mGluR5 in hippocampal CA1 pyramidal neurons mediates stress-induced anxiety-like behavior

作者：Li, Xin; Du, Zhuo-Jun; Xu, Jun-Nan; Liang, Zhi-Man; Lin, Song; Chen, Hao; Li, Shu-Ji; Li, Xiao-Wen; Yang, Jian-Ming; Gao, Tian-Ming^*

来源：Neuropsychopharmacology, 2023, 48(8): 1164-1174.

DOI：10.1038/s41386-023-01548-w

• GLUTAMATE-RECEPTOR 5
• ANTAGONIST 2-METHYL-6-(PHENYLETHYNYL)PYRIDINE
• VENTRAL HIPPOCAMPUS
• SYNAPTIC STRENGTH
• EXPRESSION
• EXCITABILITY
• DISORDERS
• NETWORK
• DORSAL

Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for anxiety disorders. Nevertheless, the mechanism underlying the mGluR5 involvement in stress-induced anxiety-like behavior remains largely unknown. Here, we found that chronic restraint stress induced anxiety-like behavior and decreased the expression of mGluR5 in hippocampal CA1. Specific knockdown of mGluR5 in hippocampal CA1 pyramidal neurons produced anxiety-like behavior. Furthermore, both chronic restraint stress and mGluR5 knockdown impaired inhibitory synaptic inputs in hippocampal CA1 pyramidal neurons. Notably, positive allosteric modulator of mGluR5 rescued stress-induced anxiety-like behavior and restored the inhibitory synaptic inputs. These findings point to an essential role for mGluR5 in hippocampal CA1 pyramidal neurons in mediating stress-induced anxiety-like behavior.

• 单位
  南方医科大学