Enhanced postsynaptic inhibitory strength in hippocampal principal cells in high-performing aged rats.

Abstract

Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals). In hippocampal slices of these 3 aged groups (Y, AI, AU), we found that compared to the young, the miniature excitatory and inhibitory currents (mEPSCs and mIPSCs) were larger in amplitude in the granule cells of the AU group and smaller in the AI group. In contrast, in CA1 cells, neither the mEPSCs nor the mIPSCs were affected by age, whereas the extrasynaptic conductance responsible for tonic inhibition was selectively enhanced in CA1 cells of AU individuals. Tonic inhibition conductance was not affected by age in the granule cells. These results support the notion that upregulation of synaptic inhibition could be a necessary condition for the maintenance of performance during aging. These findings also underscore the notions that successful aging requires adaptive upregulation, not merely the preservation of youthful functionality, and that age effects are not homogeneous across hippocampal subfields.