Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway

•Cold swim, swim or elevation stress induced c-Fos in the rat nucleus incertus (NI).•These stressors also impaired hippocampo-medial prefrontal cortical (HP-mPFC) LTP.•Intra-NI infusion of antalarmin (specific CRF1 antagonist) prevented elevation stress-induced suppression of HP-mPFC LTP.•NI-HP-mPFC is a stress responsive circuit in rodents.

The nucleus incertus (NI) is a small cluster of brainstem neurons presumed to play a role in stress responses. We show that swim stress (normal water: 30 min and cold water: 20 min) and elevation stress robustly induced c-Fos expression in the NI and significantly suppressed long-term potentiation (LTP) in the hippocampo-medial prefrontal cortical (HP-mPFC) pathway. To examine whether activation of CRF1 receptors in the NI plays a role in the suppression of HP-mPFC LTP, antalarmin, a specific CRF1 receptor antagonist, was infused directly into the NI either before presentation of (1) elevation stress or (2) high frequency stimulation. As predicted, the intra-NI infusion of antalarmin reversed the elevation stress-induced suppression of LTP in the HP-mPFC pathway. This report suggests that the CRF1 receptor in the NI contributes to stress-related impairment in plasticity of the HP-mPFC pathway. The findings suggest that the NI-HP-mPFC is a stress responsive circuit in the rodent brain.