Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior

Leslie Jaesun Ha; Hyeon-Gu Yeo; Yu Gyeong Kim; Inhyeok Baek; Eunha Baeg; Young Hee Lee; Jinyoung Won; Yunkyo Jung; Junghyung Park; Chang‐Yeop Jeon; Keonwoo Kim; Jisun Min; Youngkyu Song; Jeong-Heon Park; Kyung Rok Nam; Sangkyu Son; Seng Bum Michael Yoo; Sung‐Hyun Park; Won Seok Choi; Kyung Seob Lim; Jae Yong Choi; Jee‐Hyun Cho; Youngjeon Lee; Hyung Jin Choi

doi:10.1101/2023.06.11.544288

NeurosciencebioRxivJun 11, 2023

Preprint

Hypothalamic neuronal activation in primates drives naturalistic goal-directed eating behavior

Leslie Jaesun Ha iD, Hyeon-Gu Yeo iD, Yu Gyeong Kim iD, Inhyeok Baek, Eunha Baeg iD, Young Hee Lee iD, Jinyoung Won iD, Yunkyo Jung, Junghyung Park iD, Chang‐Yeop Jeon iD, Keonwoo Kim iD, Jisun Min, Youngkyu Song, Jeong-Heon Park, Kyung Rok Nam iD, Sangkyu Son iD, Seng Bum Michael Yoo iD, Sung‐Hyun Park iD, Won Seok Choi iD, Kyung Seob Lim iD, Jae Yong Choi iD, Jee‐Hyun Cho iD, Youngjeon Lee iD, Hyung Jin Choi iD

Abstract

Eating addiction is the primary cause of modern obesity. Although the causal role of the lateral hypothalamic area (LHA) for eating is demonstrated in rodents, there is no evidence in primates regarding naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating by chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, which was specific for palatable food. PET and MRS validated the chemogenetic activation. Rs-fMRI result revealed that functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after the LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

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