Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The ventral hippocampus (vHPC) is central to affective and cognitive processing and displays a high density of acetylcholine (ACh) muscarinic receptors (mAChRs). However, the precise role of vHPC mAChRs in anxiety remains to be fully investigated. In this study, we found that chronic restraint stress (CRS) induced social avoidance and anxiety-like behaviors in mice and increased mAChR expression in the vHPC. CRS increased the vHPC ACh release in behaving mice. Moreover, CRS altered the synaptic activities and enhanced neuronal activity of the vHPC neurons. Using pharmacological and viral approaches, we showed that infusing the antagonist of mAChRs or decreasing their expression in the vHPC attenuated the anxiety-like behavior and rescued the social avoidance behaviors in mice probably due to suppression of vHPC neuronal activity and its excitatory synaptic transmission. Our results suggest that the changes of neuronal activity and synaptic transmission in the vHPC mediated by mAChRs may play an important role in stress-induced anxiety-like behavior, providing new insights into the pathological mechanism and potential pharmacological target for anxiety disorders.

慢性应激暴露会增加发生各种神经精神疾病的风险。腹侧海马（vHPC）是情感和认知过程的中心，并显示高密度的乙酰胆碱（ACh）毒蕈碱受体（mAChRs）。然而，vHPC mAChRs在焦虑中的确切作用仍有待充分研究。在这项研究中，我们发现慢性束缚应激（CRS）在小鼠中引起社交回避和焦虑样行为，并在vHPC中增加mAChR表达。CRS增加了行为小鼠的vHPC ACh释放。此外，CRS改变了vHPC神经元的突触活性和增强的神经元活性。使用药理学和病毒学方法，我们发现，注入mAChRs拮抗剂或降低其在vHPC中的表达可减轻小鼠的焦虑样行为，并挽救了小鼠的社交回避行为，这可能是由于vHPC神经元活性及其兴奋性突触传递受到抑制所致。我们的结果表明，mAChRs介导的vHPC中神经元活性和突触传递的变化可能在应激诱导的焦虑样行为中发挥重要作用，从而为焦虑症的病理机制和潜在药理学靶点提供了新见解。