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A novel cortico-intrathalamic circuit for flight behavior

Nature Neuroscience volume 22, pages 941–949 (2019)Cite this article

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Abstract

Flight, an active fear response to imminent threat, is dependent on the rapid risk assessment of sensory information processed by the cortex. The thalamic reticular nucleus (TRN) filters information between the cortex and the thalamus, but whether it participates in the regulation of flight behavior remains largely unknown. Here, we report that activation of parvalbumin-expressing neurons in the limbic TRN, but not those in the sensory TRN, mediates flight. Glutamatergic inputs from the cingulate cortex (Cg) selectively activate the limbic TRN, which in turn inhibits the intermediodorsal thalamic nucleus (IMD). Activation of this Cg→limbic TRN→IMD circuit results in inhibition of the IMD and produces flight behavior. Conversely, removal of inhibition onto the IMD results in more freezing and less flight, suggesting that the IMD may function as a pro-freeze center. Overall, these findings reveal a novel corticothalamic circuit through the TRN that controls the flight response.

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Fig. 1: Activity of PV+ neurons in the limbic TRN, but not those in the sensory TRN, is tightly coupled with the onset of flight behavior.
Fig. 2: PV+ neurons in the limbic TRN, but not those in the sensory TRN, mediate flight.
Fig. 3: Glutamatergic inputs from the Cg to the limbic TRN mediate flight behavior.
Fig. 4: An inhibitory pathway from the limbic TRN to the IMD induces flight behavior.
Fig. 5: The Cg→limbic TRN→IMD circuit regulates flight behavior.

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Data availability

All relevant data supporting the present study are available from the lead corresponding author upon reasonable request.

Code availability

All relevant codes supporting the present study are available from the lead corresponding author upon reasonable request.

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Acknowledgements

The authors thank J. Hu (Shanghai Technology University, China) for providing the AAV2/9-EF1a-DIO-mGFP virus, E. J. Kremer (IGMM, Montpellier, France) for providing the CAV virus, L. Luo (Stanford, CA, USA) for providing the Flp-dependent AAV helpers. This work was supported by the National Natural Science Foundation of China (grant nos. 31430034, 31871070, and 91432306), the National Key Research and Development Plan of the Ministry of Science and Technology of China (grant no. 2016YF0501000), the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (grant nos. 2017PT31038 and 2018PT31041), Funds for Creative Research Groups of China from the National Natural Science Foundation of China (grant no. 81521062), the Program for Changjiang Scholars and Innovative Research Team in University, and the programme of introducing talents of discipline to universities (grant no. B13026) to X.-M.L.

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  1. These authors contributed equally: Ping Dong, Hao Wang.

Authors and Affiliations

  1. Center for Neuroscience and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Ping Dong, Hao Wang, Xiao-Fan Shen, Ping Jiang, Yue Li, Jia-Hao Gao, Shan Lin, Yue Huang, Shumin Duan, Hong Lian, Hao Wang, Jiadong Chen & Xiao-Ming Li

  2. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China

    Xu-Tao Zhu, Xiao-Bin He & Fu-Qiang Xu

  3. NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China

    Xiao-Ming Li

  4. Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Hangzhou, China

    Xiao-Ming Li

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Contributions

P.D. and X.-M.L. designed the project, and P.D. and H.W. performed virus or drug injections, optogenetic behavior, and electrophysiology experiments, and collected and analyzed the data. X.-T.Z. and J.-H.G. helped collect the data. P.D., P.J., X.-F.S., S.L., and Y.H. performed immunohistochemistry and quantitatively analyzed the imaging data. X.-B.H. generated RV and pseudo-RV, and F.-Q.X. supervised the retrograde virus labeling experiments. P.D., Y.L., J.C., S.D., H.W., and X.-M.L. interpreted the results and commented on the manuscript. P.D., H.W., H.L., J.C., and X.-M.L. wrote or edited the manuscript. X.-M.L. supervised all aspects of the project.

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Correspondence to Xiao-Ming Li.

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The authors declare no competing interests.

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Journal peer review information: Nature Neuroscience thanks Laszlo Acsady, Wulf Haubensak, and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figures 1–16

Reporting Summary

Supplementary Video 1

Fiber photometry recording of limbic TRN PV+ neurons during conditioned flight behavior. A representative trial of conditioned flight behavior in day 3 during fiber photometry recording.

Supplementary Video 2

Inhibition of limbic TRN PV+ neurons during conditioned flight behavior. Optogenetic inhibition of limbic TRN PV+ neurons decrease flight behavior.

Supplementary Video 3

Optogenetic activation of limbic TRN PV+ neurons during conditioned flight behavior. Optogenetic activation of limbic TRN PV+ neurons induce flight behavior.

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Dong, P., Wang, H., Shen, XF. et al. A novel cortico-intrathalamic circuit for flight behavior. Nat Neurosci 22, 941–949 (2019). https://doi.org/10.1038/s41593-019-0391-6

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