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The Journal of Neuroscience, November 15, 2002, 22(22):9932-9940
Theta-Frequency Synaptic Potentiation in CA1 In
Vitro Distinguishes Cognitively Impaired from Unimpaired Aged
Fischer 344 Rats
Geoffrey C.
Tombaugh,
Wayne B.
Rowe,
Ana R.
Chow,
Timothy H.
Michael, and
Gregory M.
Rose
Memory Pharmaceuticals Corporation, Montvale, New Jersey 07645
Hippocampal-dependent learning and memory deficits have been well
documented in aging rodents. The results of several recent studies have
suggested that these deficits arise from weakened synaptic plasticity
within the hippocampus. In the present study, we examined the
relationship between hippocampal long-term potentiation (LTP)
in vitro and spatial learning in aged (24-26
months) Fischer 344 rats. We found that LTP induced in the CA1
region using theta-frequency stimulation (5 Hz) is
selectively impaired in slices from a subpopulation of aged rats that
had shown poor spatial learning in the Morris water maze. LTP at
5 Hz in aged rats that did not show learning deficits was similar to
that seen in young (4-6 months) controls. We also found that 5 Hz LTP
amplitude strongly correlated with individual learning performance
among aged rats. The difference in 5 Hz LTP magnitude among aged rats
was not attributable to an altered response to 5 Hz stimulation
or to differences in the NMDA receptor-mediated field EPSP. In
addition, no performance-related differences in LTP were seen when LTP
was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz
LTP and spatial learning in learning-impaired rats were enhanced with
the selective muscarinic M2 antagonist
BIBN-99
(5,11-dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1-oxopentyl)ethylamino]propyl]-1-piperidinyl]acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.
Key words:
hippocampus; aging; spatial learning; LTP; memory; NMDA
receptor; muscarinic receptor
Copyright © 2002 Society for Neuroscience 0270-6474/02/22229932-09$05.00/0
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