Role of the Prefrontal Cortex in Altered Hippocampal-Accumbens Synaptic Plasticity in a Developmental Animal Model of Schizophrenia

摘要

Schizophrenia is characterized by alterations in cortico-limbic processes believed to involve modifications in activity within the prefrontal cortex (PFC) and the hippocampus. The nucleus accumbens (NAc) integrates information from these 2 brain regions and is involved in cognitive and psychomotor functions that are disrupted in schizophrenia, indicating an important role for this structure in the pathophysiology of this disorder. In this study, we used in vivo elec-trophysiological recordings from the NAc and the PFC of adult rats and the MAM developmental disruption rodent model of schizophrenia to explore the influence of the medial PFC on the hippocam-pal accumbens pathway. We found that, in MAM-treated rats, tetanization of hippocampal inputs to the NAc produce opposite synaptic plasticity compared with controls, which is a consequence of alterations in the hippocampal-mPFC pathway. Moreover, we show that administration of the D2-receptor-blocking antipsychotic drug sulpiride either systemically or directly into the mPFC reverses the alterations in the MAM rat. Therefore, specific disruptions in cortical and hippocampal inputs in the MAM-treated rat abnormally alter plasticity in subcortical structures. Moreover, our results suggest that, in the presence of antipsychotic drugs, the disrupted plasticities are normalized, supporting a role for this mechanism in antipsychotic drug action in schizophrenia.