Mei Li, Zhou Yu, Sun Yi, Liu Hong, Zhang Dengwen, Liu Pingping, Shu Haihua
Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Mol Neurosci. 2020 Dec 15;13:598811. doi: 10.3389/fnmol.2020.598811. eCollection 2020.
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.
长期暴露于应激会增加患各种神经精神疾病的风险。腹侧海马体（vHPC）在情感和认知加工中起核心作用，且表现出高密度的乙酰胆碱（ACh）毒蕈碱受体（mAChRs）。然而，vHPC mAChRs在焦虑中的精确作用仍有待充分研究。在本研究中，我们发现慢性束缚应激（CRS）在小鼠中诱导社交回避和焦虑样行为，并增加vHPC中mAChR的表达。CRS增加了行为小鼠的vHPC乙酰胆碱释放。此外，CRS改变了vHPC神经元的突触活动并增强了其神经元活动。使用药理学和病毒学方法，我们表明注入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社交回避行为，这可能是由于抑制了vHPC神经元活动及其兴奋性突触传递。我们的结果表明，由mAChRs介导的vHPC神经元活动和突触传递的变化可能在应激诱导的焦虑样行为中起重要作用，为焦虑症的病理机制和潜在药理学靶点提供了新的见解。
