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The Journal of Neuroscience, November 1, 2002, 22(21):9626-9634

Induction and Experience-Dependent Consolidation of Stable Long-Term Potentiation Lasting Months in the Hippocampus

Wickliffe C. Abraham¹, Barbara Logan¹, Jeffrey M. Greenwood², and Michael Dragunow²

¹ Department of Psychology, University of Otago, Dunedin, New Zealand, and ² Department of Pharmacology, University of Auckland Medical School, Auckland, New Zealand

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.

Key words: long-term potentiation; memory; hippocampus; enriched environment; CREB; depotentiation; NMDA receptor

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22219626-09$05.00/0

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