TY - JOUR T1 - Reversal of Age-Related Alterations in Synaptic Plasticity by Blockade of L-Type Ca<sup>2+</sup> Channels JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3171 LP - 3179 DO - 10.1523/JNEUROSCI.18-09-03171.1998 VL - 18 IS - 9 AU - Christopher M. Norris AU - Shelley Halpain AU - Thomas C. Foster Y1 - 1998/05/01 UR - http://www.jneurosci.org/content/18/9/3171.abstract N2 - The role of L-type Ca2+ channels in the induction of synaptic plasticity in hippocampal slices of aged (22–24 months) and young adult (4–6 months) male Fischer 344 rats was investigated. Prolonged 1 Hz stimulation (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 nifedipine (10 μm). When 5 Hz stimulation (900 pulses) was used to modify synaptic strength, nifedipine facilitated synaptic enhancement in slices from aged, but not young, adult rats. This enhancement was pathway-specific, reversible, and impaired by the NMDA receptor (NMDAR) antagonist dl-2-amino-5-phosphonopentanoic acid (AP5). Induction of long-term potentiation (LTP) in aged rats, using 100 Hz stimulation, occluded subsequent synaptic enhancement by 5 Hz stimulation, suggesting that nifedipine-facilitated enhancement shares mechanisms in common with conventional LTP. Facilitation of synaptic enhancement by nifedipine likely was attributable to a reduction (∼30%) in the Ca2+-dependent K+-mediated afterhyperpolarization (AHP), because the K+ channel blocker apamin (1 μm) similarly reduced the AHP and promoted synaptic enhancement by 5 Hz stimulation. In contrast, apamin did not block LTD induction using 1 Hz stimulation, suggesting that, in aged rats, the AHP does not influence LTD and LTP induction in a similar way. The results indicate that, during aging, L-channels can (1) facilitate LTD 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. ER -