Corticosterone is a stress hormone, which is often associated with a variety of the central nervous system diseases. The study was to investigate the effects of Chronic corticosterone exposure (CCE) on the alteration of neural oscillatory patterns which supported a wide range of basic and higher cognitive activities, and a potential mechanism. Accordingly, a chronic corticosterone exposure model was established in C57BL mice. Behavioral experiments showed that emotion regulation and short-term working memory were significantly impaired in CCE mice. Neural oscillation analysis showed that the increase of corticosterone reduced the theta-band energy but increased the gamma-band energy in the hippocampus dentate gyrus (DG) region. Moreover, the theta rhythm synchronization between perforant path (PP) and DG, and the strength of theta-gamma cross-frequency coupling were significantly attenuated in CCE mice. Meanwhile, CCE treatment could inhibit the expression of PSD95, SYP and NMDAR2A/B and increased the expression of GAD67 and GABAR. These results suggest that CCE may lead to emotion regulation and short-term working memory dysfunction through disturbing neural activity patterns, which was closely associated with disrupting the excitatory-inhibitory balance.
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