Modular, in-situ probes of brain chemistry

大脑化学的模块化原位探针

基本信息

批准号：
10227222
负责人：
Tod Edward Kippin
金额：
$ 52.34万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227222
关键词：
Affinity Animals Behavioral Blood Brain Brain Chemistry Brain region Chemicals Cocaine Complex Concentration measurement Data Development Disease Dopamine Dose Drug Kinetics Drug Monitoring Electrochemistry Electrodes Ensure Feedback Frequencies Genetic Hand Health Hour In Situ Intervention Measurement Measures Metabolic Methamphetamine Methods Microdialysis Molecular Molecular Analysis Monitor Morphine Abuse Neurons Neurotransmitters Noise Outcome Output Oxidation-Reduction Performance Pharmaceutical Preparations Pharmacodynamics Pharmacology Physiological Psychotropic Drugs Rattus Reporter Reporting Resolution Rodent Route Running Sensitivity and Specificity Serotonin Signal Transduction Specificity Techniques Technology Testing Time Translating Variant Vision Work aptamer awake base detection limit drug of abuse gamma-Aminobutyric Acid improved in vivo innovation insight mind control neurochemistry neuropeptide Y optogenetics particle psychobiology receptor response screening sensor success temporal measurement tool

项目摘要

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.

概括。而已建立的电化学和基于微透析的技术，用于测量药物和大脑中的神经递质对我们对大脑功能的理解无可辩驳，它们是并非没有限制。例如，当相同剂量的可卡因在5 s以上注入，而90 s 行为，代谢甚至遗传结果差异很大，表明2分钟的分辨率与先前的可卡因测量值最高度分析的最差与该药物的时间尺度相匹配很差心理生物学。更一般地，没有药物，只有少量的神经递质被测量到大脑的日期与行为上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）传感器，一个体内测量平台，不依赖于其靶标的化学或酶促反应性（从而确保普遍性）同时解决问题监视滥用药物和他们在自由移动的大脑中原位调节的神经递质的药物通常表现啮齿动物。为此，我们已经通过执行高级证明了可行性频率，多小时测量活大鼠的血液和大脑中的六个分子。利用这些初步结果，我们在这里提出了E-AB传感器的适应研究脑化学。如果成功，建议的工作将大大扩大可以实时测量的神经化学上相关的分子，并在生命中进行第二分辨率大脑，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功能和干预。