METAPLASTICITY - A NEW VISTA ACROSS THE FIELD OF SYNAPTIC PLASTICITY

Over the past 20 years there has been an increasing understanding of t he properties and mechanisms underlying long-term potentiation (LTP) a nd long-term depression (LTD) of synaptic efficacy, putative learning and memory mechanisms in the mammalian brain. More recently, however, it has become apparent that synaptic activity can also elicit persiste nt neuronal responses not manifest as changes in synaptic strength. So me of these changes may nonetheless modify the ability of synapses to undergo strength changes in response to subsequent episodes of synapti c activity. This kind of activity-dependent modulatory plasticity we h ave termed ''metaplasticity''. Metaplasticity has been observed physio logically as an inhibition of LTP and concomitant facilitation of LTD by prior N-methyl-D-aspartate receptor activation or, conversely, a fa cilitation of LTP induction by prior metabotropic glutamate receptor a ctivation. The examples of metaplasticity described to date are input specific, and last as long as several hours. The mechanisms underlying such phenomena remain to be fully characterized, although some likely possibilities are an altered N-methyl-D-aspartate receptor function, altered calcium buffering, altered states of kinases or phosphatases, and a priming of protein synthesis machinery. While some details vary, experimentally observed metaplasticity bears some similarity to the ' 'sliding theshold'' feature of the Bienenstock, Cooper and Munro model of experience-dependent synaptic plasticity. Metaplasticity may serve several functions including (1) providing a way for synapses to integ rate a response across temporally spaced episodes of synaptic activity and (2) keeping synapses within a dynamic functional range, and thus preventing them from entering slates of saturated LTP or LTD. (C) 1997 Elsevier Science Ltd. All rights reserved.