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

Abstract

ABSTRACT 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.