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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 | Huizhong Whit Tao
Nature communications | 2018

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.

Pubmed ID: 29559622

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: U01 NS103558
  • Agency: NEI NIH HHS, United States
    Id: R21 EY022478
  • Agency: NIDCD NIH HHS, United States
    Id: R01 DC008983
  • Agency: NEI NIH HHS, United States
    Id: R01 EY019049
  • Agency: NIDCD NIH HHS, United States
    Id: F31 DC015185
  • Agency: NIMH NIH HHS, United States
    Id: RF1 MH114112

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