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Science 319 (5859): 101-104

Copyright © 2008 by the American Association for the Advancement of Science

Ongoing in Vivo Experience Triggers Synaptic Metaplasticity in the Neocortex

Roger L. Clem,1 Tansu Celikel,2* Alison L. Barth1{dagger}

Abstract: In vivo experience can occlude subsequent induction of long-term potentiation and enhance long-term depression of synaptic responses. Although a reduced capacity for synaptic strengthening may function to prevent excessive excitation, such an effect paradoxically implies that continued experience or training should not improve and may even degrade neural representations. In mice, we examined the effect of ongoing whisker stimulation on synaptic strengthening at layer 4-2/3 synapses in the barrel cortex. Although N-methyl-D-aspartate receptors were required to initiate strengthening, they subsequently suppressed further potentiation at these synapses in vitro and in vivo. Despite this transition, synaptic strengthening continued with additional sensory activity but instead required the activation of metabotropic glutamate receptors, suggesting a mechanism by which continued experience can result in increasing synaptic strength over time.

1 Department of Biological Sciences and Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
2 Department of Cell Physiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.

* Present address: Laboratory of Neural Circuits and Plasticity, University of Southern California, 3641 Watt Way, HNB 501, Los Angeles, CA 90089-2520, USA.

{dagger} To whom correspondence should be addressed. E-mail: barth{at}

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