The involvement of phosphatidylinositol system in a rat model of schizophrenia

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First we examined the effect of SKF83959, Phosphatidylinositol-linked D1 receptor agonist, on synaptic transmission in CA1 area of mouse hippocampus. Spontaneous inhibitory postsynaptic currents recorded on pyramidal cells was enhanced by SKF83959.Then we decided to utilize'social isolation model'(SI-model) mice as a schizophrenia animal model. In behavioral tests, the reduction of prepulse inhibition and the decrease of percent alteration in Y-maze task were revealed, and we accepted these mice as schizophrenia animal model. Next we performed the electrophysiological recording to clarify certain abnormalities in a local neural circuit of SI-model mice. We recorded excitatory postsynaptic currents(EPSCs) and inhibitory postsynaptic currents(IPSCs) from pyramidal cells in layer 5 of mouse prefrontal cortex. The frequencies of the both spontaneous EPSCs and miniature EPSCs were lower in SI-model mice than control mice, whereas there was no significant difference between SI-model and control in spontaneous IPSCs. However, as we hypothesize alterations of the excitability of GABAergic interneurons, we next plan to directly record from interneurons to detect alterations of the membrane property. Following the comprehensive identification of the abnormalities of neural circuits in SI-model mouse, we plan to examine the therapeutic response of chronic administration of SKF83959 against aberrant neural circuits in SI-model mice PFC.