Abstract
Piccolo, a presynaptic protein, plays a role in synaptic vesicle trafficking of neurotransmission process. Previous studies have revealed that the Piccolo‐coding gene PCLO were associated with psychiatric disorders. However, few studies are available on the causal relationship between Piccolo dysfunction and psychosis symptoms in vivo. Accordingly, phenotypes in mice with suppression of Piccolo in the medial prefrontal cortex (mPFC) were evaluated. Piccolo‐suppressed mice showed hyperlocomotion in a novel environment, impaired prepulse inhibition and decreased cognitive function. These behaviors were partially ameliorated by atypical antipsychotic drug. The mice exposed to mild social defeat stress exhibited additional social withdrawal and behavioral despair. Furthermore, synaptic plasticity in the mPFC and glutamatergic and dopaminergic neurotransmission by activating mPFC projection in the dorsal striatum were inhibited in Piccolo‐suppressed mice. These observations suggest that disconnection with the mPFC pathway via suppression of Piccolo mediates schizophrenia symptoms, e. g. positive and negative symptoms and cognitive deficit.
