RT Journal Article SR Electronic T1 Neuronal Transporters Regulate Glutamate Clearance, NMDA Receptor Activation, and Synaptic Plasticity in the Hippocampus JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 14581 OP 14595 DO 10.1523/JNEUROSCI.4845-09.2009 VO 29 IS 46 A1 Scimemi, Annalisa A1 Tian, Hua A1 Diamond, Jeffrey S. YR 2009 UL http://www.jneurosci.org/content/29/46/14581.abstract AB 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.