Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

Area of Science:

• Neuroscience
• Psychiatry
• Computational Neuroscience

Background:

• Working memory deficits are a core symptom of schizophrenia.
• Prefrontal cortex (PFC) dysfunction is implicated, but underlying neural circuits are unclear.

Purpose of the Study:

• Assess working memory in a chronic phencyclidine (PCP) mouse model.
• Identify neural substrates of working memory deficits.

Main Methods:

• Chronic PCP administration followed by withdrawal.
• T-maze task for working memory assessment.
• Brain-wide c-Fos mapping to identify neural activity.

Main Results:

• PCP-treated mice showed impaired working memory performance.
• Increased c-Fos+ cells in prelimbic cortex layer 2-3 during working memory effort.
• Altered neural activity in anterior cingulate, infralimbic cortex, and ventral hippocampus.

Conclusions:

• Chronic PCP treatment models schizophrenia-related working memory deficits.
• Layer 2-3 of the prelimbic cortex is crucial for working memory.
• Identified neural networks provide insights into PFC dysfunction in schizophrenia.