Using a binge-eating-induced compulsive eating (BiCOM) mouse paradigm, this study examined how medial prefrontal cortex (mPFC) inputs to rostral zona incerta GABAergic neurons (rZI⁺ᴳᴬᴮᴬ) drive compulsive eating, and whether mPFC–rZI functional connectivity is relevant in humans with binge eating and obesity.
Bidirectional manipulation of rZI⁺ᴳᴬᴮᴬ neurons or their mPFC inputs causally modulated compulsive eating in mice; in vivo imaging revealed BiCOM reshaped mPFC dynamics into persistent attractor states selective for palatable food; human fMRI showed mPFC–rZI connectivity correlated with both body weight and binge-eating severity.
Full text was not available — sample sizes, effect sizes, and methodological details (e.g., human fMRI cohort demographics, statistical thresholds) could not be verified. Mouse-to-human translation of circuit-level findings remains speculative. The BiCOM paradigm's fidelity as a model of clinical BED has not been independently validated.
The mPFC–rostral zona incerta circuit is a candidate therapeutic target for binge-eating disorder and obesity, but clinical application requires further human validation. Clinicians should watch for translational studies testing neuromodulation of this pathway.
