Neuronal transporters regulate glutamate clearance, NMDA receptor activation, and synaptic plasticity in the hippocampus.
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.
Scimemi
Annalisa
A
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA. scimemia@ninds.nih.gov
Tian
Hua
H
Diamond
Jeffrey S
JS
D027322:Amino Acid Transport System X-AG / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology; D050580:Excitatory Amino Acid Transporter 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D050580:Excitatory Amino Acid Transporter 3; D016194:Receptors, N-Methyl-D-Aspartate; C493399:Slc1a1 protein, mouse; D018698:Glutamic Acid