Correlation between abnormal hippocampal neural activities and spatial cognitive impairments in the model mice of schizophrenia and therapeutic effects of aripiprazole

Spatial cognitive-behavioral deficits represent core clinical symptoms of schizophrenia (SZ), yet their neurophysiological mechanisms and effective treatment strategies remain unclear. Previous research has indicated a reduction in hippocampal volume and weakened intercellular connectivity in SZ patients, but the causal link between these hippocampal abnormalities and spatial cognitive impairments is poorly defined. To investigate this relationship, we used a virtual spatial location (VSL) task and in vivo calcium imaging in MK-801-treated mice. Furthermore we evaluated the therapeutic effects of aripiprazole (ARI). Behavioral analyses revealed that MK-801-treated mice exhibited hyperactivity (increased locomotor distance and speed) and pronounced spatial working memory deficits. Calcium imaging in the hippocampal dorsal CA1 (dCA1) region demonstrated aberrant neuronal hyperactivity, characterized by elevated calcium signal frequency, amplitude, and half-width duration, alongside impaired neural synchronization and diminished encoding precision for spatial-reward associations. ARI treatment significantly mitigated these behavioral and neuronal abnormalities. These findings establish a direct correlation between MK-801-induced hippocampal excitatory dysregulation and spatial cognitive deficits, while highlighting ARI’s therapeutic potential in mitigating schizophrenia-related spatial cognitive-behavioral impairments.