Journal
CEREBRAL CORTEX
Volume 29, Issue 2, Pages 875-891Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhy291
Keywords
forward modeling of EEG; functional genomics; ion channels; multicompartmental neuron modeling; schizophrenia genetics
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Funding
- NIH [5 R01-EB000790-10]
- European Union Horizon 2020 Research and Innovation Programme [604102]
- Research Council of Norway [216699, 223273, 226971, 248778, 249711, 248828, 250128]
- South East Norway Health Authority [2017-112]
- KG Jebsen Stiftelsen
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Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.
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