Extracellular Glutamate in the Nucleus Accumbens Is Nanomolar in Both Synaptic and Non-synaptic Compartments.
Extracellular Glutamate in the Nucleus Accumbens Is Nanomolar in Both Synaptic and Non-synaptic Compartments.
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DOI：
10.1016/j.celrep.2017.02.047
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发表时间：
2017-03-14
期刊：
影响因子：
8.8
通讯作者：
Jahr CE
中科院分区：
文献类型：
--
作者：
Chiu DN;Jahr CE
在中枢神经系统中，谷氨酸是阶段性和紧张性释放到细胞外空间，必须清除兴奋性氨基酸转运蛋白（EAAT），以防止兴奋性毒性积累。然而，关于功能稳态浓度仍然存在不确定性，估计值从几十纳摩尔到几十微摩尔不等。调和这些不同的值的努力导致了一种假设，即细胞外空间由不同的隔室组成，其中基础谷氨酸浓度独立维持。我们使用电生理学和双光子Ca2+成像来测试这一假设在核的脑桥（NAc），在那里已经提出，微摩尔细胞外谷氨酸是必要的正常功能。我们发现，突触谷氨酸的平均浓度是纳摩尔，与以前的电生理估计。此外，当谷氨酸摄取被抑制时，这是正确的，表明细胞外谷氨酸不被EAAT区室化。谷氨酸存在于神经元周围的细胞外空间，但尚不清楚突触和非突触区域的稳态浓度是否相同。Chiu和Jahr表明，突触间隙内外的基础细胞外谷氨酸是纳摩尔的。
In the CNS, glutamate is both phasically and tonically released into the extracellular space, and must be removed by excitatory amino acid transporters (EAATs) to prevent excitotoxic accumulation. There remains uncertainty, however, regarding the functional steady-state concentration, with estimates ranging from tens of nanomolar to tens of micromolar. Efforts to reconcile these disparate values have led to a hypothesis that the extracellular space is comprised of distinct compartments in which basal glutamate concentrations are maintained independently. We used electrophysiology and two-photon Ca2+ imaging to test this hypothesis in the nucleus accumbens (NAc), where it has been proposed that micromolar extracellular glutamate is necessary for normal function. We found that the average concentration of synaptic glutamate is nanomolar, in agreement with previous electrophysiological estimates. Furthermore, this held true when glutamate uptake was inhibited, indicating that extracellular glutamate is not compartmentalized by EAATs. Glutamate is present in the extracellular space surrounding neurons, but it is unclear whether the steady-state concentration in synaptic and non-synaptic areas is the same. Chiu and Jahr show that basal extracellular glutamate is nanomolar, both in- and outside the synaptic cleft.