Brain Circuit Identified Linking Contextual Information with Appetite Control

Researchers from Mass General Brigham and the Broad Institute of MIT and Harvard have identified specific brain cells that connect contextual information with appetite control in preclinical models.

These findings suggest that issues within this brain circuit could contribute to disordered eating and obesity.
The identified neurons may represent a new target for treatment strategies.

Senior author Amar Sahay, PhD, of the Department of Psychiatry at Mass General Brigham, stated that

"the identified neural circuit is responsible for linking past experiences with current food preferences and aversions. This research could inform therapeutics for conditions like binge eating, which can stem from a loss of contextual eating control."

Understanding the Neural Mechanism

In mouse models, the researchers demonstrated that Prodynorphin-secreting neurons in the dorsolateral septum (DLS(Pdyn)) transmit information between the hippocampus (memory storage) and hypothalamus (feeding control).

Silencing these DLS(Pdyn) cells or deleting the Pdyn gene in them prevented mice from associating a positive feeding experience with a specific location. It also increased the mice's appetite even in unfamiliar locations, indicating that the circuit's activity is influenced by prior experiences, learned contexts, and prodynorphin signaling.

The study also found that stimulating DLS(Pdyn) neurons suppressed feeding and promoted avoidance behaviors. This aligns with the role of dynorphin, an endogenous opioid derived from prodynorphin, which mediates anti-reward signaling. The presence of GLP1 receptors on DLS(Pdyn) neurons suggests that widely used GLP1 drugs might operate partially through this circuit.

Implications for Treatment

First author Travis Goode, PhD, a Research Fellow in the Sahay lab, noted that

"dysfunction in dynorphin production or its associated neural circuits could contribute to eating disorders, potentially leading to new brain targets for these issues."

The results were published in Neuron.