Scimemi Annalisa, Tian Hua, Diamond Jeffrey S
Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA.
J Neurosci. 2009 Nov 18;29(46):14581-95. doi: 10.1523/JNEUROSCI.4845-09.2009.
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.
在哺乳动物大脑中，兴奋性突触传递的特异性取决于谷氨酸从活跃突触快速扩散以及星形胶质细胞中谷氨酸转运体强大的摄取能力。神经元谷氨酸转运体对细胞外空间中谷氨酸寿命的影响程度尚不清楚。在此，我们表明，EAAC1作为海马体CA1区兴奋性突触中主要的神经元谷氨酸转运体，可缓冲突触活动期间释放的谷氨酸，并延长星形胶质细胞清除谷氨酸的时间进程。EAAC1不会显著改变突触间隙中受体的激活。相反，它会减少突触周围/突触外含NR2B的NMDAR的募集，从而促进高频刺激短脉冲诱导的长时程增强。我们描述了EAAC1在调节谷氨酸扩散方面的新作用，并提出不同突触下位置的NMDAR对突触强度的调节可做出不同贡献。
