Ever wondered why you crave certain foods in specific places or situations? It turns out, your brain has a secret playbook for deciding when and what to eat, and it’s all tied to your past experiences. Researchers from Mass General Brigham and the Broad Institute of MIT and Harvard have uncovered a fascinating brain circuit that acts like a culinary GPS, linking memories of past meals to your current appetite. But here’s where it gets controversial: could this discovery hold the key to understanding—and treating—disordered eating and obesity? Let’s dive in.
In a groundbreaking study published in Neuron (https://www.cell.com/neuron/fulltext/S0896-6273(26)00050-4), scientists used preclinical models to identify a specific group of brain cells that act as the middleman between your memories and your appetite. These cells, located in the dorsolateral septum (DLS), secrete a protein called prodynorphin (Pdyn) and play a crucial role in deciding whether you’ll indulge in a snack or pass it up based on past experiences. For instance, if you’ve had a satisfying meal in a particular café, these neurons help you associate that positive experience with the location, influencing future dining choices.
And this is the part most people miss: when these neurons malfunction, it could lead to a loss of control over eating habits, potentially contributing to conditions like binge eating. Senior author Amar Sahay, PhD, explains, ‘We’ve identified a neural circuit that bridges our past experiences with our current food preferences. This could open doors to new therapies for disordered eating, especially when contextual control over eating is lost.’
Using mouse models, the team discovered that DLS(Pdyn) neurons act as a relay system between the hippocampus (where memories are stored) and the hypothalamus (which controls feeding). When these neurons were silenced or the Pdyn gene was deleted, mice lost their ability to associate a positive feeding experience with a location and ate more, even in unfamiliar settings. This suggests that the circuit’s activity is heavily influenced by past experiences and prodynorphin signaling.
Here’s another intriguing twist: stimulating these neurons suppressed feeding and promoted avoidance, a behavior linked to dynorphin, a chemical derived from prodynorphin that triggers feelings of dysphoria or anti-reward. Interestingly, DLS(Pdyn) neurons also express receptors for GLP1, a hormone targeted by popular weight-loss drugs. This raises the question: Could GLP1 medications be working, in part, by modulating this very circuit?
First author Travis Goode, PhD, adds, ‘Dysfunction in dynorphin production or the circuits that use it might contribute to disordered eating. Our findings could point to new brain targets for addressing eating-related issues.’
But here’s the controversial part: If this circuit is so central to appetite control, should we be focusing more on neurobiological interventions rather than just dietary changes? Could manipulating these neurons offer a more effective solution for obesity and eating disorders? We’d love to hear your thoughts in the comments.
The study, titled ‘A dorsal hippocampus-prodynorphinergic dorsolateral septum-to-lateral hypothalamus circuit mediates contextual gating of feeding,’ (DOI: 10.1016/j.neuron.2026.01.025) involved a multidisciplinary team of researchers, including Jason Bondoc Alipio, Cinzia Vicidomini, and Evan Macosko, among others. Funding was provided by various institutions, including the NIH, Harvard Brain Initiative, and the Simons Collaboration on Plasticity and the Aging Brain.
This research not only sheds light on the intricate relationship between memory and appetite but also sparks a broader conversation about the future of treating eating disorders. What do you think? Is this the breakthrough we’ve been waiting for, or are we overlooking simpler solutions? Let us know below!
