Modular, in-situ probes of brain chemistry

摘要虽然已建立的用于测量药物的电化学和基于微透析的技术， 大脑中的神经递质毫无疑问有助于我们理解大脑功能，它们是 不是没有限制。例如，当相同剂量的可卡因输注超过5秒而不是90秒时， 行为，代谢，甚至遗传结果差异很大，这表明，2分钟的分辨率， 先前脑内可卡因测量的最高分辨率与药物的时间尺度匹配不良， 心理生物学更普遍的是，没有药物和只有少量的神经递质被测量， 在大脑中的日期与行为最相关的秒时间分辨率。作为回应，我们的愿景是适应 基于电化学适体（E-AB）的传感器，一种不依赖于生物传感器的体内测量平台。 其目标的化学或酶反应性（从而确保通用性），同时 监测滥用药物和它们在自由活动的大脑中原位调节的神经递质， 行为正常的啮齿动物为此，我们已经通过执行高 频率，多小时的测量超过半打分子在血液和大脑的活老鼠。 利用这些初步的结果，我们在这里提出的适应E-AB传感器的问题， 研究脑化学。如果成功，拟议的工作将大大扩大数量， 神经化学相关的分子，可以在真实的时间测量，并在生活中的第二分辨率 大脑，从而为大脑化学创造了一个新的窗口，为闭环研究提供了独特的能力 和干预。

Summary. While the established electrochemical and microdialysis-based techniques for measuring drugs and neurotransmitters in the brain have unimpeachably contributed to our understanding of brain function, they are not without limitations. For example, when the same dose of cocaine is infused over 5 s versus 90 s the behavioral, metabolic, and even genetic outcomes vary dramatically, suggesting that the 2 min resolution of the most highly resolved of prior in-brain cocaine measurements are poorly matched to timescale of the drug's psychobiology. More generally, no drugs and only a small number of neurotransmitters have been measured to date in the brain with the most behaviorally relevant seconds time resolution. In response, our vision is to adapt electrochemical aptamer-based (E-AB) sensors, an in-vivo measurement platform that does not rely on the chemical or enzymatic reactivity of its targets (thus ensuring generality), to the problem of simultaneously monitoring drugs of abuse and the neurotransmitters they modulate in situ in the brains of freely moving, normally behaving rodents. To this end, we have already demonstrated feasibility by performing the high frequency, multi-hour measurement of more than a half dozen molecules in the blood and brains of live rats. Leveraging these preliminary results we propose here the adaptation of E-AB sensors to the problem of studying of brain chemistry. If successful, the proposed work will greatly expand the number of neurochemically relevant molecules that can be measured in real time and with second resolution in the living brain, thus creating a new window into brain chemistry that provides unique capabilities for closed-loop study and intervention.