Inhibitory gain modulation of defense behaviors by zona incerta

Xiao-lin Chou, Xiyue Wang, Zheng-gang Zhang, Li Shen, Brian Zingg, Junxiang Huang, Wen Zhong, Lukas Mesik, Li I. Zhang () and Huizhong Whit Tao ()
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Xiao-lin Chou: University of Southern California
Xiyue Wang: University of Southern California
Zheng-gang Zhang: University of Southern California
Li Shen: University of Southern California
Brian Zingg: University of Southern California
Junxiang Huang: University of Southern California
Wen Zhong: University of Southern California
Lukas Mesik: University of Southern California
Li I. Zhang: University of Southern California
Huizhong Whit Tao: University of Southern California

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation. ZIr activity progressively increases during extinction of conditioned freezing response, and suppressing ZIr activity impairs the expression of fear extinction. Furthermore, ZIr is innervated by the medial prefrontal cortex (mPFC), and silencing mPFC prevents the increase of ZIr activity during extinction and the expression of fear extinction. Together, our results suggest that ZIr is engaged in modulating defense behaviors.

Date: 2018
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DOI: 10.1038/s41467-018-03581-6

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