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Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release
Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397209/ https://www.ncbi.nlm.nih.gov/pubmed/22811938 http://dx.doi.org/10.1155/2012/203536 |
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author | Amaral, Michelle D. Pozzo-Miller, Lucas |
author_facet | Amaral, Michelle D. Pozzo-Miller, Lucas |
author_sort | Amaral, Michelle D. |
collection | PubMed |
description | Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF application to CA1 pyramidal neurons, the frequency of miniature excitatory postsynaptic currents (mEPSC) increased significantly within 30 seconds; mEPSC amplitude and kinetics were unchanged. This effect was mediated via TrkB receptor activation and required both full intracellular Ca(2+) stores as well as extracellular Ca(2+). Consistent with a role of Ca(2+)-permeable plasma membrane channels of the TRPC family, the inhibitor SKF96365 prevented the BDNF-induced increase in mEPSC frequency. Furthermore, labeling presynaptic terminals with amphipathic styryl dyes and then monitoring their post-BDNF destaining in slice cultures by multiphoton excitation microscopy revealed that the increase in frequency of mEPSCs reflects vesicular fusion events. Indeed, BDNF application to CA3-CA1 synapses in TTX rapidly enhanced FM1-43 or FM2-10 destaining with a time course that paralleled the phase of increased mEPSC frequency. We conclude that BDNF increases mEPSC frequency by boosting vesicular fusion through a presynaptic, Ca(2+)-dependent mechanism involving TrkB receptors, Ca(2+) stores, and TRPC channels. |
format | Online Article Text |
id | pubmed-3397209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33972092012-07-18 Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release Amaral, Michelle D. Pozzo-Miller, Lucas Neural Plast Research Article Brain-derived neurotrophic factor (BDNF) is well known as a survival factor during brain development as well as a regulator of adult synaptic plasticity. One potential mechanism to initiate BDNF actions is through its modulation of quantal presynaptic transmitter release. In response to local BDNF application to CA1 pyramidal neurons, the frequency of miniature excitatory postsynaptic currents (mEPSC) increased significantly within 30 seconds; mEPSC amplitude and kinetics were unchanged. This effect was mediated via TrkB receptor activation and required both full intracellular Ca(2+) stores as well as extracellular Ca(2+). Consistent with a role of Ca(2+)-permeable plasma membrane channels of the TRPC family, the inhibitor SKF96365 prevented the BDNF-induced increase in mEPSC frequency. Furthermore, labeling presynaptic terminals with amphipathic styryl dyes and then monitoring their post-BDNF destaining in slice cultures by multiphoton excitation microscopy revealed that the increase in frequency of mEPSCs reflects vesicular fusion events. Indeed, BDNF application to CA3-CA1 synapses in TTX rapidly enhanced FM1-43 or FM2-10 destaining with a time course that paralleled the phase of increased mEPSC frequency. We conclude that BDNF increases mEPSC frequency by boosting vesicular fusion through a presynaptic, Ca(2+)-dependent mechanism involving TrkB receptors, Ca(2+) stores, and TRPC channels. Hindawi Publishing Corporation 2012 2012-07-03 /pmc/articles/PMC3397209/ /pubmed/22811938 http://dx.doi.org/10.1155/2012/203536 Text en Copyright © 2012 M. D. Amaral and L. Pozzo-Miller. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Amaral, Michelle D. Pozzo-Miller, Lucas Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title | Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title_full | Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title_fullStr | Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title_full_unstemmed | Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title_short | Intracellular Ca(2+) Stores and Ca(2+) Influx Are Both Required for BDNF to Rapidly Increase Quantal Vesicular Transmitter Release |
title_sort | intracellular ca(2+) stores and ca(2+) influx are both required for bdnf to rapidly increase quantal vesicular transmitter release |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397209/ https://www.ncbi.nlm.nih.gov/pubmed/22811938 http://dx.doi.org/10.1155/2012/203536 |
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