Age-Related Changes in Density, Arborization, and NMDA Receptor Expression in Somatostatin Interneurons of the Mouse mPFC

Aging is associated with progressive alterations in cortical circuits that compromise cognitive function. Somatostatin-positive (SST+) Martinotti interneurons, which regulate pyramidal cell activity in the medial prefrontal cortex (mPFC), are particularly relevant for inhibitory control, yet their age-related vulnerability remains poorly understood. Here, we examined GFP-labeled SST+ interneurons in mice at 3, 9, and 16 months of age, focusing on neuronal density, dendritic arborization, and expression of NMDA receptor subunits GluN1 and GluN2B. Our findings reveal a significant decline in SST+ interneuron density in aged male mice, whereas female mice displayed an increase in dendritic arborization with age. Analysis of NMDA receptor puncta showed a reduction in GluN1 and GluN2B density with increased puncta size in older animals. Together, these findings reveal age- and sex-dependent structural and molecular remodeling of SST+ interneurons in the mPFC.