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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 99/2/524    most recent 01169.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Harris, A. Z. Articles by Pettit, D. L. PubMed PubMed Citation Articles by Harris, A. Z. Articles by Pettit, D. L.

Recruiting Extrasynaptic NMDA Receptors Augments Synaptic Signaling

Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York

Submitted 22 October 2007; accepted in final form 30 November 2007

N-Methyl-D-aspartate receptor (NMDAR) activation may promote cell survival or initiate cell death, with the outcome dependent on whether synaptic or extrasynaptic receptors are activated. Similarly, this differential activation has been proposed to govern the direction of plasticity. However, the physiological parameters necessary to activate extrasynaptic NMDARs in brain slices remain unknown. Using the irreversible use-dependent NMDAR antagonist MK-801 to isolate extrasynaptic NMDARs, we have tested the ability of short-stimulation trains from 5 to 400 Hz to activate these receptors on CA1 hippocampal slice pyramidal neurons. Frequencies as low as 25 Hz engage extrasynaptic NMDARs, with maximal activation at frequencies between 100 and 200 Hz. Since similar bursts of synaptic input occur during exploratory behavior in rats, our results demonstrate that "extrasynaptic" NMDARs regularly participate in synaptic transmission. Further, 175-Hz-stimulation trains activate all available synaptic and extrasynaptic dendritic NMDARs, suggesting these NMDARs act as synaptic receptors as needed, transiently increasing synaptic strength. Thus extrasynaptic NMDARs play a vital role in synaptic physiology, calling into question their status as "extrasynaptic."