Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, UTHealth McGovern Medical School, 7000 Fannin St., Houston, TX 77030, USA.
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.
Sci Adv. 2019 Mar 6;5(3):eaav1640. doi: 10.1126/sciadv.aav1640. eCollection 2019 Mar.
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) are responsive to indications of risk and receive monosynaptic inhibitory input from lateral hypothalamus GABAergic neurons (LH). Activation of this circuit reduces anxiety and causes indiscriminate feeding. We also found that diazepam rapidly reduces DBB activity while inducing indiscriminate feeding. Our study reveals that the LH→DBB neurocircuit overrides anxiogenic environmental cues to allow feeding and that this pathway may underlie the link between eating and anxiety-related disorders.
内部信号表明食物的吸引力，外部信号表明在特定环境中进食所涉及的风险。前者驱动的行为是饥饿的表现，后者则是焦虑的表现。在典型的抑郁症和厌食症等情况下，病理性焦虑与进食减少之间的联系是众所周知的。相反，苯二氮䓬类等抗焦虑药物会增加食欲。在这里，我们表明 Broca 斜角带（DBB）中的 GABA 能神经元对风险的指示有反应，并从外侧下丘脑 GABA 能神经元（LH）接收单突触抑制性输入。该回路的激活可降低焦虑并导致无差别进食。我们还发现，地西泮在诱导无差别进食的同时，可迅速降低 DBB 的活性。我们的研究揭示了 LH→DBB 神经回路可以忽略产生焦虑的环境线索，从而允许进食，并且该途径可能是进食与焦虑相关障碍之间的联系的基础。
