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September 2nd, 2025
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National Institute of Biological Sciences, Beijing, China. Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
neuroscience
bioRxiv

Cerebellin-2 neurons in the parafascicular thalamic nucleus regulate self-grooming behavior

Zhang, L.Open in Google Scholar•Song, H.Open in Google Scholar•Li, Y.Open in Google Scholar•Zhang, H.Open in Google Scholar•Geng, D.Open in Google Scholar•Zhao, Z.Open in Google Scholar•Yang, B.Open in Google Scholar•Zheng, R.Open in Google Scholar•Li, Z.Open in Google Scholar•Wang, L.Open in Google Scholaret al.

Self-grooming represents a stereotyped repetitive behavior which is commonly observed in various neuropsychiatric disorders. Deep brain stimulation (DBS) targeting the centromedian / parafascicular complex (CM/PF) has been shown to alleviate obsessive-compulsive disorder/behavior (OCD/OCB) symptoms in human. However, little is known about the neural circuits of the PF that are involved in the regulation of self-grooming behavior in rodents. Here, we report that cerebellin-2 positive (Cbln2+) neurons in PF bidirectionally encode self-grooming. Chemogenetic activation of Cbln2+ PF neurons significantly reduces both physiological and pathological self-grooming, and chemogenetic inhibition of Cbln2+ PF neurons increases physiological self-grooming. Moreover, activating synaptic excitatory inputs to Cbln2+ PF neurons inhibits self-grooming, while synaptic inhibitory inputs enhance it. Cbln2+ PF neurons independently transmit neural signals to the dorsal and ventral striatum. Activation of PF-dorsal striatum and PF-ventral striatum pathways both inhibit self-grooming behavior. Most excitingly, we alleviate excessive grooming in OCD mice by the activation of PF neurons using non-invasive ultrasound stimulation. Together, these data reveal that Cbln2+ PF neurons are integral components of a brain network involved in self-grooming behavior and highly promising targets in the non-invasive therapy of OCD.

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