Dopamine and gamma band synchrony in schizophrenia--insights from computational and empirical studies.
Kömek K1, Bard Ermentrout G, Walker CP, Cho RY.
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Abstract
Dopamine modulates cortical circuit activity in part through its actions on GABAergic interneurons, including increasing the excitability of fast-spiking interneurons. Though such effects have been demonstrated in single cells, there are no studies that examine how such mechanisms may lead to the effects of dopamine at a neural network level. With this motivation, we investigated the effects of dopamine on synchronization in a simulated neural network composed of excitatory and fast-spiking inhibitory Wang-Buzsaki neurons. The effects of dopamine were implemented through varying leak K+ conductance of the fast-spiking interneurons and the network synchronization within the gamma band (∼40 Hz) was analyzed. Parametrically varying the leak K+ conductance revealed an inverted-U shaped relationship, with low gamma band power at both low and high conductance levels and optimal synchronization at intermediate conductance levels. We also examined the effects of modulating excitability of the inhibitory neurons more generically using an idealized model with theta neurons, with similar findings. Moreover, such a relationship holds when the external input is both tonic and periodic. Our computational results mirror our empirical study of dopamine modulation in schizophrenia and healthy controls, which showed that amphetamine administration increased gamma power in patients but decreased it in controls. Together, our computational and empirical investigations indicate that dopamine can modulate cortical gamma band synchrony in an inverted-U fashion and that the physiologic effects of dopamine on single fast-spiking interneurons can give rise to such non-monotonic effects at the network level.
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
PMID: 22805060 [PubMed - indexed for MEDLINE] PMCID: PMC3697121 Free PMC Article
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Dopamine and gamma band synchrony in schizophrenia--insights from computational and empirical studies.Kömek K1, Bard Ermentrout G, Walker CP, Cho RY.Author informationAbstractDopamine modulates cortical circuit activity in part through its actions on GABAergic interneurons, including increasing the excitability of fast-spiking interneurons. Though such effects have been demonstrated in single cells, there are no studies that examine how such mechanisms may lead to the effects of dopamine at a neural network level. With this motivation, we investigated the effects of dopamine on synchronization in a simulated neural network composed of excitatory and fast-spiking inhibitory Wang-Buzsaki neurons. The effects of dopamine were implemented through varying leak K+ conductance of the fast-spiking interneurons and the network synchronization within the gamma band (∼40 Hz) was analyzed. Parametrically varying the leak K+ conductance revealed an inverted-U shaped relationship, with low gamma band power at both low and high conductance levels and optimal synchronization at intermediate conductance levels. We also examined the effects of modulating excitability of the inhibitory neurons more generically using an idealized model with theta neurons, with similar findings. Moreover, such a relationship holds when the external input is both tonic and periodic. Our computational results mirror our empirical study of dopamine modulation in schizophrenia and healthy controls, which showed that amphetamine administration increased gamma power in patients but decreased it in controls. Together, our computational and empirical investigations indicate that dopamine can modulate cortical gamma band synchrony in an inverted-U fashion and that the physiologic effects of dopamine on single fast-spiking interneurons can give rise to such non-monotonic effects at the network level.© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.PMID: 22805060 [PubMed - indexed for MEDLINE] PMCID: PMC3697121 Free PMC ArticleImages from this publication.See all images (7)Free textPublication Types, MeSH Terms, Substances, Grant SupportLinkOut - more resourcesPubMed Commons homePubMed Commons 0 comments
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