LTP induction threshold change in old rats at the perforant path–granule cell synapse

Old, memory-deficient rats do not show a change in the threshold for long-term potentiation (LTP) induction in hippocampal region CA1. This observation suggests that defective NMDA receptor mechanisms at the Schaffer collateral—CA1 pyramidal cell synapse cannot explain age-related LTP induction deficits that are observed under some stimulation protocols. The effects of aging on functional electrophysiology are not, however, identical between hippocampal subregions. In fact, at the perforant path—granule cell synapse of rats NMDA receptor-mediated responses are reduced, suggesting a possible change in the threshold for LTP induction at this synapse. This hypothesis was tested in the present experiment. We found that when weak orthodromic stimulation of medial perforant path fibers is paired with intracellular current injection of granule cells, the threshold for LTP induction is elevated in aged, spatial memory-impaired rats compared to middle-aged and young controls. Thus, in addition to there being fewer total medial perforant path synaptic contacts in old rats, greater depolarization and input convergence is required before durable modification of synaptic strength can be induced.