Induction and experience-dependent consolidation of stable long-term potentiation lasting months in the hippocampus.
Long-term potentiation (LTP) is widely regarded as a memory mechanism, but it is not known whether it can last long enough to underlie very long-term memory. We report that high-frequency stimulation (HFS) paradigms applied to the rat dentate gyrus can elicit stable LTP lasting months and up to at least 1 year. The induction of stable LTP was sensitive to stimulation variables on the day of HFS and was associated with phosphorylation of cAMP response element-binding protein. The maintenance of stable LTP was also experience-dependent, because it was reversed when animals were exposed repeatedly to an enriched environment beginning 14 d post-HFS. However, stable LTP eventually consolidated over time and became resistant to reversal, because exposure to enriched environments 90 d post-HFS failed to influence stable LTP maintenance. Thus, LTP can be shown to meet one of the principal criteria for a very long-term memory storage mechanism. However, under naturalistic environmental conditions, LTP may normally be retained in the hippocampus for only short periods of time.
Abraham
Wickliffe C
WC
Department of Psychology, University of Otago, Dunedin, New Zealand. cabraham@psy.otago.ac.nz
Logan
Barbara
B
Greenwood
Jeffrey M
JM
Dragunow
Michael
M
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003720:Densitometry; D018891:Dentate Gyrus / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D004777:Environment; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D019580:Perforant Pathway / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D013995:Time
D017362:Cyclic AMP Response Element-Binding Protein; D016194:Receptors, N-Methyl-D-Aspartate