Abstract
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.
Original language | English (US) |
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Pages (from-to) | 875-891 |
Number of pages | 17 |
Journal | Cerebral Cortex |
Volume | 29 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2019 |
Externally published | Yes |
Keywords
- forward modeling of EEG
- functional genomics
- ion channels
- multicompartmental neuron modeling
- schizophrenia genetics
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience