An excitatory projection from the basal forebrain to the ventral tegmental area that underlies anorexia-like phenotypes.

Autor:	Cai J; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, Houston, TX 77030, USA., Jiang Y; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Xu Y; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Jiang Z; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Young C; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Li H; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Ortiz-Guzman J; Department of Molecular and Human Genetics and Department of Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA., Zhuo Y; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China., Li Y; State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China., Xu Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Arenkiel BR; Department of Molecular and Human Genetics and Department of Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: arenkiel@bcm.edu., Tong Q; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, Houston, TX 77030, USA; Department of Neurobiology and Anatomy of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: qingchun.tong@uth.tmc.edu.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Feb 07; Vol. 112 (3), pp. 458-472.e6. Date of Electronic Publication: 2023 Dec 05.
DOI:	10.1016/j.neuron.2023.11.001
Abstrakt:	Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia symptoms. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens. Collectively, our results point to overactivation of the glutamatergic BF → VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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