Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice

Young Hee Lee, Yu-Been Kim, Kyu Sik Kim, Mirae Jang, Ha Young Song, Sang-Ho Jung, Dong-Soo Ha, Joon Seok Park, Jaegeon Lee, Kyung Min Kim, Deok-Hyeon Cheon, Inhyeok Baek, Min-Gi Shin, Eun Jeong Lee, Sang Jeong Kim and Hyung Jin Choi ()
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Young Hee Lee: Seoul National University College of Medicine
Yu-Been Kim: Seoul National University College of Medicine
Kyu Sik Kim: Seoul National University College of Medicine
Mirae Jang: Seoul National University College of Medicine
Ha Young Song: Seoul National University College of Medicine
Sang-Ho Jung: Seoul National University College of Medicine
Dong-Soo Ha: Seoul National University College of Medicine
Joon Seok Park: Seoul National University College of Medicine
Jaegeon Lee: Seoul National University College of Medicine
Kyung Min Kim: Seoul National University College of Medicine
Deok-Hyeon Cheon: Seoul National University College of Medicine
Inhyeok Baek: Seoul National University College of Medicine
Min-Gi Shin: Ajou University School of Medicine
Eun Jeong Lee: Ajou University School of Medicine
Sang Jeong Kim: Seoul National University College of Medicine
Hyung Jin Choi: Seoul National University College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.

Date: 2023
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DOI: 10.1038/s41467-023-37044-4

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