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The calcium sensor synaptotagmin 7 is required for synaptic facilitation

It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner(1). At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action...

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Autores principales: Jackman, Skyler L., Turecek, Josef, Belinsky, Justine E., Regehr, Wade G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729191/
https://www.ncbi.nlm.nih.gov/pubmed/26738595
http://dx.doi.org/10.1038/nature16507
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author Jackman, Skyler L.
Turecek, Josef
Belinsky, Justine E.
Regehr, Wade G.
author_facet Jackman, Skyler L.
Turecek, Josef
Belinsky, Justine E.
Regehr, Wade G.
author_sort Jackman, Skyler L.
collection PubMed
description It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner(1). At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release(2). Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses(3), but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release(2,4) and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed(5,6). Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation.
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spelling pubmed-47291912016-07-07 The calcium sensor synaptotagmin 7 is required for synaptic facilitation Jackman, Skyler L. Turecek, Josef Belinsky, Justine E. Regehr, Wade G. Nature Article It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner(1). At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release(2). Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses(3), but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release(2,4) and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed(5,6). Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. 2016-01-07 /pmc/articles/PMC4729191/ /pubmed/26738595 http://dx.doi.org/10.1038/nature16507 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Jackman, Skyler L.
Turecek, Josef
Belinsky, Justine E.
Regehr, Wade G.
The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title_full The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title_fullStr The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title_full_unstemmed The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title_short The calcium sensor synaptotagmin 7 is required for synaptic facilitation
title_sort calcium sensor synaptotagmin 7 is required for synaptic facilitation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729191/
https://www.ncbi.nlm.nih.gov/pubmed/26738595
http://dx.doi.org/10.1038/nature16507
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