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dc.contributor.authorMäki-Marttunen, Tuomo
dc.contributor.authorDevor, Anna
dc.contributor.authorPhillips, William A
dc.contributor.authorDale, Anders M.
dc.contributor.authorAndreassen, Ole Andreas
dc.contributor.authorEinevoll, Gaute
dc.date.accessioned2020-01-14T16:36:27Z
dc.date.available2020-01-14T16:36:27Z
dc.date.created2019-11-14T10:20:19Z
dc.date.issued2019
dc.identifier.citationFrontiers in Computational Neuroscience, 2019, 13:66nb_NO
dc.identifier.issn1662-5188
dc.identifier.urihttp://hdl.handle.net/11250/2636281
dc.description.abstractPyramidal cells in layer V of the neocortex are one of the most widely studied neuron types in the mammalian brain. Due to their role as integrators of feedforward and cortical feedback inputs, they are well-positioned to contribute to the symptoms and pathology in mental disorders—such as schizophrenia—that are characterized by a mismatch between the internal perception and external inputs. In this modeling study, we analyze the input/output properties of layer V pyramidal cells and their sensitivity to modeled genetic variants in schizophrenia-associated genes. We show that the excitability of layer V pyramidal cells and the way they integrate inputs in space and time are altered by many types of variants in ion-channel and Ca2+ transporter-encoding genes that have been identified as risk genes by recent genome-wide association studies. We also show that the variability in the output patterns of spiking and Ca2+ transients in layer V pyramidal cells is altered by these model variants. Importantly, we show that many of the predicted effects are robust to noise and qualitatively similar across different computational models of layer V pyramidal cells. Our modeling framework reveals several aspects of single-neuron excitability that can be linked to known schizophrenia-related phenotypes and existing hypotheses on disease mechanisms. In particular, our models predict that single-cell steady-state firing rate is positively correlated with the coding capacity of the neuron and negatively correlated with the amplitude of a prepulse-mediated adaptation and sensitivity to coincidence of stimuli in the apical dendrite and the perisomatic region of a layer V pyramidal cell. These results help to uncover the voltage-gated ion-channel and Ca2+ transporter-associated genetic underpinnings of schizophrenia phenotypes and biomarkers.nb_NO
dc.language.isoengnb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleComputational Modeling of Genetic Contributions to Excitability and Neural Coding in Layer V Pyramidal Cells: Applications to Schizophrenia Pathologynb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.volume13nb_NO
dc.source.journalFrontiers in Computational Neurosciencenb_NO
dc.identifier.doi10.3389/fncom.2019.00066
dc.identifier.cristin1747423
cristin.unitcode192,0,0,0
cristin.unitnameNorges miljø- og biovitenskapelige universitet
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
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