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 bur...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-07-01
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| Series: | Frontiers in Computational Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncom.2015.00095/full |
| _version_ | 1818617193459351552 |
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| author | Andrew eOster Boris eGutkin Boris eGutkin Philippe eFaure Philippe eFaure |
| author_facet | Andrew eOster Boris eGutkin Boris eGutkin Philippe eFaure Philippe eFaure |
| author_sort | Andrew eOster |
| collection | DOAJ |
| 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 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. |
| first_indexed | 2024-12-16T17:01:48Z |
| format | Article |
| id | doaj.art-1fe9e72024224ae397f67c2f0b8de7c5 |
| institution | Directory Open Access Journal |
| issn | 1662-5188 |
| language | English |
| last_indexed | 2024-12-16T17:01:48Z |
| publishDate | 2015-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Computational Neuroscience |
| spelling | doaj.art-1fe9e72024224ae397f67c2f0b8de7c52022-12-21T22:23:43ZengFrontiers Media S.A.Frontiers in Computational Neuroscience1662-51882015-07-01910.3389/fncom.2015.00095146968Mechanisms for multiple activity modes of VTA dopamine neuronsAndrew eOster0Boris eGutkin1Boris eGutkin2Philippe eFaure3Philippe eFaure4Eastern Washington UniversityEcole Normale SuperieureNational Research University Higher School of EconomicsNeuroscience Paris Seine (NPS), Universite Pierre et Marie Curie (UM CR18)Centre National de la Recherche Scientifique - UMR8246Midbrain 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 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.http://journal.frontiersin.org/Journal/10.3389/fncom.2015.00095/fullDopamineGABANMDAmodelingVTAbursting |
| spellingShingle | Andrew eOster Boris eGutkin Boris eGutkin Philippe eFaure Philippe eFaure Mechanisms for multiple activity modes of VTA dopamine neurons Frontiers in Computational Neuroscience Dopamine GABA NMDA modeling VTA bursting |
| 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 | Dopamine GABA NMDA modeling VTA bursting |
| url | http://journal.frontiersin.org/Journal/10.3389/fncom.2015.00095/full |
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