Cerebellin-2 positive (Cbln2+) Neurons in the Parafascicular Thalamic Nucleus Regulate Self-Grooming Behavior

Zhang, L.; Song, H.; Li, Y.; Zhang, H.; Geng, D.; Zhao, Z.; Yang, B.; Zheng, R.; Li, Z.; Wang, L.; Zhang, T.; Xie, Z.; Cao, P.; Li, D.; Zhang, F.

doi:10.1101/2025.03.22.644777

bioRxiv · 10.1101/2025.03.22.644777

Cerebellin-2 positive (Cbln2+) Neurons in the Parafascicular Thalamic Nucleus Regulate Self-Grooming Behavior

Zhang, L.·Song, H.·Li, Y.·Zhang, H.·Geng, D.·Zhao, Z.·Yang, B.·Zheng, R.·Li, Z.·Wang, L.·Zhang, T.·Xie, Z.·Cao, P.·Li, D.·Zhang, F.

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Abstract

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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Zhang, L., Song, H., Li, Y., Zhang, H., Geng, D., Zhao, Z., Yang, B., Zheng, R., Li, Z., Wang, L., Zhang, T., Xie, Z., Cao, P., Li, D., Zhang, F.. 2025-03-24. Cerebellin-2 positive (Cbln2+) Neurons in the Parafascicular Thalamic Nucleus Regulate Self-Grooming Behavior. https://doi.org/10.1101/2025.03.22.644777

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