Smith Samantha K, Lee Christie A, Dausch Matthew E, Horman Brian M, Patisaul Heather B, McCarty Gregory S, Sombers Leslie A
Department of Chemistry, ‡Department of Biological Sciences, North Carolina State University , Raleigh, North Carolina 27695-8204, United States.
ACS Chem Neurosci. 2017 Feb 15;8(2):272-280. doi: 10.1021/acschemneuro.6b00363. Epub 2017 Jan 17.
Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.
脑血流量确保将葡萄糖等营养物质输送到代谢需求增加的脑区。然而,关于体内神经元激活期间离散位置处快速的葡萄糖动态变化,我们所知甚少。急性接触多种滥用物质会引发纹状体中多巴胺释放和神经元激活;然而,纹状体中葡萄糖的伴随变化在很大程度上仍不清楚。最近的进展将快速扫描循环伏安法与葡萄糖氧化酶修饰的碳纤维微电极相结合,能够在哺乳动物大脑中以亚秒级时间分辨率测量葡萄糖动态变化。这项工作评估了几种波形,以便在单个记录位点首次同时检测内源性葡萄糖和多巴胺。发现这两种分子,一种具有电活性,一种不具有电活性,在中脑电刺激和全身注射可卡因/雷氯必利后会在背侧纹状体中波动。数据揭示了这些物质在纹状体微环境中的逐秒动态变化,并直接证明了葡萄糖可用性与增加的代谢需求之间的耦合。这项工作提供了一个基础,将能够详细研究在正常条件下以及在药物滥用和成瘾的动物研究中调节脑血流量与代谢需求耦合的局部机制。