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作 者:Tao Jia Jing Chen Ying-di Wang Cheng Xiao Chun-yi Zhou
机构地区:[1]Jiangsu Province Key Laboratory in Anesthesiology,School of Anesthesiology,Xuzhou Medical University,Xuzhou,221004,China [2]Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology,Xuzhou Medical University,Xuzhou,221004,China [3]NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs,School of Anesthesiology,Xuzhou Medical University,Xuzhou,221004,China
出 处:《Acta Pharmacologica Sinica》2023年第11期2169-2183,共15页中国药理学报(英文版)
基 金:supported by the National Natural Science Foundation of China 81971038(CYZ),82071231(CX),82171235(CYZ),82271293(CX),81870891(CX);the Fund for Jiangsu Province Specially-Appointed Professor(CX,CYZ),the Natural Science Foundation of Jiangsu Province(BK20211349,CYZ);the Leadership Program in Xuzhou Medical University(JBGS202203,CX);TJ and JC acknowledge the Postgraduate Innovation Program in Jiangsu Province(KYCX22_2936,KYCX22_2952).
摘 要:Excessive self-grooming is an important behavioral phenotype of the stress response in rodents. Elucidating the neural circuit that regulates stress-induced self-grooming may suggest potential treatment to prevent maladaptation to stress that is implicated in emotional disorders. Stimulation of the subthalamic nucleus (STN) has been found to induce strong self-grooming. In this study we investigated the role of the STN and a related neural circuit in mouse stress-related self-grooming. Body-restraint and foot-shock stress-induced self-grooming models were established in mice. We showed that both body restraint and foot shock markedly increased the expression of c-Fos in neurons in the STN and lateral parabrachial nucleus (LPB). Consistent with this, the activity of STN neurons and LPB glutamatergic (Glu) neurons, as assessed with fiber photometry recording, was dramatically elevated during self-grooming in the stressed mice. Using whole-cell patch-clamp recordings in parasagittal brain slices, we identified a monosynaptic projection from STN neurons to LPB Glu neurons that regulates stress-induced self-grooming in mice. Enhanced self-grooming induced by optogenetic activation of the STN-LPB Glu pathway was attenuated by treatment with fluoxetine (18 mg·kg^(−1)·d^(−1), p.o., for 2 weeks) or in the presence of a cage mate. Furthermore, optogenetic inhibition of the STN-LPB pathway attenuated stress-related but not natural self-grooming. Taken together, these results suggest that the STN-LPB pathway regulates the acute stress response and is a potential target for intervention in stress-related emotional disorders.
关 键 词:STRESS emotional disorders SELF-GROOMING subthalamic nucleus lateral parabrachial nucleus glutamatergic neurons
分 类 号:R742.5[医药卫生—神经病学与精神病学]
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