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Journal of Neuroscience, Vol 14, 5793-5806, Copyright © 1994 by Society for Neuroscience
LTP saturation and spatial learning disruption: effects of task variables and saturation levels
CA Barnes, MW Jung, BL McNaughton, DL Korol, K Andreasson and PF Worley
Department of Psychology, University of Arizona, Tucson 85724.
The prediction that "saturation" of LTP/LTE at hippocampal synapses should
impair spatial learning was reinvestigated in the light of a more specific
consideration of the theory of Hebbian associative networks, which predicts
a nonlinear relationship between LTP "saturation" and memory impairment.
This nonlinearity may explain the variable results of studies that have
addressed the effects of LTP "saturation" on behavior. The extent of LTP
"saturation" in fascia dentata produced by the standard chronic LTP
stimulation protocol was assessed both electrophysiologically and through
the use of an anatomical marker (activation of the immediate-early gene
zif268). Both methods point to the conclusion that the standard protocols
used to induce LTP do not "saturate" the process at any dorsoventral level,
and leave the ventral half of the hippocampus virtually unaffected. LTP-
inducing, bilateral perforant path stimulation led to a significant deficit
in the reversal of a well-learned spatial response on the Barnes circular
platform task as reported previously, yet in the same animals produced no
deficit in learning the Morris water task (for which previous results have
been conflicting). The behavioral deficit was not a consequence of any
after-discharge in the hippocampal EEG. In contrast, administration of
maximal electroconvulsive shock led to robust zif268 activation throughout
the hippocampus, enhancement of synaptic responses, occlusion of LTP
produced by discrete high- frequency stimulation, and spatial learning
deficits in the water task. These data provide further support for the
involvement of LTP-like synaptic enhancement in spatial learning.
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