Aging impairs the late phase of long-term potentiation at the medial perforant path-CA3 synapse in awake rats.

The effects of aging on long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 are well documented, but LTP at the medial perforant path (MPP)-CA3 synapse of aged animals has remained unexplored. Because the MPP-DG and Schaffer-collateral-CA1 synapses account for only about 20% of total hippocampal synapses, global understanding of how aging affects hippocampal plasticity has remained limited. Much is known about LTP induction in the hippocampal formation, whereas the mechanisms that regulate LTP maintenance are less understood, especially during aging. We investigated the effects of aging on MPP-CA3 LTP induction and maintenance in awake rats. As is the case in the DG and CA1, high-frequency stimulation-induced LTP at the MPP-CA3 synapse is normal in aged rats. These data indicate that N-methyl-D-aspartate (NMDA) receptor-mediated processes are intact at the MPP-CA3 synapse in aged rats. In contrast, aging impaired the magnitude and duration of MPP-CA3 LTP over a period of days. Also, these data are consistent with reports that area CA3 is especially susceptible to age-related changes. Our data suggest that aging impairs mechanisms that regulate the late phase of MPP-CA3 LTP and contribute to a more global understanding of how aging affects hippocampal plasticity. Copyright 2004 Wiley-Liss, Inc.