Location: Children's Nutrition Research Center
Title: Activation of basal forebrain-to-lateral habenula circuitry drives reflexive aversion and suppresses feeding behaviorAuthor
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SWANSON, JESSICA - Baylor College Of Medicine |
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ORTIZ-GUZMAN, JOSHUA - Baylor College Of Medicine |
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SRIVASTAVA, SNIGDHA - Baylor College Of Medicine |
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CHIN, PEY-SHYUAN - Baylor College Of Medicine |
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DOOLING, SEAN - Baylor College Of Medicine |
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HANSON MOSS, ELIZABETH - Baylor College Of Medicine |
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KOCHUKOV, MIKHAIL - Baylor College Of Medicine |
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HUNT, PATRICK - Baylor College Of Medicine |
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PATEL, JAY - Texas Children'S Hospital |
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PEKAREK, BRANDON - Baylor College Of Medicine |
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TONG, QINGCHUN - University Of Texas Health Science Center |
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ARENKIEL, BENJAMIN - Children'S Nutrition Research Center (CNRC) |
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 12/13/2022 Publication Date: 12/21/2022 Citation: Swanson, J.L., Ortiz-Guzman, J., Srivastava, S., Chin, P., Dooling, S.W., Hanson Moss, E., Kochukov, M., Hunt, P.J., Patel, J.M., Pekarek, B.T., Tong, Q., Arenkiel, B.R. 2022. Activation of basal forebrain-to-lateral habenula circuitry drives reflexive aversion and suppresses feeding behavior. Scientific Reports. 12. Article 22044. https://doi.org/10.1038/s41598-022-26306-8. DOI: https://doi.org/10.1038/s41598-022-26306-8 Interpretive Summary: We have previously found that glutamatergic neurons in the cholinergic basal forebrain regulate aversion behaviors associated with food avoidance. Here we show that such aversion mediated via this circuitry, manifests through signaling to the lateral habenula. Moreover, we showed that this aversion response is reflex-like, in that it does not require top-down cortical or hippocampal input. Together these findings reveal the lateral habenula as a putative target to treat anxiety and/or eating disorders. Technical Abstract: Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related odors. Optogenetic activation of BF-to-LHb circuitry drives robust, reflexive-like aversion. Furthermore, activation of this circuitry suppresses the drive to eat in a fasted state. Together, these data reveal a role of basal forebrain glutamatergic neurons in modulating LHb-associated aversion and feeding behaviors by sensing environmental cues. |