ROLE OF TEMPORAL SUMMATION IN AGE-RELATED LONG-TERM POTENTIATION-INDUCTION DEFICITS

Hippocampal long-term potentiation (LTP) is reduced in aged relative t o young F-344 rats when peri-threshold stimulation protocols (several stimulus pulses at 100-200 Hz) are used. The present study was designe d to examine the possibility that this LTP-induction deficit is caused by a reduced overlap of Schaffer-collateral inputs onto CA1 pyramidal cells (input cooperativity). This reduced input cooperativity would d ecrease the levels of postsynaptic depolarization during LTP induction , which might account for the age-related LTP deficit. Both behavioral data (Morris Water Maze) and electrophysiological data (intracellular recordings from hippocampal slices) were collected from adult and age d F-344 rats. To counter the effects of reduced input cooperativity, s timulus intensities were adjusted to elicit baseline excitatory postsy naptic potentials (EPSPs) of equivalent amplitude in aged and young ra ts. Contrary to expectations, however, an age-related LTP-induction de ficit was still observed. Further evaluation of the electrophysiologic al data revealed that temporal summation of multiple EPSPs during high -frequency stimulation was impaired in the aged rats. Thus, despite th e equalization across age groups of the baseline EPSP amplitudes, the cells of aged rats were less depolarized during the LTP-inducing stimu lation than were those of young rats. This reduced total depolarizatio n was not an artifact of the higher stimulus intensity used on aged an imals, nor was it caused by a failure of aged rats' CA1 afferents to f ollow high-frequency stimulation. The present data therefore suggest t hat there is a deficit in the ability of aged rats' synapses to provid e the sustained depolarization necessary to activate the LTP-induction cascade. (C) 1997 Wiley-Liss, Inc.