Age-related electrophysiological changes in layer 5 pyramidal cells and interneurons of the rat medial prefrontal cortex.

Abstract

The functional integrity of the medial prefrontal cortex (mPFC) depends on the accurate integration of synaptic inputs via the dynamic interplay between pyramidal cells (PCs) and GABAergic interneurons. In this comparative study, we report how aging alters the electrophysiological profiles of layer 5 PCs and local interneurons in the rat mPFC. Relative to 2-month-old rats, 24 ± 2-month-old acute brain slices containing the prelimbic area of mPFC exhibited changes in the passive and active membrane properties governing neuronal excitability. Whole-cell patch-clamp recordings showed reduced firing frequency in PCs and increased firing frequency in interneurons. Analysis of ionic conductances revealed decreased voltage-gated sodium current amplitude in PCs, whereas interneurons exhibited decreased potassium current amplitudes. Extracellular recordings further identified network-level impairments with aging, including reduced population spike amplitude and diminished gain, indicating decreased synaptic recruitment. Short-term plasticity was selectively affected: at 10 and 30Hz, aging increased the decay time constant and attenuated synaptic depression by preserving higher response amplitudes, while responses to 50Hz stimulation remained unchanged. By recording both neuronal types within the same experimental and anatomical framework, this study enabled a unified interpretation of how cell-type-specific aging adaptations emerge within a shared microenvironment. Overall, aging differentially disrupts excitability and ionic mechanisms in pyramidal and interneuron populations, leading to impaired synaptic integration and altered short-term plasticity in mPFC microcircuits. Collectively, these findings suggest that disrupted synaptic integration and intrinsic neuronal function in the aged neocortex may contribute to age-related cognitive decline.