Brain Circuit Linking Memory and Appetite Identified, Offering Modern Hope for Obesity Treatment
Scientists have pinpointed a brain circuit that connects contextual memory with appetite, potentially revolutionizing our understanding of binge eating and obesity. The discovery highlights a promising new target for drug development, offering hope for more effective treatments for disordered eating.
How Memory Shapes Eating Behavior
Researchers at Mass General Brigham and the Broad Institute of MIT and Harvard University have identified a specific set of brain cells that translate past experiences into appetite control. This research provides new insight into how memory influences our eating habits – not just 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,” explained Dr. Amar Sahay, PhD, of the Department of Psychiatry at Mass General Brigham, who is also a Broad associate member. “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 Role of DLS(Pdyn) Neurons
The study, published in Neuron, focused on how the brain integrates memories of specific environments with signals that regulate hunger. Using preclinical models, the researchers identified prodynorphin-secreting neurons in the dorsolateral septum, referred to as DLS(Pdyn) neurons. These neurons act as a crucial relay point between the hippocampus – the brain region responsible for storing contextual memories – and the hypothalamus, which controls feeding behavior.
Experiments revealed that stimulating DLS(Pdyn) neurons suppressed feeding and triggered avoidance behaviors. Conversely, silencing these neurons or deleting the Pdyn gene within them disrupted the ability of mice to associate a positive feeding experience with a particular location. The animals also exhibited increased appetite even in unfamiliar environments. These findings demonstrate that the circuit’s activity is shaped by experience, learned contexts, and prodynorphin signaling.
Dynorphin and GLP1: Implications for Treatment
Further investigation showed that DLS(Pdyn) neurons express the receptor for GLP1, a key target for existing obesity and diabetes medications. This suggests that GLP1-based drugs may exert some of their effects by modulating this newly identified brain circuit.
“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.”
Obesity and Machine Learning Research
The Broad Institute is also actively involved in leveraging machine learning to tackle metabolic diseases like obesity. A recent machine learning challenge, the Obesity Machine Learning Challenge: Tackling Metabolic Diseases, aims to predict how gene perturbations influence the behavior of adipocytes – the cells responsible for storing fat. Top predictions from this challenge will be experimentally validated in Broad Institute labs.
Looking Ahead
By clarifying the biological mechanisms that drive overeating, this research provides a clearer path toward developing more targeted and effective therapies for conditions like binge eating and obesity. The identification of the DLS(Pdyn) circuit offers a tangible target for drug discovery programs focused on restoring proper signaling within this critical brain pathway.