Zona incerta GABAergic neurons integrate prey-related sensory signals and induce an appetitive drive to promote hunting

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The neural substrates for predatory hunting, an evolutionarily conserved appetitive behavior, remain largely undefined. Photoactivation of zona incerta (ZI) GABAergic neurons strongly promotes hunting of both live and artificial prey. Conversely, photoinhibition of these neurons or deletion of their GABA function severely impairs hunting. Here electrophysiological recordings reveal that ZI neurons integrate prey-related multisensory signals and discriminate prey from non-prey targets. Visual or whisker sensory deprivation reduces calcium responses induced by prey introduction and attack and impair hunting. ZI photoactivation largely corrects the hunting impairment caused by sensory deprivations. Motivational and reinforcing assays reveal that ZI photoactivation is associated with a strong appetitive drive, causing repetitive self-stimulatory behaviors. These ZI neurons project to the periaqueductal gray matter to induce hunting and motivation. Thus, we have delineated the function of ZI GABAergic neurons in hunting, which integrates prey-related sensory signals into prey detection and attack and induces a strong appetitive motivational drive.

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Fig. 1: Photoactivation of ZIm GABAergic neurons promotes predatory hunting.
Fig. 2: Requirement of ZIm GABAergic neurons and GABA in predatory hunting.
Fig. 3: ZIm neurons are sensitive to hunting-related signals.
Fig. 4: ZI GABAergic neurons incorporate sensory signals into hunting.
Fig. 5: ZIm GABAergic neurons induce an appetitive motivational drive.
Fig. 6: ZIm GABAergic projections to the PAG promote hunting.

Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Code availability

The code that supports the findings of this study is available from the corresponding authors upon reasonable request.


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The authors thank the following individuals: M. Luo, H. Hu, C. Zhan, J. Liao, H. Zhu and Y. Zou for sharing reagents; X. Li and the Molecular Imaging Core Facility (MICF) of the School of Life Science and Technology, ShanghaiTech University, for microscopy imaging; Y. Xiong and the Molecular Cellular Core for slices and staining; all members of the Shen Lab and the “Shen Xian Hui (NPC)” Wechat group for valuable discussion. The authors also thank staff members from the Shanghai Model Organisms Center and Animal Facility at NFPS, Zhangjiang Lab, China. This study is funded by the National Natural Science Foundation of China (no. 91857104 and no. 31771169 to W.L.S.; no. 91432107 and no. 31671105 to H.L.), the Shanghai Municipal Education Commission (no. 2019-01-07-00-10-E00058 to W.L.S.), the Science Fund for Creative Research Group of China (no. 61721092 to H.L.), the Director Fund of the Wuhan National Laboratory for Optoelectronics (to H.L.), the Thousand Young Talents Program of China (to W.L.S.), the Shanghai Pujiang Talent Award (no. 2018X0302-101-01 to W.S.) and the ShanghaiTech University start-up fund (to W.L.S.).

Author information

Z.-D.Z., Zongming C., X.X. and M.H. performed most of the experiments. H.X., X.J., L.Q., C.S. and Y.Y. performed the behavioral evaluations. J.L. and X.N. performed the immunostaining. F.C. and Zijun C. performed the electrophysiology. Y.C. performed the multichannel recordings. Z.-D.Z., J.H., W.S., P.C., H.L. and W.L.S. designed the experiments. Z.-D. Z., Zongming C., M.H., H.L. and W.L.S. wrote the manuscript.

Correspondence to Haohong Li or Wei L. Shen.

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The authors declare no competing interests.

Additional information

Journal peer review information: Nature Neuroscience thanks Jennifer Hoy, Daesoo Kim and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Figures 1–25 and Supplementary Tables 1–3.

Reporting Summary

Supplementary Video 1

Home-cage behaviors. This video shows that photoactivation of zona incerta GABAergic neurons (ZImVgat-ChIEF) in food-supplied home-cages induces undirected-gnawing, biting objects, or binge-like eating. (Behavioral definitions: undirected gnawing, mice executed fictive-eating or gnawing uneatable bedding materials or feces; binge-like eating, mice rapidly bit and consumed food pellets; biting objects, mice bit on the food container or water nozzle.)

Supplementary Video 2

Photoactivation-induced bite attack. This video shows that one pulse of 100-ms photoactivation of zona incerta GABAergic neurons is sufficient to induce a bite attack on bedding materials.

Supplementary Video 3

ZI glutamatergic neurons did not promote hunting. This video shows that photoactivation of zona incerta glutamatergic neurons does not induce attacking, gnawing or eating of food or bedding materials.

Supplementary Video 4

Hunting of adult crickets. This video shows that adult crickets are very defensive and that photoactivation of zona incerta GABAergic neurons promotes hunting of adult crickets.

Supplementary Video 5

Attacking of artificial prey. This video shows that photoactivation of zona incerta GABAergic neurons elicits attacking of artificial prey.

Supplementary Video 6

Hunting behaviors of cricket-naive mice. This video shows that photoactivation of zona incerta GABAergic neurons increases attacking frequency in cricket-naive mice.

Supplementary Video 7

Photoactivation did not induce aggression. This video shows that photoactivation of zona incerta GABAergic neurons does not evoke attacking of male and female mice.

Supplementary Video 8

Photoinhibition interrupted hunting and eating. This video shows that photoinhibition of zona incerta GABAergic neurons in ZImVgat-GtACR mice abolishes cricket attacking, and eating.

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