[Social isolation induces social avoidance in mice: the mediating role of the medial prefrontal cortex glutamatergic neurons].

OBJECTIVES

To investigate social isolation (SI)-induced abnormal behaviors and changes in neuronal activity in the medial prefrontal cortex (mPFC) of mice.

METHODS

Male C57BL/6J mice kept under normal conditions or SI mice housed in individual cages for 2 weeks were subjected to intracerebral microinjection of a control virus, a chemogenetic activation virus, or an optogenetic activation virus (n=8). The mice were assessed for behavioral changes and examined for neuronal changes in mPFC using c-fos immunofluorescence staining and co-staining with specific antibodies against CaMKIIα (for excitatory neurons) and GABA (for inhibitory neurons). In vivo optical fiber recording was used to detect real-time neuronal changes in the mice during behavioral assessment. The effects of chemogenetics and optogenetics for modulating activities of glutamatergic neurons in the mPFC were observed on social behaviors of both the control and SI mice.

RESULTS

Behavioral tests showed that two weeks of SI did not cause obvious anxiety or depression-like behaviors or impair object recognition memory, working memory, social ability or social memory, but induced social avoidance behaviors in the mice. Immunofluorescence staining revealed significantly increased c-fos-positive neurons in the mPFC of SI mice, consisting mostly of excitatory glutamatergic neurons. In vivo optical fiber recording showed that during the second stage of social interaction test (SIT), the activity of mPFC glutamatergic neurons increased significantly in SI mice. Chemogenetic and optogenetic activation of mPFC glutamatergic neurons induced obvious social avoidance in the control mice, and inhibition of these neurons significantly alleviated social avoidance in SI mice.

CONCLUSIONS

Two weeks of SI can induce social avoidance behaviors in mice and enhances the activity of mPFC glutamatergic neurons.