REVERSAL OF AGE-RELATED ALTERATIONS IN SYNAPTIC PLASTICITY BY BLOCKADE OF L-TYPE CA2+ CHANNELS

The role of L-type Ca2+ channels in the induction of synaptic plastici ty in hippocampal slices of aged (22-24 months) and young adult (4-6 m onths) male Fischer 344 rats was investigated. Prolonged 1 Hz stimulat ion (900 pulses) of Schaffer collaterals, which normally depresses CA3 /CA1 synaptic strength in aged rat slices, failed to induce long-term depression (LTD) during bath application of the L-channel antagonist n ifedipine (10 mu M). When 5 Hz stimulation (900 pulses) was used to mo dify synaptic strength, nifedipine facilitated synaptic enhancement in slices from aged, but not young, adult rats. This enhancement was pat hway-specific, reversible, and impaired by-the NMDA receptor (NMDAR) a ntagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Induction of lon g-term potentiation (LTP) in aged rats, using 100 Hz stimulation, occl uded subsequent synaptic enhancement by 5 Hz stimulation, suggesting t hat nifedipine-facilitated enhancement shares mechanisms in common wit h conventional LTP Facilitation of synaptic enhancement by nifedipine likely was attributable to a reduction (similar to 30%) in the Ca2+-de pendent K+-mediated afterhyperpolarization (AHP), because the K+ chann el blocker apamin (1 mu M) similarly reduced the AHP and promoted syna ptic enhancement by 5 Hz stimulation. In contrast, apamin did not bloc k LTD induction using 1 Hz stimulation, suggesting that, in aged rats, the AHP does not influence LTD and LTP induction in a similar way. Th e results indicate that, during aging, L-channels can (1) facilitate L TD induction during low rates of synaptic activity and (2) impair LTP induction during higher levels of synaptic activation via an increase in the Ca2+-dependent AHP.