Transcriptomic and spatial GABAergic neuron subtypes in zona incerta mediate distinct innate behaviors

• DOI: 10.1038/s41467-025-57896-2
• Publication Date: 2025-04-01T13:43:12Z
• Authors: Mengyue Zhu; Jieqiao Peng; Mi Wang; Shan Lin; Huiying Zhang; Yu Zhou; Xinyue Dai; Huiying Zhao; Yan-qin Yu; Li Shen; Xiao-Ming Li; Jiadong Chen
• Keywords: Zona incerta

Understanding the anatomical connection and behaviors of transcriptomic neuron subtypes is critical to delineating cell type-specific functions in the brain. Here we integrated single-nucleus transcriptomic sequencing,in vivocircuit mapping, optogenetic and chemogenetic approaches to dissect the molecular identity and function of heterogeneous GABAergic neuron populations in the zona incerta (ZI) in mice, a region involved in modulating various behaviors. By microdissecting ZI for transcriptomic and spatial gene expression analyses, our results revealed two non-overlappingEcel1-andPde11a-expressing GABAergic neurons with dominant expression in the rostral and medial zona incerta (ZIrEcel1and ZImPde11a), respectively. The GABAergic projection from ZIrEcel1to periaqueductal gray mediates self-grooming, while the GABAergic projection from ZImPde11ato the oral part of pontine reticular formation promotes transition from sleep to wakefulness. Together, our results revealed the molecular markers, spatial organization and specific neuronal circuits of two discrete GABAergic projection neuron populations in segregated subregions of the ZI that mediate distinct innate behaviors, advancing our understanding of the functional organization of the brain.