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) |
|---|---|
| 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 |
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Keywords
- forward modeling of EEG
- functional genomics
- ion channels
- multicompartmental neuron modeling
- schizophrenia genetics
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience
Cite this
Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations. / Mäki-Marttunen, Tuomo; Krull, Florian; Bettella, Francesco; Hagen, Espen; Næss, Solveig; Ness, Torbjørn V.; Moberget, Torgeir; Elvsåshagen, Torbjørn; Metzner, Christoph; Devor, Anna; Edwards, Andrew G.; Fyhn, Marianne; Djurovic, Srdjan; Dale, Anders M.; Andreassen, Ole A.; Einevoll, Gaute T.
In: Cerebral Cortex, Vol. 29, No. 2, 01.02.2019, p. 875-891.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
AU - Mäki-Marttunen, Tuomo
AU - Krull, Florian
AU - Bettella, Francesco
AU - Hagen, Espen
AU - Næss, Solveig
AU - Ness, Torbjørn V.
AU - Moberget, Torgeir
AU - Elvsåshagen, Torbjørn
AU - Metzner, Christoph
AU - Devor, Anna
AU - Edwards, Andrew G.
AU - Fyhn, Marianne
AU - Djurovic, Srdjan
AU - Dale, Anders M.
AU - Andreassen, Ole A.
AU - Einevoll, Gaute T.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - forward modeling of EEG
KW - functional genomics
KW - ion channels
KW - multicompartmental neuron modeling
KW - schizophrenia genetics
UR - http://www.scopus.com/inward/record.url?scp=85059499086&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059499086&partnerID=8YFLogxK
U2 - 10.1093/cercor/bhy291
DO - 10.1093/cercor/bhy291
M3 - Article
C2 - 30475994
AN - SCOPUS:85059499086
VL - 29
SP - 875
EP - 891
JO - Cerebral Cortex
JF - Cerebral Cortex
SN - 1047-3211
IS - 2
ER -