Hypothalamic-hindbrain circuit for consumption-induced fear regulation

Qin Wang, Rui-Yue Sun, Jia-Xue Hu, Yan-Hui Sun, Chun-Yue Li, Huiqian Huang, Hao Wang () and Xiao-Ming Li ()
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Qin Wang: Zhejiang University School of Medicine
Rui-Yue Sun: Zhejiang University School of Medicine
Jia-Xue Hu: Zhejiang University School of Medicine
Yan-Hui Sun: Zhejiang University School of Medicine
Chun-Yue Li: Zhejiang University School of Medicine
Huiqian Huang: Zhejiang University School of Medicine
Hao Wang: Zhejiang University School of Medicine
Xiao-Ming Li: Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.

Date: 2024
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DOI: 10.1038/s41467-024-51983-6

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