The Journal of Neuroscience, November 18, 2009, 29(46):14581-14595; doi:10.1523/JNEUROSCI.4845-09.2009
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Cellular/Molecular
Neuronal Transporters Regulate Glutamate Clearance, NMDA Receptor Activation, and Synaptic Plasticity in the Hippocampus
Annalisa Scimemi,
Hua Tian, and
Jeffrey S. Diamond
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701
Correspondence should be addressed to either Annalisa Scimemi or Jeffrey S. Diamond, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, Room 3C1006-3C1000, Bethesda, MD 20892-3701, Email: scimemia{at}ninds.nih.gov or Email: diamondj{at}ninds.nih.gov
In the mammalian brain, the specificity of excitatory synaptic transmission depends on rapid diffusion of glutamate away from active synapses and the powerful uptake capacity of glutamate transporters in astrocytes. The extent to which neuronal glutamate transporters influence the lifetime of glutamate in the extracellular space remains unclear. Here we show that EAAC1, the predominant neuronal glutamate transporter at excitatory synapses in hippocampal area CA1, buffers glutamate released during synaptic events and prolongs the time course of its clearance by astrocytes. EAAC1 does not significantly alter activation of receptors in the synaptic cleft. Instead, it reduces recruitment of perisynaptic/extrasynaptic NR2B-containing NMDARs, thereby facilitating induction of long-term potentiation by short bursts of high-frequency stimulation. We describe novel roles of EAAC1 in regulating glutamate diffusion and propose that NMDARs at different subsynaptic locations can make distinct contributions to the regulation of synaptic strength.
Received Sept. 29, 2009;
accepted Oct. 12, 2009.
Correspondence should be addressed to either Annalisa Scimemi or Jeffrey S. Diamond, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, Room 3C1006-3C1000, Bethesda, MD 20892-3701, Email: scimemia{at}ninds.nih.gov or Email: diamondj{at}ninds.nih.gov