Overview
- Mass General Brigham and Broad Institute researchers identified Pdyn-expressing somatostatin neurons in the dorsolateral septum that receive dorsal hippocampal input and project to lateral hypothalamic feeding modules.
- Silencing these cells or deleting the Pdyn gene prevented mice from linking prior positive feeding experiences to place and increased eating in unfamiliar settings.
- Optogenetic stimulation of the identified neurons suppressed food intake and promoted avoidance, aligning with dynorphin’s anti-reward signaling role.
- Single-cell transcriptomics, transsynaptic tracing, electrophysiology, and in vivo calcium imaging established the circuit’s connectivity and context-dependent activity.
- The neurons express GLP-1 receptors, raising a testable hypothesis about how GLP-1 drugs may act in the brain, with all findings reported in Neuron on February 12, 2026 and not yet validated in humans.