Researchers from Mass General Brigham and the Broad Institute of MIT and Harvard have identified a brain circuit that translates past experiences into appetite control. This groundbreaking study, published in Neuron, reveals that dysfunction in this circuit could contribute to disordered eating and obesity, suggesting new potential targets for treatment.
According to the study, Prodynorphin-secreting neurons in the dorsolateral septum (DLS(Pdyn)) play a crucial role in relaying information between the hippocampus and hypothalamus. These brain regions are responsible for storing contextual memories and controlling feeding behaviors. The research indicates that these neurons help link past dining experiences with current food preferences and aversions.
Understanding the Brain’s Appetite Control Circuit
“We identified a neural circuit that is responsible for linking our prior experiences with current aversions and preferences when it comes to dining choices,” said Dr. Amar Sahay, the study’s senior author and a member of the Department of Psychiatry at Mass General Brigham. “These findings may shed light on therapeutics to treat disordered eating in humans such as binge eating that arises in part from loss of contextual control or calibration of eating.”
Using mouse models, the researchers demonstrated that silencing the DLS(Pdyn) neurons or deleting the Pdyn gene in these cells disrupted the mice’s ability to associate a previously favorable feeding experience with a specific location. This disruption led to increased appetite even in unfamiliar settings, highlighting the circuit’s role in appetite regulation based on past experiences.
Implications for Eating Disorders and Obesity
The study also found that stimulating DLS(Pdyn) neurons suppressed feeding and promoted avoidance, consistent with the role of dynorphin—an endogenous opioid made from prodynorphin that mediates dysphoria or anti-reward signaling. This discovery suggests that the DLS(Pdyn) neurons might be involved in the mechanisms of widely used GLP1 drugs, which are known for their appetite-suppressing effects.
“Dysfunction in dynorphin production or in the neural circuits that use it may contribute to disordered eating,” noted Dr. Travis Goode, the study’s first author and a Research Fellow in the Sahay lab. “Our findings may point toward new brain targets for eating-related issues.”
Research and Funding Details
The study’s authors include a team of researchers from Mass General Brigham and other institutions, such as Jason Bondoc Alipio, Cinzia Vicidomini, Devesh Pathak, Antoine Besnard, Michael D. Kritzer, Ain Chung, and Evan Macosko. Additional contributors include Mollie X. Bernstein, Michael S. Totty, Delara Chizari, Nina Sachdev, Xin Duan, Stephanie C. Hicks, and Larry S. Zweifel.
Funding for this research was provided by various grants and awards, including the Brain & Behavior Research Foundation Young Investigator Award, a Harvard Brain Initiative Travel Grant, and several NIH grants. These contributions highlight the collaborative effort and extensive support behind this significant scientific advancement.
Future Directions and Potential Treatments
The discovery of this brain circuit opens new avenues for understanding and treating eating disorders and obesity. By targeting the DLS(Pdyn) neurons and their pathways, researchers hope to develop more effective therapies that address the underlying neural mechanisms of disordered eating.
As the study progresses, further research will be needed to explore how these findings can be translated into clinical applications for humans. The potential to develop targeted treatments based on individual neural circuitry is a promising step forward in addressing the complex issue of appetite control and eating disorders.
The implications of this research extend beyond the realm of neuroscience, offering hope for millions of individuals struggling with eating-related issues worldwide. As scientists continue to unravel the mysteries of the brain, discoveries like these bring us closer to a deeper understanding of human behavior and health.
