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 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 microM). 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 ( approximately 30%) in the Ca2+-dependent K+-mediated afterhyperpolarization (AHP), because the K+ channel blocker apamin (1 microM) 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.
Norris
C M
CM
Department of Psychology and the Neurosciences Graduate Program, University of Virginia, Charlottesville, Virginia 22903, USA.
Halpain
S
S
Foster
T C
TC
D000375:Aging / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D001030:Apamin; D009543:Nifedipine