A cortical-hypothalamic neural circuit for compulsive eating in mice

Area of Science:

• Neuroscience
• Eating Disorders Research
• Obesity Research

Background:

• Binge-eating disorder (BED) is a prevalent eating disorder linked to obesity.
• The medial prefrontal cortex (mPFC) is involved in compulsive behaviors and feeding regulation.
• The precise neural pathways connecting the mPFC to hypothalamic feeding circuits remain unclear.

Purpose of the Study:

• To investigate the role of mPFC-hypothalamic interactions in compulsive eating.
• To identify specific neural populations driving binge-eating behaviors.
• To explore potential therapeutic targets for BED and obesity.

Main Methods:

• Development of a binge-eating-induced compulsive eating (BiCOM) mouse model.
• Optogenetic manipulation of rostral zona incerta GABAergic (rZI GABA) neurons and their mPFC inputs.
• In vivo neural activity imaging in mice during BiCOM.
• Human functional magnetic resonance imaging (fMRI) to assess mPFC-rZI connectivity.

Main Results:

• rZI GABA neurons were identified as key drivers of compulsive eating in the BiCOM model.
• Modulation of rZI GABA neurons or their mPFC connections altered compulsive eating.
• BiCOM induced persistent neural activity patterns in the mPFC selective for palatable food.
• Human mPFC-rZI connectivity correlated with body weight and binge eating severity.

Conclusions:

• A novel cortical-hypothalamic circuit involving mPFC and rZI GABA neurons mediates compulsive eating.
• This circuit represents a potential therapeutic target for binge-eating disorder and obesity.
• Findings provide mechanistic insights into the neural basis of maladaptive feeding behaviors.