Effects of CUMS on excitatory/inhibitory balance of hippocampal and prefrontal cortex pyramidal neurons in anxiety-like mice

Abstract

Objective: To explore the changes in the excitatory/inhibitory (E/I) balance of pyramidal neurons in prefrontal cortex and hippocampus in mice with anxiety disorder induced by chronic unpredictable mild stress (CUMS). Methods: Twenty-four C57/BL6 male mice were randomly divided into control group (CTRL) and model group (CUMS), with 12 mice in each group. The mice in CUMS group were subjected to 21 days of stress, including restraint for 1 h, reversed day/night cycle for 24 h, forced warm water bath for 5 min, water/food deprivation for 24 h, housing in wet sawdust for 18 h, shaking the cage for 30 min, noise for 1 h, and social stress for 10 min. CTRL group mice were fed normally. Anxiety-related behavioral tests and whole-cell recording tests were performed after modeling. Results: Compared with CTRL group, the time of spent in the central arena of CUMS group was reduced significantly in open field test (P＜0.01), the time and number of entering the open arms were decreased significantly in elevated plus maze test (P＜0.01), and the time of staying in the closed arms was increased significantly in CUMS group (P＜0.01). The sEPSC frequency, capacitance and E/I ratio of dlPFC, mPFC and vCA1 pyramidal neurons of mice in CUMS group were increased significantly (P＜0.01), while sEPSC amplitude, sIPSC frequency, amplitude and capacitance were not significantly changed (P＞0.05). The frequency, amplitude, capacitance and E/I ratio of sEPSC and sIPSC of dCA1 pyramidal neurons were not significantly changed (P＞0.05). Conclusion: The anxiety-like behavior of CUMS-induced mice may be the result of the participation of multiple brain regions, which is mainly related to the increase of the excitability of pyramidal neurons in dlPFC, mPFC and vCA1 brain regions, but seems to have little relationship with dCA1 brain regions.