Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex.
Rapid microelectrode measurements and the origin and regulation of extracellular glutamate in rat prefrontal cortex.
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DOI：
10.1111/j.1471-4159.2010.07066.x
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发表时间：
2010-12
影响因子：
4.7
通讯作者：
Gerhardt GA
中科院分区：
文献类型：
--
作者：
Hascup ER;Hascup KN;Stephens M;Pomerleau F;Huettl P;Gratton A;Gerhardt GA
前额叶皮质(PFC)中的谷氨酸在包括精神分裂症、成瘾和焦虑在内的多种精神疾病中起着重要作用。以前对PFC谷氨酸介导的功能的研究使用了一些技术，提出了谷氨酸的神经元来源与星形细胞来源的问题。本研究使用基于酶的微电极阵列(MEA)来监测清醒大鼠PFC中静息状态下的谷氨酸水平。局部应用的药物被用来试图区分静息谷氨酸信号的神经元或神经胶质成分。局部应用河豚毒素(TTX；钠通道阻滞剂)后，静息谷氨酸水平显著下降(~40%)。此外，局部应用ω-conooxin(~50%；钙通道阻滞剂)和mGluR⅔激动剂LY379268(~20%)显著降低细胞外谷氨酸，而mGluR⅔拮抗剂LY341495显著增加(~40%)，所有这些效应都与神经元对静息谷氨酸水平的巨大贡献一致。局部应用D，L-苏氨酸-β-苄氧天冬氨酸(TBOA；谷氨酸转运蛋白抑制剂)可使细胞外谷氨酸水平增加约120%，支持主要位于胶质细胞的兴奋性氨基酸转运体调节细胞外谷氨酸的清除。有趣的是，局部应用(S)-4-羧基苯甘氨酸(CPG；半胱氨酸/谷氨酸逆向转运蛋白抑制剂)，与载体对照组相比，细胞外谷氨酸产生了微小的、非显著的双相变化。最后，预先给药TTX完全阻断了谷氨酸对尾巴挤压应激的反应。综上所述，这些结果支持MEA技术测量的大鼠PFC静息谷氨酸水平至少有40%-50%来自神经元。此外，这些数据支持生理诱发事件中依赖于冲动流的谷氨酸释放完全是神经元来源的。
Glutamate in the prefrontal cortex (PFC) plays a significant role in several mental illnesses, including schizophrenia, addiction and anxiety. Previous studies on PFC glutamate-mediated function have used techniques that raise questions on the neuronal vs. astrocytic origin of glutamate. The present studies used enzyme-based microelectrode arrays (MEAs) to monitor second-by-second resting glutamate levels in the PFC of awake rats. Locally-applied drugs were employed in an attempt to discriminate between the neuronal or glial components of the resting glutamate signal. Local application of tetrodotoxin (TTX; sodium channel blocker), produced a significant (~40%) decline in resting glutamate levels. In addition significant reductions in extracellular glutamate were seen with locally-applied ω-conotoxin (MVIIC; ~50%; calcium channel blocker), and the mGluR⅔ agonist, LY379268 (~20%), and a significant increase with the mGluR⅔ antagonist LY341495 (~40%), effects all consistent with a large neuronal contribution to the resting glutamate levels. Local administration of D,L-threo-β-benzyloxyaspartate (TBOA; glutamate transporter inhibitor) produced an ~120% increase in extracellular glutamate levels, supporting that excitatory amino acid transporters, which are largely located on glia, modulate clearance of extracellular glutamate. Interestingly, local application of (S)-4-carboxyphenylglycine (CPG; cystine/glutamate antiporter inhibitor), produced small, non-significant bi-phasic changes in extracellular glutamate versus vehicle control. Finally, pre-administration of TTX completely blocked the glutamate response to tail pinch stress. Taken together, these results support that PFC resting glutamate levels in rats as measured by the MEA technology are at least 40-50% derived from neurons. Furthermore, these data support that the impulse flow-dependent glutamate release from a physiologically-evoked event is entirely neuronally derived.
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影响因子：
4.7
作者：
BRABET, I;MARY, S;PIN, JP
通讯作者：
PIN, JP
影响因子：
13.1
作者：
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通讯作者：
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作者：
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Ballini, Chiara;Della Corte, Laura;Giovannini, Maria Grazia
通讯作者：
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4.7
作者：
Barger, Steven W.;Goodwin, Mary E.;Beggs, Marjorie L.
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