Aging Differentially Alters Forms of Long-term Potentiation in Rat
Hippocampal Area CA1.
Subbakrishna Shankar, Timothy J. Teyler, and Norman Robbins.
Department of Neuroscience, Case Western Reserve University School of
Medicine, Cleveland, Ohio 44106; Neurobiology Department, NE Ohio
Universities College of Medicine, Rootstown, Ohio 44272.
APStracts 4:0248N, 1997.
ABSTRACT
Long term potentiation (LTP) of the Schaffer collateral/commissural inputs to
CA1 in the hippocampus has been shown to consist of N-methyl-d-aspartate
receptor (NMDAR) and voltage dependent calcium channel (VDCC) dependent forms.
In this study, the relative contributions of these two formsof LTP in in vitro
hippocampal slices from young (2 month) and old (24 month) Fischer 344 rats
were examined. Excitatory post-synaptic potentials were recorded
extracellularly from stratum radiatum before and after a tetanic stimulus
consisting of four 200 Hz, 0.5 sec trains given 5 sec apart. Under control
conditions, a compound LTP consisting of both forms was induced and was
similar, in both time course and magnitude, in young and old animals. NMDAR
dependent LTP (nmdaLTP), isolated by the application of 10 æM nifedipine (a
voltage-dependent calcium channel blocker), was significantly reduced in
magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the
application of 50 æM APV, was significantly larger in aged animals. While in
young animals both LTP forms reached stable values 40-60 min post-tetanus, in
aged animals vdccLTP increased and nmdaLTP decreased during this time. In both
young and old animals, the sum of the two isolated LTP forms approximated the
magnitude of the compound LTP, and application of APV and nifedipine or
genestein (a tyrosine kinase inhibitor) together blocked potentiation. These
results suggest that aging causes a shift in synaptic plasticity from NMDAR
dependent mechanisms to VDCC dependent mechanisms. The data are consistent
with previous findings of increased L-type calcium current and decreased NMDAR
number in aged CA1 cells, and may help explain age-related deficits in
learning and memory.
Received 21 July 1997; accepted in final form 9 September 1997.
APS Manuscript Number J600-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997