Toward a molecular explanation for long-term potentiation.

Introduction The molecular mechanisms for long-term potentiation (LTP) may seem hopelessly complex, and no doubt the lack of clarity and concision of the immense LTP literature is a source of frustration for many (Sanes and Lichtman 1999). However, being inherently optimistic it seems to me that certain generalizations are beginning to emerge that allow an initial formulation of a molecular explanation for LTP. At this point in time we do not have in hand all the puzzle pieces concerning the molecular basis for LTP, so any explanation is by necessity incomplete and likely to contain some errors. Nevertheless, I feel it is constructive to present a working draft of a molecular model for one specific type of LTP, in the hope that it will present a useful framework for further discussion and experimentation. In this commentary I will describe several criteria that I use to narrow down the enormous LTP literature, and define certain terms commonly used and misused in the LTP literature so that we have a common vocabulary. I propose a set of criteria for inclusion of a given signal transduction cascade into a “core” mechanism for LTP and present an initial model of such a mechanism for one type of LTP. Finally, I will comment on the complexity of the molecular mechanisms of LTP induction, maintenance, and expression and point out a few emerging themes for the biochemistry of LTP. The latter serves to help manage the complexity of LTP biochemistry by generating functional categories for the molecules of LTP.

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