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Sci Adv. 2019 Mar 6;5(3):eaav1640. doi: 10.1126/sciadv.aav1640. eCollection 2019 Mar.

A lateral hypothalamus to basal forebrain neurocircuit promotes feeding by suppressing responses to anxiogenic environmental cues.

Author information

1
Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, UTHealth McGovern Medical School, 7000 Fannin St., Houston, TX 77030, USA.
2
MSTP, The University of Texas McGovern Medical School and MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 6767 Bertner Avenue S3.8344 Mitchell BSRB, Houston, TX 77030, USA.
3
Neuroscience Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, 6767 Bertner Avenue S3.8344 Mitchell BSRB, Houston, TX 77030, USA.
4
Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604, USA.
5
Department of Integrative Biology and Pharmacology, UTHealth McGovern Medical School, 6431 Fannin St., Houston, TX 77030-1892, USA.
6
Rice University, 6100 Main St., Houston, TX 77005-1892, USA.
7
Intellectual and Developmental Disabilities Research Center, Neuroconnectivity Core, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
8
Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, S640, Houston, TX 77030, USA.
9
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, 6621 Fannin St., Houston, TX 77030, USA.
10
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates St., Houston, TX 77030, USA.
11
Department of Neurobiology and Anatomy, UTHealth McGovern Medical School, 6431 Fannin St., Suite MSB 7.046 Houston, TX 77030, USA.

Abstract

Animals must consider competing information before deciding to eat: internal signals indicating the desirability of food and external signals indicating the risk involved in eating within a particular environment. The behaviors driven by the former are manifestations of hunger, and the latter, anxiety. The connection between pathologic anxiety and reduced eating in conditions like typical depression and anorexia is well known. Conversely, anti-anxiety drugs such as benzodiazepines increase appetite. Here, we show that GABAergic neurons in the diagonal band of Broca (DBBGABA) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LHGABA). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBBGABA activity while inducing indiscriminate feeding. Our study reveals that the LHGABA→DBBGABA neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.

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