Cholinergic Basal Forebrain Connectivity to the Basolateral Amygdala Modulates Food Intake

Authors

Joshua Ortiz-Guzman
Jessica L Swanson
Evelyne K Tantry
Mikhail Kochukov
Kevin Ung
Angela P Addison
Snigdha Srivastava
Benjamin D Belfort
Emily Ji
Sean W Dooling
Sarah A Chen
Qingchun Tong
Benjamin R Arenkiel

Publication Date

3-1-2024

Journal

eNeuro

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.

Keywords

Mice, Animals, Basolateral Nuclear Complex, Basal Forebrain, Cholinergic Neurons, Cholinergic Agents, Eating, acetylcholine, basal forebrain, basolateral amygdala, circuits, feeding

Comments

PMID: 38383587