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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #417495
Research Project: Molecular, Cellular, and Regulatory Aspects of Obesity Development

Location: Children's Nutrition Research Center

Title: Cholinergic basal forebrain connectivity to the basolateral amygdala modulates food intake

Author
item ORTIZ-GUZMAN, JOSHUA - Baylor College Of Medicine
item SWANSON, JESSICA - Baylor College Of Medicine
item TANTRY, EVELYNE - Baylor College Of Medicine
item KOCHUKOV, MIKHAIL - Baylor College Of Medicine
item UNG, KEVIN - Baylor College Of Medicine
item ADDISON, ANGELA - Baylor College Of Medicine
item SRIVASTAVA, SNIGDHA - Baylor College Of Medicine
item BELFORT, BENJAMIN - Baylor College Of Medicine
item JI, EMILY - Baylor College Of Medicine
item DOOLING, SEAN - Baylor College Of Medicine
item CHEN, SARAH - Baylor College Of Medicine
item TONG, QINGCHUN - University Of Texas Health Science Center
item ARENKIEL, BENJAMIN - Children'S Nutrition Research Center (CNRC)

Submitted to: eNeuro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2024
Publication Date: 3/5/2024
Citation: Ortiz-Guzman, J., Swanson, J.L., Tantry, E.K., Kochukov, M., Ung, K., Addison, A.P., Srivastava, S., Belfort, B.D., Ji, E., Dooling, S.W., Chen, S.A., Tong, Q., Arenkiel, B.R. 2024. Cholinergic basal forebrain connectivity to the basolateral amygdala modulates food intake. eNeuro. 11(3). Article ENEURO.0369-23.2024. https://doi.org/10.1523/ENEURO.0369-23.2024.
DOI: https://doi.org/10.1523/ENEURO.0369-23.2024

Interpretive Summary: The cholinergic basal forebrain has diverse targets thought to be involved with motivated behavior. Here we identified the basolateral amygdala, classically described for its role in anxiety and aggression, as a downstream target of the cholinergic basal forebrain circuits involved in feeding. These findings reveal a potential new therapeutic target for treating aspects of eating disorders.

Technical Abstract: Obesity results from excessive caloric input associated with overeating and presents a major public health challenge. The hypothalamus has received significant attention for its role in governing feeding behavior and body weight homeostasis. However, extrahypothalamic brain circuits also regulate appetite and consumption by altering sensory perception, motivation, and reward. We recently discovered a population of basal forebrain cholinergic (BFc) neurons that regulate appetite suppression. Through viral tracing methods in the mouse model, we found that BFc neurons densely innervate the basolateral amygdala (BLA), a limbic structure involved in motivated behaviors. Using channelrhodopsin-assisted circuit mapping, we identified cholinergic responses in BLA neurons following BFc circuit manipulations. Furthermore, in vivo acetylcholine sensor and genetically encoded calcium indicator imaging within the BLA (using GACh3 and GCaMP, respectively) revealed selective response patterns of activity during feeding. Finally, through optogenetic manipulations in vivo, we found that increased cholinergic signaling from the BFc to the BLA suppresses appetite and food intake. Together, these data support a model in which cholinergic signaling from the BFc to the BLA directly influences appetite and feeding behavior.