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The Journal of Neurophysiology Vol. 86 No. 3 September 2001, pp. 1289-1296
Copyright ©2001 by the American Physiological Society
Department of Neurobiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272-0095
Morgan, S. L. and
T. J. Teyler.
Electrical Stimuli Patterned After the Theta-Rhythm Induce
Multiple Forms of LTP. J. Neurophysiol. 86: 1289-1296, 2001. The induction of long-term potentiation (LTP) by
high-frequency stimulation is considered an acceptable model for the
study of learning and memory. In area CA1 calcium influx through
N-methyl-D-aspartate receptors (NMDARs; nmdaLTP)
and/or L-type voltage-dependent calcium channels (vdccLTP) results in
distinct forms of LTP. In the light of significant accumulation of
knowledge about patterns of naturally occurring activity in the intact
animal, we examined whether the application of stimuli patterned after
natural activity induced nmdaLTP and/or vdccLTP. In rat hippocampal
slices we examined LTP induced by three types of patterned stimulation
short (S-TBS), long (L-TBS), and high-intensity long theta-patterned
stimulation (HL-TBS). The patterns of stimulation were applied in
control, nifedipine (blocks vdccLTP),
D,L-2-amino-5-phosphonovaleric acid (APV; blocks nmdaLTP),
or APV and nifedipine containing media. We found that S-TBS resulted in
LTP that was completely attenuated in the presence of APV but was
unaffected by nifedipine. Thus S-TBS results in the selective induction
of nmdaLTP. L-TBS resulted in LTP that was completely blocked by APV
and only partially blocked by nifedipine. Therefore L-TBS results in a
compoundLTP consisting of both nmdaLTP and vdccLTP components. In the
presence of APV, HL-TBS resulted in vdccLTP, and when APV and
nifedipine were both present, LTP was completely blocked. Thus HL-TBS
results in a vdccLTP in isolation when APV is present. We also examined
saturation of S-TBS-induced LTP (nmdaLTP) by applying S-TBS at short
intervals. When nifedipine was present, multiple S-TBS trains resulted
in a substantially smaller final LTP as compared with controls. We conclude that multiple bursts of S-TBS eventually summate to result in
compoundLTP. Stimuli patterned after innate rhythms in the hippocampus
effectively induce nmdaLTP (S-TBS), compoundLTP (L-TBS), or vdccLTP
(HL-TBS).
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