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Author Ermentrout, G. B. ♦ Kirli, Kubra Ekomek ♦ Cho, Raymond Youngjin
Source Directory of Open Access Journals (DOAJ)
Content type Text
Publisher Frontiers Media S.A.
File Format HTM / HTML
Date Created 2014-10-27
Copyright Year ©2014
Language English
Subject Domain (in LCC) RC321-571
Subject Keyword Neuropsychiatry ♦ Biological psychiatry ♦ Neurosciences ♦ Gamma band ♦ NMDA receptor ♦ Internal medicine ♦ Cortical oscillations ♦ Medicine ♦ Schizophrenia ♦ Computational modeling ♦ Synchrony
Abstract N-methyl-D-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia. The illness is also characterized by gamma oscillatory disturbances, which can be evaluated with precise frequency specificity employing auditory cortical entrainment paradigms. This computational study investigates how synaptic NMDA hypofunction may give rise to network level oscillatory deficits as indexed by entrainment paradigms. We developed a computational model of a local cortical circuit with pyramidal cells and fast-spiking interneurons (FSI), incorporating NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA), and γ-aminobutyric acid (GABA) synaptic kinetics. We evaluated the effects of varying NMDA conductance on FSIs and pyramidal cells, as well as AMPA to NMDA ratio. We also examined the differential effects across a broad range of entrainment frequencies as a function of NMDA conductance. Varying NMDA conductance onto FSIs revealed an inverted-U relation with network gamma whereas NMDA conductance onto the pyramidal cells had a more monotonic relationship. Varying NMDA vs. AMPA conductance onto FSIs demonstrated the necessity of AMPA in the generation of gamma while NMDA receptors had a modulatory role. Finally, reducing NMDA conductance onto FSI and varying the stimulus input frequency reproduced the specific reductions in gamma range (~40 Hz) as observed in schizophrenia studies. Our computational study showed that reductions in NMDA conductance onto FSIs can reproduce similar disturbances in entrainment to periodic stimuli within the gamma range as reported in schizophrenia studies. These findings provide a mechanistic account of how specific cellular level disturbances can give rise to circuitry level pathophysiologic disturbance in schizophrenia.
ISSN 16625188
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study
Learning Resource Type Article
Publisher Date 2014-10-01
e-ISSN 16625188
Journal Frontiers in Computational Neuroscience
Volume Number 8


Source: Directory of Open Access Journals (DOAJ)