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The Journal of Neuroscience, May 1, 1998, 18(9):3171-3179
Reversal of Age-Related Alterations in Synaptic Plasticity by
Blockade of L-Type Ca2+ Channels
Christopher M.
Norris1,
Shelley
Halpain2, and
Thomas C.
Foster1
1 Department of Psychology and the Neurosciences
Graduate Program, University of Virginia, Charlottesville, Virginia
22903, and 2 Department of Cell Biology, The Scripps
Research Institute, La Jolla, California 92037
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.
Key words:
Key Words: long-term depression; long-term potentiation; afterhyperpolarization; aging; hippocampus; Fischer 344
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893171-09$05.00/0
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