---
_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:<a href="https://doi.org/10.15479/AT:ISTA:th_997">10.15479/AT:ISTA:th_997</a>
  apa: Chen, C. (2018). <i>Synaptotagmins ensure speed and efficiency of inhibitory
    neurotransmitter release</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT:ISTA:th_997">https://doi.org/10.15479/AT:ISTA:th_997</a>
  chicago: Chen, Chong. “Synaptotagmins Ensure Speed and Efficiency of Inhibitory
    Neurotransmitter Release.” Institute of Science and Technology Austria, 2018.
    <a href="https://doi.org/10.15479/AT:ISTA:th_997">https://doi.org/10.15479/AT:ISTA:th_997</a>.
  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. <i>Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter
    Release</i>. Institute of Science and Technology Austria, 2018, doi:<a href="https://doi.org/10.15479/AT:ISTA:th_997">10.15479/AT:ISTA:th_997</a>.
  short: C. Chen, Synaptotagmins Ensure Speed and Efficiency of Inhibitory Neurotransmitter
    Release, Institute of Science and Technology Austria, 2018.
corr_author: '1'
date_created: 2018-12-11T11:45:49Z
date_published: 2018-03-01T00:00:00Z
date_updated: 2025-07-10T11:54:42Z
day: '01'
ddc:
- '571'
degree_awarded: PhD
department:
- _id: PeJo
doi: 10.15479/AT:ISTA:th_997
file:
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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'
...