SCZ-associated variant effects on L5 pyr cell NN activity and delta osc. (Maki-Marttunen et al 2018)


" … 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 decit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia."

Model Type: Neuron or other electrically excitable cell

Region(s) or Organism(s): Neocortex

Cell Type(s): Neocortex L5/6 pyramidal GLU cell

Currents: Ca pump; I A, slow; I h; I K; I K,Ca; I K,leak; I L high threshold; I M; I Na,p; I Na,t; I T low threshold

Receptors: AMPA; NMDA; Gaba

Genes: Cav1.2 CACNA1C; Cav1.3 CACNA1D; Cav3.3 CACNA1I; HCN1; Kv2.1 KCNB1; Nav1.1 SCN1A; PMCA ATP2B2

Transmitters: Glutamate; Gaba

Model Concept(s): Schizophrenia; Oscillations

Simulation Environment: NEURON; Python; LFPy

Implementer(s): Maki-Marttunen, Tuomo [tuomomm at uio.no]

References:

Mäki-Marttunen T et al. (2019). Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations. Cerebral cortex (New York, N.Y. : 1991). 29 [PubMed]


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