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

Authors: CASSIDY, RYAN - University Of Texas Health Science Center; LU, YUNGANG - University Of Texas Health Science Center; JERE, MADHAVI - Vassar College; TIAN, JIN-BIN - University Of Texas Health Science Center; XU, YUANZHONG - University Of Texas Health Science Center; MANGIERI, LEANDRA - University Of Texas Health Science Center; FELIX-OKOROJI, BLESSING - Rice University; SELEVER, JENNIFER - Baylor College Of Medicine; XU, YONG - Children'S Nutrition Research Center (CNRC); ARENKIEL, BENJAMIN - Baylor College Of Medicine; TONG, QINGCHUN - University Of Texas Health Science Center

Submitted to: Science Advances
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2019
Publication Date: 3/6/2019
Citation: Cassidy, R., Lu, Y., Jere, M., Tian, J., Xu, Y., Mangieri, L.R., Felix-Okoroji, B., Selever, J., Xu, Y., Arenkiel, B.R., Tong, Q. 2019. A lateral hypothalamus to basal forebrain neurocircuit promotes feeding by suppressing responses to anxiogenic environmental cues. Science Advances. 5(3):1640 https://doi.org/10.1126/sciadv.aav1640
DOI: https://doi.org/10.1126/sciadv.aav1640

Interpretive Summary: In animals, eating behavior is essential for survival but food seeking could be dangerous and thus there is a need to overcome anxiety associated with this danger. The brain mechanisms for the regulations of these behaviors remain unclear. Here we discovered a novel neural circuit within the brain that reduces anxiety and triggers eating behavior. This is important as it may provide a neurobiological basis for the link between eating and anxiety-related disorders.

Technical 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 (DBB^GABA) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LH^GABA). 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 LH^GABA -> DBB^GABA neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.