Scientists have identified a brain circuit that connects contextual memory with appetite, advancing understanding of binge eating and obesity while highlighting a promising new target for drug discovery.
Researchers at Mass General Brigham, Broad Institute of MIT and Harvard University have identified a set of brain cells that translate past experiences into appetite control, giving scientists new insight into how memory shapes eating behaviour. The findings suggest that dysfunction in this neural circuit could contribute to disordered eating and obesity, potentially leading to new treatment approaches. By pinpointing specific neurons and signalling pathways, the work also provides a more precise biological framework to guide future drug discovery efforts aimed at appetite regulation.
Linking memory and appetite
Our previous experiences influence not only how much we eat but also where and what we choose to consume. In preclinical models, the research team discovered a neural circuit that connects contextual memory with feeding behaviour.
Our previous experiences influence not only how much we eat but also where and what we choose to consume.
“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 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.”
The study focused on how the brain integrates memories of specific environments with signals that regulate hunger. Using mouse models, the researchers pinpointed a group of neurons known as prodynorphin-secreting neurons in the dorsolateral septum, referred to as DLS(Pdyn) neurons.
A relay between memory and feeding centres
The team found that DLS(Pdyn) neurons relay information between the hippocampus, which stores contextual memories, and the hypothalamus, which oversees feeding. This positioning allows the cells to act as a bridge between remembering a place and deciding whether to eat there.
Further experiments demonstrated that stimulating DLS(Pdyn) neurons suppressed feeding and promoted avoidance behaviours.
When the researchers silenced these neurons, or deleted the Pdyn gene within them, mice were no longer able to associate a favourable feeding experience with a particular location. In addition, the animals showed an increased appetite even in unfamiliar settings. These findings indicate that the circuit’s activity is shaped by experience, previously learned contexts and prodynorphin signalling.
Further experiments demonstrated that stimulating DLS(Pdyn) neurons suppressed feeding and promoted avoidance behaviours. This effect aligns with the known role of dynorphin, an endogenous opioid derived from prodynorphin, which mediates dysphoria or anti-reward signalling in the brain.
Implications for obesity treatments
The researchers also discovered that DLS(Pdyn) neurons express the receptor for GLP1, suggesting that GLP1-based drugs may exert some of their effects through this newly identified circuit, meaning it has relevance to both existing therapies and the development of next-generation compounds.
By clarifying how contextual memory influences appetite, the study provides a clearer picture of the biological mechanisms that can drive overeating.
“Dysfunction in dynorphin production or in the neural circuits that use it may contribute to disordered eating,” said first author Dr Travis Goode, a Research Fellow in the Sahay lab in the Department of Psychiatry at Mass General Brigham. “Our findings may point toward new brain targets for eating-related issues.”
By clarifying how contextual memory influences appetite, the study provides a clearer picture of the biological mechanisms that can drive overeating. The authors suggest that therapies aimed at restoring proper signalling within this circuit could help address conditions such as binge eating and obesity, particularly where eating behaviour becomes detached from environmental cues and past experience. More broadly, defining this pathway offers pharmaceutical researchers a tangible target for drug discovery programmes looking at more tailored and effective interventions for eating-related disorders.