Whole-Brain Connectome of GABAergic Neurons in the Mouse Zona Incerta

 Yang Yang1  · Tao Jiang2  · Xueyan Jia2  · Jing Yuan1,2 · Xiangning Li1,2 · Hui Gong1,2
1 Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, China 
2 Research Unit of Multimodal Cross Scale Neural Signal Detection and Imaging, Chinese Academy of Medical Sciences, HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215123, China

Abstract
The zona incerta (ZI) is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation. However, the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped. Here, we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing. The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized. The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors, while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus. Clustering results show that the medial and lateral ZI are two different major functional compartments, and they can be further divided into more subdomains based on projection and input connectivity. This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information, conveying motivational states, and modulating global behaviors.

Keywords
Zona incerta; GABAergic neurons; Whole-brain connectome; Input circuit; Output circuit; Topological connection