A Closed-Loop Microsystem for Neuromodulation of Reward Circuitry

用于奖励电路神经调节的闭环微系统

• 批准号: 8599081
• 负责人: PAUL A GARRIS
• 金额: $ 20.18万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8599081
• 关键词: Addictive Behavior; Amphetamines; Analytical Chemistry; Attention; Attention deficit hyperactivity disorder; Automobile Driving; Award; Basic Science; Biomedical Research; Brain; Brain region; Chemicals; Clinical; Complex; Computers; Cues; Data; Deep Brain Stimulation; Development; Devices; Dopamine; Drug Addiction; Drug abuse; Electric Stimulation; Electrical Engineering; Engineering; Evaluation; Exhibits; Feedback; Flow Injection Analysis; Fostering; Foundations; Future; Goals; Illinois; Implant; In Vitro; Investigation; Laboratory Animals; Link; Measurement; Measures; Methods; Microelectrodes; Modeling; Molecular; Monitor; Narcolepsy; Neurobiology; Neurons; Neurotransmitters; Outcome; Pharmaceutical Preparations; Phase; Physiologic pulse; Process; Public Health; Rattus; Research; Research Support; Resolution; Role; Scanning; Scientist; Semiconductors; Signal Transduction; Synapses; Synaptic plasticity; Techniques; Technology; Testing; Therapeutic; Time; Training; Transgenic Animals; United States National Institutes of Health; Universities; Work; addiction; base; carbon fiber; clinical efficacy; computer science; computerized data processing; doctoral student; dopaminergic neuron; drug of abuse; high risk; in vivo; innovation; metal oxide; microstimulation; microsystems; multidisciplinary; neurochemistry; neuroprosthesis; neuroregulation; novel; optogenetics; prevent; programs; psychostimulant; public health relevance; recidivism; reconstruction; relating to nervous system; research study; reward circuitry; reward processing

DESCRIPTION (provided by applicant): A Closed-Loop Microsystem for Neuromodulation of Reward Circuitry Pedram Mohseni1 and Paul A. Garris2 1 Case Western Reserve University 2 Illinois State University While great strides have been made in our understanding of the basic neurobiology of addiction, many outstanding questions still remain. There is also a grave necessity to develop new treatments, as current options exhibit high recidivism. For good reason, particular attention has focused on the role of dopamine neurons in compulsory drug taking and addictive behavior. One emergent hypothesis is that abused substances usurp reward-processing circuits by hyperactivating phasic dopamine signaling, which leads to altered synaptic plasticity and the overvaluation of cues predicting drug availability. Driving the pursuit of this potentially unifying hypothesis are recent technical advances in microsensors, transgenic animals, and optogenetics. Collectively, these powerful approaches permit high-fidelity dopamine monitoring and ultra-fine molecular control over dopamine neurons and their targets. However, there is a dearth in the current state of technology for dynamic, state-dependent control. Such technology would actively link neuromonitoring and neurostimulation in closed-loop manner to permit extant neural activity and a priori criteria determine the desired outcome. The long-term objective of this research is thus to realize closed-loop devices supporting research in drug abuse and clinical therapies for treating addiction. To this end, an electrical engineer/computer scientist (PI Mohseni) and a neurobiologist/analytical chemist (PI Garris) will collaborate on the present Cutting-Edge Basic Research Awards (CEBRA) proposal to develop a computation and control integrated circuit (IC) for such linking of neuromonitoring and neurostimulation. This IC will incorporate fast- scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM), a state-of-the-art neuromonitoring technique with exquisite temporal, spatial, and chemical resolution, and principal component regression (PCR), a chemometrics approach for resolving single analytes from complex neurochemical profiles. The three specific aims are to: (1) develop a sensing, computation, and control IC supporting FSCV at a CFM; (2) test and characterize the IC; (3) pilot dopamine-sensing-based feedback control with the IC for neutralizing activated phasic dopamine signaling. We submit that developing this IC is a transformative step for addiction research, by laying the foundation for novel implantable microsystems supporting applications in biomedical research and ultimately for smart therapeutic neuroprostheses in the clinical realm. Feedback control based on the ability of FSCV and PCR to interrogate the neurochemical activity of a single neuron-type also represents a significant technical advance toward the development of closed-loop devices. This research is additionally innovative, because an IC for neurochemical feedback control has not been realized, and the proposed IC will be capable of modulating both static and dynamic neurochemical activity and accommodating a broad repertoire of analytes important in addiction. This project will also train one doctoral student each in the fields of electrical engineering-computer science and neurobiology-analytical chemistry during its two-year duration.

描述（由申请人提供）：奖励电路神经调节的闭环微系统 Pedram Mohseni1 和 Paul A. Garris2 1 凯斯西储大学 2 伊利诺伊州立大学 虽然我们对成瘾的基本神经生物学的理解已经取得了巨大进步，但仍然存在许多悬而未决的问题。由于目前的选择表现出很高的累犯率，因此迫切需要开发新的治疗方法。有充分的理由，人们特别关注多巴胺神经元在强制吸毒和成瘾行为中的作用。一种新的假设是，滥用物质通过过度激活阶段性多巴胺信号传导来侵占奖励处理回路，从而导致突触可塑性改变和对预测药物可用性的线索的高估。驱动追求 这一潜在统一假设的体现是微传感器、转基因动物和光遗传学方面的最新技术进步。总的来说，这些强大的方法可以对多巴胺神经元及其目标进行高保真多巴胺监测和超精细分子控制。然而，目前动态的、状态相关的控制技术还很缺乏。这种技术将以闭环方式主动连接神经监测和神经刺激，以允许现有的神经活动和先验标准确定所需的结果。因此，这项研究的长期目标是实现支持药物滥用研究和成瘾临床治疗的闭环设备。为此，电气工程师/计算机科学家 (PI Mohseni) 和神经生物学家/分析化学家 (PI Garris) 将就当前的尖端基础研究奖 (CEBRA) 提案进行合作，开发用于神经监测和神经刺激连接的计算和控制集成电路 (IC)。该 IC 将在碳纤维微电极 (CFM) 上集成快速扫描循环伏安法 (FSCV)，这是一种最先进的神经监测技术，具有精致的时间、空间和化学分辨率，以及主成分回归 (PCR)，这是一种从复杂的神经化学谱中解析单一分析物的化学计量学方法。这三个具体目标是：(1) 开发支持 CFM FSCV 的传感、计算和控制 IC； (2) 测试并表征 IC； (3) 使用 IC 进行基于多巴胺传感的反馈控制，以中和激活的相位多巴胺信号传导。我们认为，开发这种 IC 是成瘾研究的变革性一步，为支持生物医学研究应用的新型可植入微系统奠定了基础，并最终为临床领域的智能治疗性神经假体奠定了基础。基于 FSCV 和 PCR 询问单个神经元类型的神经化学活性的能力的反馈控制也代表了闭环设备开发的重大技术进步。这项研究还具有创新性，因为用于神经化学反馈控制的 IC 尚未实现，而所提出的 IC 将能够调节静态和动态神经化学活性，并容纳对成瘾很重要的广泛分析物。该项目还将在两年内培养电气工程-计算机科学和神经生物学-分析化学领域的博士生各一名。