Abstract

Obesity is among the most pressing public-health challenges, driven largely by overconsumption of palatable, energy-dense foods in modern food environments. Current weight-loss drugs act primarily by engaging homeostatic satiety pathways rather than disengaging hedonic feeding pathways—the reinforcing drive to consume palatable food for reward rather than caloric need. Yet hedonic drive is a cardinal contributor to diet-induced obesity, motivating overconsumption that serves reward rather than physiological need. Combating obesity therefore requires identifying the neural substrates whose manipulation can reduce this drive. This dissertation identifies GABAergic neurons of the ventral pallidum (VPGABA neurons) as a forebrain population that drives hedonic feeding and is required for diet-induced obesity in rodents. VPGABA neurons selectively promote high-fat intake in sated animals, operate independently of hunger signaling, and exhibit endogenous dynamics that track the duration of consumption. VPGABA ablation confers obesity resistance while sparing homeostatic feeding, implicating these neurons and their downstream projections as candidates for interventions that curb overconsumption rather than broadly suppressing satiety, to induce long-lasting weight loss.

Committee Chair

Alexxai Kravitz

Committee Members

Daniel Castro; Marco Pignatelli; Tamara Hershey; Zachary Knight

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

8-13-2026

Language

English (en)

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Available for download on Thursday, August 12, 2027

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Neurosciences Commons

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