The plasticity-pathology continuum: Defining a role for the LTP phenomenon

Long-term potentiation (LTP) is the most widely studied form of neuroplasti city and is believed by many in the field to be the substrate for learning and memory. For this reason, an understanding of the mechanisms underlying LTP is thought to be of fundamental importance to the neurosciences, but a definitive linkage of LTP to learning or memory has not been achieved, Much of the correlational data used to support this claim is ambiguous and cont roversial, precluding any solid conclusion about the functional relevance o f this often artificially induced form of neuroplasticity, In spite of this fact, the belief that LTP is a mechanism subserving learning and/or memory has become so dominant in the field that the investigation of other potent ial roles or actions of LTP-like phenomena in the nervous system has been s eriously hindered. The multiple subtypes of the phenomena and the myriad mo lecules apparently involved in these subtypes raise the possibility that ob served forms of LTP may represent very different types of modification even ts, with vastly different consequences for neural function and survival. A relationship between LTP and neuropathology is suggested in part by the fac t that many of the molecular processes involved in LTP induction or mainten ance are the same as those activated during excitotoxic events in neurons. In addition, some LTP subtypes are clearly induced by pathological stimuli, e.g., anoxic LTP, Such data raise the possibility that LTP is part of a co ntinuum of types of neural modification, some leading to beneficial alterat ions such as may occur in learning and others that may be primarily patholo gical in nature, as in kindling and excitotoxicity. In this article, we int roduce a plasticity-pathology continuum model that is designed to place the various forms of neural modification into proper context. In vitro and kin dling receptor regulation studies are used to provide a basis for evaluatin g the specific synaptic/cellular response modification along the continuum of events, from beneficial to detrimental, that will be induced by a partic ular stimulus. (C) 1999 Wiley-Liss, Inc.