute to
the depressed inhibitory synaptic transmission needs to be further investigated
and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes
to asynchronous release, pool replenishment and facilitation. In combination,
these three effects ensure efficient transmitter release during high‑frequency
activity and guarantee frequency independence of inhibition. Taken together, our
results confirmed that Syt2, which has the fastest kinetic properties among all
synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic
transmission, contributing to the speed and temporal precision of transmitter
release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin
member in the output synapses of cerebellar BCs, is used for ensuring efficient
inhibitor synaptic transmission during high activity.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
citation:
ama: Chen C. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter
release. 2018. doi:10.15479/AT:ISTA:th_997
apa: Chen, C. (2018). Synaptotagmins ensure speed and efficiency of inhibitory
neurotransmitter release. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_997
chicago: Chen, Chong. “Synaptotagmins Ensure Speed and Efficiency of Inhibitory
Neurotransmitter Release.” Institute of Science and Technology Austria, 2018.
https://doi.org/10.15479/AT:ISTA:th_997.
ieee: C. Chen, “Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter
release,” Institute of Science and Technology Austria, 2018.
ista: Chen C. 2018. Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter
release. Institute of Science and Technology Austria.
mla: Chen, Chong. Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter
Release. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_997.
short: C. Chen, Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter
Release, Institute of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:45:49Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2023-09-27T12:26:03Z
day: '01'
ddc:
- '571'
degree_awarded: PhD
department:
- _id: PeJo
doi: 10.15479/AT:ISTA:th_997
file:
- access_level: open_access
checksum: 8e163ae9e927401b9fa7c1b3e6a3631a
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:58Z
date_updated: 2020-07-14T12:46:04Z
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checksum: f7d7260029a5fbb5c982db61328ade52
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file_name: 2018_Thesis_chong_source.pages
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relation: source_file
file_date_updated: 2020-07-14T12:46:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '110'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '7541'
pubrep_id: '997'
related_material:
record:
- id: '1117'
relation: part_of_dissertation
status: public
- id: '749'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
title: Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...