Whole-brain Mapping of Inputs and Outputs of Specific Orbitofrontal Cortical Neurons in Mice

 Yijie Zhang1,2 · Wen Zhang1  · Lizhao Wang1  · Dechen Liu1  · Taorong Xie1  · Ziwei Le1,2 · Xiangning Li3  · Hui Gong3,4  · Xiao‑Hong Xu1,5  · Min Xu1,5  · Haishan Yao1,5,6
1 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 
2 University of Chinese Academy of Sciences, Beijing 100049, China 
3 HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215123, China 
4 CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 
5 Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China 
6 Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, Shanghai 200031, China

Abstract
The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.

Keywords
Orbitofrontal cortex; Projection specifc; Rabies virus retrograde tracing; Anterograde transsynaptic virus tracing; Inhibitory neurons