MGlu2/3 receptors within the ventral part of the lateral septal nuclei modulate stress resilience and vulnerability in mice

Abstract

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs’ agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.