A subthalamo-parabrachial glutamatergic pathway is involved in stress-induced self-grooming in mice

Tao Jia1, Jing Chen1, Ying-di Wang1, Cheng Xiao1,2,3, Chun-yi Zhou1,2,3
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
Correspondence to: Cheng Xiao:, Chun-yi Zhou:,
DOI: 10.1038/s41401-023-01114-6
Received: 14 December 2022
Accepted: 18 May 2023
Advance online: 15 June 2023


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.

Keywords: stress; emotional disorders; self-grooming; subthalamic nucleus; lateral parabrachial nucleus; glutamatergic neurons

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