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Inhibitory gain modulation of defense behaviors by zona incerta

Author

Listed:
  • Xiao-lin Chou

    (University of Southern California
    University of Southern California)

  • Xiyue Wang

    (University of Southern California
    University of Southern California)

  • Zheng-gang Zhang

    (University of Southern California
    Southern Medical University)

  • Li Shen

    (University of Southern California)

  • Brian Zingg

    (University of Southern California
    University of Southern California)

  • Junxiang Huang

    (University of Southern California
    University of Southern California)

  • Wen Zhong

    (University of Southern California
    Southern Medical University)

  • Lukas Mesik

    (University of Southern California
    University of Southern California)

  • Li I. Zhang

    (University of Southern California
    University of Southern California)

  • Huizhong Whit Tao

    (University of Southern California
    University of Southern California)

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.

Suggested Citation

  • Xiao-lin Chou & Xiyue Wang & Zheng-gang Zhang & Li Shen & Brian Zingg & Junxiang Huang & Wen Zhong & Lukas Mesik & Li I. Zhang & Huizhong Whit Tao, 2018. "Inhibitory gain modulation of defense behaviors by zona incerta," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03581-6
    DOI: 10.1038/s41467-018-03581-6
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    Cited by:

    1. Sandeep Sharma & Cecilia A. Badenhorst & Donovan M. Ashby & Stephanie A. Vito & Michelle A. Tran & Zahra Ghavasieh & Gurleen K. Grewal & Cole R. Belway & Alexander McGirr & Patrick J. Whelan, 2024. "Inhibitory medial zona incerta pathway drives exploratory behavior by inhibiting glutamatergic cuneiform neurons," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Fernando M. C. V. Reis & Sandra Maesta-Pereira & Matthias Ollivier & Peter J. Schuette & Ekayana Sethi & Blake A. Miranda & Emily Iniguez & Meghmik Chakerian & Eric Vaughn & Megha Sehgal & Darren C. T, 2024. "Control of feeding by a bottom-up midbrain-subthalamic pathway," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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