Schizophrenia is a severe mental disorder with cognitive dysfunction as one of the core symptoms. Piccolo encoded by the PCLO gene serves at the nerve terminal, its knock down (KD) in mice prefrontal cortex (PFC) induced schizophrenia-like symptoms. The animal model shows cognitive dysfunction, however the mechanism has not been clarified. In this study, we investigated the role of the Piccolo in the perirhinal cortex (PRC) in cognitive function, since of bidirectional connections between the PFC and HIP via the PRC involved in memory consolidation.
AAV-miPCLO/GFP vectors was injected into the mice PRC (PRC-Piccolo-KD), and were assessed by behavioral and electrophysiological tests. PRC-Piccolo-KD mice showed memory impairments in the several tasks. Directional projection from PRC to ventral HIP was observed using GFP searching. LTP in the ventral HIP decreased in the PRC-Piccolo-KD mice.
Our findings suggest that Piccolo in the PRC plays an important role in synaptic plasticity in the ventral HIP via functional deficits of the PFC-PRC-HIP pathway, leading to schizophrenia-like cognitive dysfunction. Modulation of Piccolo in PRC will be a target for therapeutic approaches to schizophrenia-like cognitive dysfunction.