Stress resilient role of mGluR5 in BLA target neurons

초록

Metabotropic glutamate receptor 5 (mGluR5) has been implicated in stress responses and related psychiatric disorders. Here, we demonstrate that mGluR5, whose expression depends on the activity of basolateral amygdala (BLA) neurons projecting to the medial prefrontal cortex (BLAmPFC) or ventral hippocampus (BLAvHPC), promotes resilience to chronic social defeat stress (CSDS). We observed that CSDS disrupts glutamatergic transmission in the BLAmPFC and BLAvHPC circuits, the activity of which is dysregulated by CSDS. Photomodulation of these circuits reversed the detrimental effects of CSDS on social behaviors and mGluR5 expression in the mPFC and vHPC. Viral-mediated mGluR5 modulation also contributed to CSDS-associated behavioral plasticity, indicating a pro-resilient role of mGluR5. Furthermore, we found that pro-resilience effects are mediated through distinctive mGluR5 downstream signaling pathways in the mPFC and vHPC. Together, these data identify mGluR5 as a critical mediator of stress resilience, highlighting circuit-specific downstream signaling for depressive-like social impairment.