An Excitatory Projection from the Basal Forebrain to the Ventral Tegmental Area That Underlies Anorexia-Like Phenotypes

Authors

Jing Cai
Yanyan Jiang
Yuanzhong Xu
Zhiying Jiang
Claire Young
Hongli Li
Joshua Ortiz-Guzman
Yizhou Zhuo
Yulong Li
Yong Xu
Benjamin R Arenkiel
Qingchun Tong

Language

English

Publication Date

2-7-2024

Journal

Neuron

DOI

10.1016/j.neuron.2023.11.001

PMID

38056455

PMCID

PMC10922337

PubMedCentral® Posted Date

2-7-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia symptoms. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens. Collectively, our results point to overactivation of the glutamatergic BF → VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release.

Keywords

Mice, Animals, Ventral Tegmental Area, Dopamine, Basal Forebrain, Anorexia, Phenotype, Dopaminergic Neurons, Basal forebrain, VTA, glutamatergic neurons, feeding, stress, anorexia, dopamine

Published Open-Access

yes

Recommended Citation

Cai, Jing; Jiang, Yanyan; Xu, Yuanzhong; et al., "An Excitatory Projection from the Basal Forebrain to the Ventral Tegmental Area That Underlies Anorexia-Like Phenotypes" (2024). Faculty and Staff Publications. 3470.
https://digitalcommons.library.tmc.edu/baylor_docs/3470