How long will long-term potentiation last?

Abstract

The paramount feature of long-term potentiation (LTP) as a memory mechanism is its characteristic persistence over time. Although the basic phenomenology of LTP persistence was established 30 years ago, new insights have emerged recently about the extent of LTP persistence and its regulation by activity and experience. Thus, it is now evident that LTP, at least in the dentate gyrus, can either be decremental, lasting from hours to weeks, or stable, lasting months or longer. Although mechanisms engaged during the induction of LTP regulate its subsequent persistence, the maintenance of LTP is also governed by activity patterns post-induction, whether induced experimentally or generated by experience. These new findings establish dentate gyrus LTP as a useful model system for studying the mechanisms governing the induction, maintenance and interference with long-term memory, including very long-term memory lasting months or longer. The challenge is to study LTP persistence in other brain areas, and to relate, if possible, the properties and regulation of LTP maintenance to these same properties of the information that is actually stored in those regions.Keywords: long-term potentiation; hippocampus; maintenance mechanisms; enriched environment; neurogenesis; metaplasticitySince the pioneering studies performed 30 years ago by Tim Bliss, Terje Lømo and Tony Gardner-Medwin (Bliss & Lømo 1973;Bliss & Gardner-Medwin 1973), LTP has generated enormous interest as a potential memory mechanism. This is because LTP exhibits numerous properties expected of an associative memory mechanism, such as rapid induction, input specificity, associative interactions, persistence, and dependence on correlated preand postsynaptic activity. The close similarity between these features and those of the learning rule of Hebb (1949) has added lustre to the LTP phenomenon. In addition, there is important yet complex regulation of LTP by prior synaptic activity (metaplasticity), neighbouring afferents (e.g. synaptic tagging), and state variables such as levels of stress hormones and activity in neuromodulatory transmitter systems (see Martin et al. (2000) for a review of these properties of LTP). It can be argued, however, that among all these intriguing and important characteristics, the paramount feature that defines LTP as a potential memory mechanism is its persistence over time. Thus, although short-lasting frequency potentiation of synaptic potentials was described in the hippocampus many years ago, it was not until the discovery of LTP that researchers seriously considered that a model system for studying synaptic mechanisms of mammalian memory had been established. It is curious, therefore, that despite the fundamental importance of LTP maintenance over days and weeks, relatively few studies have addressed its mechanisms and regulation. The purpose of this review is to summarize the data from experiments charting how long LTP can last, and then to address the factors that regulate how long LTP will in fact persist under various conditi...

Alterations in spatial learning and memory after forced exercise

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