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Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlati...

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Autores principales: Brandalise, Federico, Carta, Stefano, Helmchen, Fritjof, Lisman, John, Gerber, Urs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116082/
https://www.ncbi.nlm.nih.gov/pubmed/27848967
http://dx.doi.org/10.1038/ncomms13480
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author Brandalise, Federico
Carta, Stefano
Helmchen, Fritjof
Lisman, John
Gerber, Urs
author_facet Brandalise, Federico
Carta, Stefano
Helmchen, Fritjof
Lisman, John
Gerber, Urs
author_sort Brandalise, Federico
collection PubMed
description The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells.
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spelling pubmed-51160822017-01-13 Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells Brandalise, Federico Carta, Stefano Helmchen, Fritjof Lisman, John Gerber, Urs Nat Commun Article The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells. Nature Publishing Group 2016-11-16 /pmc/articles/PMC5116082/ /pubmed/27848967 http://dx.doi.org/10.1038/ncomms13480 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Brandalise, Federico
Carta, Stefano
Helmchen, Fritjof
Lisman, John
Gerber, Urs
Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title_full Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title_fullStr Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title_full_unstemmed Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title_short Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells
title_sort dendritic nmda spikes are necessary for timing-dependent associative ltp in ca3 pyramidal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116082/
https://www.ncbi.nlm.nih.gov/pubmed/27848967
http://dx.doi.org/10.1038/ncomms13480
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