November 3, 2022

Social behavior brain circuitry

Vanderbilt researchers have identified a novel mechanism regulating social behavior: Neuropeptide Y signaling in the nucleus accumbens brain region.

by Leigh MacMillan

Social interaction is an integral human behavior that is disrupted in many psychiatric disorders. 

Neuropeptide Y (NPY), an abundant brain peptide that acts through multiple receptors to modulate neuronal signaling, encourages prosocial behavior across the animal kingdom. Whether NPY modulates signaling in the nucleus accumbens, a brain region involved in social behavior, is unknown. 

Brad Grueter, PhD, and colleagues have now used patch-clamp electrophysiology of nucleus accumbens neurons to demonstrate that NPY Y1r and Y5r receptors enhance, and Y2r receptors depress, excitatory synaptic transmission in a cell-type specific manner. They showed that inhibition of an enzyme that breaks down NPY shifted the effect of NPY to a Y1r-dominated effect. Direct infusion of NPY or a Y1r agonist into the nucleus accumbens increased social interaction in an animal model. 

The findings, reported in Neuropharmacology, identify NPY signaling in the nucleus accumbens as a novel mechanism regulating social behavior and suggest a strategy for shifting this signaling for therapeutic purposes.

Co-authors include Nicholas Smith, Veronika Kondev and Thomas Hunt. This research was supported by the Department of Anesthesiology at Vanderbilt University Medical Center.