Corticotropin-releasing factor receptor 1 in infralimbic cortex modulates social stress-altered decision-making

Chronic stress could lead to a bias in behavioral strategies toward habits. However, it remains unclear which neuronal system modulates stress-induced behavioral abnormality during decision making. The corticotropin-releasing factor (CRF) system in the medial prefrontal cortex (mPFC), which has been implicated in governing strategy choice, is involved in the response to stress. The present study aimed to clarify whether altered function in cortical CRF receptors is linked to abnormal behaviors after chronic stress. In results, mice subjected to a 10-day social defeat preferred to use a habitual strategy. The infralimbic cortex (IL), but not the prelimbic cortex (PL) or anterior cingulate cortex (ACC), showed higher cFos expression in stress-subjected mice than in control mice, which may be associated with habitual behavior choice. Furthermore, CRF receptor 1 (CRFR1) agonist and antagonist infusion in IL during behavioral training mimicked and rescued stress-caused behavioral change in the decision-making assessment, respectively. An electrophysiological approach showed that the frequencies of both spontaneous IPSC and spontaneous EPSC, but not their amplitude, increased after stress and were modulated by CRFR1 agents. Further recordings revealed that an increased ratio of excitation to inhibition (E/I ratio) of IL by stress was rescued under conditions with CRFR1 antagonist. Collectively, these data indicate that CRFR1 plays a critical role in stress-permitted or enhanced glutamatergic and GABAergic presynaptic transmission in direct or indirect ways, as well as the modulation for E/I ratio in the IL. Thus, CRFR1 in the mPFC may be a proper target for treating cases of chronic stress-altered behavior.