Modular, in-situ probes of brain chemistry

总结。虽然已建立的基于电化学和微渗析的药物和药物检测技术 大脑中的神经递质对我们了解大脑功能做出了无懈可击的贡献，它们是 并不是没有限制。例如，当注射相同剂量的可卡因时，S超过5次，而S超过90次。 行为、代谢甚至遗传结果差异很大，这表明2分钟的分辨率 之前最高分辨率的脑内可卡因测量结果与药物的时间刻度很难匹配 心理生物学。更广泛地说，没有药物，只有少量的神经递质被测量到 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 基于电化学适配子(E-AB)的传感器，这是一个不依赖于 其靶标的化学或酶反应(从而确保通用性)，对同时存在的问题 监测滥用药物及其在自由活动的大脑中原位调节的神经递质， 正常行为的啮齿动物。为此，我们已经通过执行高 对活着的大鼠血液和大脑中六个以上分子的频率进行数小时测量。 利用这些初步结果，我们建议使E-AB传感器适应以下问题 研究大脑化学。如果成功，拟议的工作将极大地扩大 与神经化学相关的分子，可在活体中以秒分辨率实时测量 大脑，从而创造了一个了解大脑化学的新窗口，为闭环系统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.