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Mechanisms for multiple activity modes of VTA dopamine neurons

Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal burs...

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Autores principales: Oster, Andrew, Faure, Philippe, Gutkin, Boris S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516885/
https://www.ncbi.nlm.nih.gov/pubmed/26283955
http://dx.doi.org/10.3389/fncom.2015.00095
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author Oster, Andrew
Faure, Philippe
Gutkin, Boris S.
author_facet Oster, Andrew
Faure, Philippe
Gutkin, Boris S.
author_sort Oster, Andrew
collection PubMed
description Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta (SNc) DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.
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spelling pubmed-45168852015-08-17 Mechanisms for multiple activity modes of VTA dopamine neurons Oster, Andrew Faure, Philippe Gutkin, Boris S. Front Comput Neurosci Neuroscience Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta (SNc) DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition. Frontiers Media S.A. 2015-07-28 /pmc/articles/PMC4516885/ /pubmed/26283955 http://dx.doi.org/10.3389/fncom.2015.00095 Text en Copyright © 2015 Oster, Faure and Gutkin. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Oster, Andrew
Faure, Philippe
Gutkin, Boris S.
Mechanisms for multiple activity modes of VTA dopamine neurons
title Mechanisms for multiple activity modes of VTA dopamine neurons
title_full Mechanisms for multiple activity modes of VTA dopamine neurons
title_fullStr Mechanisms for multiple activity modes of VTA dopamine neurons
title_full_unstemmed Mechanisms for multiple activity modes of VTA dopamine neurons
title_short Mechanisms for multiple activity modes of VTA dopamine neurons
title_sort mechanisms for multiple activity modes of vta dopamine neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516885/
https://www.ncbi.nlm.nih.gov/pubmed/26283955
http://dx.doi.org/10.3389/fncom.2015.00095
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