Neurochemical Pattern Generation with Smart Electrical Stimulation

通过智能电刺激生成神经化学模式

• 批准号: 8225597
• 负责人: PAUL A GARRIS
• 金额: $ 8.34万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8225597
• 关键词: Achievement; Address; Agonist; Animals; Architecture; Automobile Driving; Basic Science; Behavior; Behavioral; Behavioral Paradigm; Biomedical Research; Brain; Characteristics; Chemical Dynamics; Chemicals; Clinical; Computers; Detection; Development; Devices; Dimensions; Disease; Dopamine; Electric Stimulation; Electrical Engineering; Engineering; Equipment; Evaluation; Feedback; Flow Injection Analysis; Funding; Future; Generations; Goals; Human; Illinois; Implant; In Vitro; Investigation; Laboratory Animals; Link; Measurement; Measures; Medicine; Microelectrodes; Modality; Molecular; Monitor; Morphologic artifacts; Motor; Nature; Neurobiology; Neuromodulator; Neurons; Neurotransmitters; Parents; Pathology; Pattern; Performance; Physiological; Public Health; Rattus; Research; Research Project Grants; Resolution; Resources; Scanning; Scientist; Semiconductors; Signal Transduction; Stimulus; Symptoms; Synaptic plasticity; Techniques; Technology; Telemetry; Testing; Therapeutic; Time; United States National Institutes of Health; Universities; Weight; Wireless Technology; Work; awake; base; carbon fiber; design; in vitro testing; in vivo; innovation; meetings; metal oxide; multidisciplinary; neurochemistry; neuropathology; neuroprosthesis; neuroregulation; neurotransmitter release; next generation; novel; programs; relating to nervous system; research and development

DESCRIPTION (provided by applicant): Neurochemical Pattern Generation with Smart Electrical Stimulation Pedram Mohseni1 and Paul A. Garris2 1 Case Western Reserve University 2 Illinois State University In this Small Research Grant (Parent R03) proposal, an electrical engineer/computer scientist (PI Mohseni) and a neurobiologist/analytical chemist (PI Garris) will collaborate to develop the next generation of wireless neurochemical sensing integrated circuits (ICs) by incorporating the additional functionality of chemical pattern generation with electrical stimulation. Real-time chemical microsensors hold great promise for investigating brain function and pathology. Their defining analytical characteristic is the capability to interrogate the activity of a single neuron type, by virtue of identifying the released neurotransmitter. Perhaps the most monumental achievement to date with this measurement modality is dopamine monitoring with subsecond temporal resolution at a brain-implanted, micron-sized probe during goal-directed behavior using fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM). Great strides have also been made in wireless ICs supporting this ground-breaking technology. Adding neurochemical pattern generation to extant sensing- only ICs substantively expands the utility of chemical sensing ICs, ultimately laying foundational work for future closed-loop devices. We submit that extending passive chemical measurements to the realm of high-precision, dynamic chemical control is consistent with the R03 scope of development of new research technology. The two specific aims of this proposal are to: (1) develop a neurochemical sensing IC supporting FSCV at a CFM with integrated electrical stimulation capability for neurochemical pattern generation; (2) test and characterize the IC. The engineering innovation is that IC architecture will precisely synchronize the timing of voltammetry and stimulus current generation to avoid temporal overlap and minimize the possibility of stimulus artifacts interfering with FSCV recordings, whenever the stimulator is activated via an external trigger. In addition to benchtop engineering assessment, functionality will be tested in vitro with flow injection analysis and in vivo with anesthetized rats, using diverse neurochemical patterns as templates. The conceptual innovation is transfer function-driven neurochemical pattern generation and subsequent verification of the fidelity of the generated profile by the stimulating-sensing IC. Selection of dopamine as the test analyte in this work is very judicious. Involved in important brain functions and debilitating neuropathologies, dopamine is amenable to FSCV detection, is the most studied neurotransmitter using microsensors, and has well-established transfer functions suitable for time- and amplitude-based pattern generation. Transferable to other neurotransmitters, microsensor strategies, and applications, we emphasize the general versatility of the proposed IC as a more wide-ranging device beyond these development tests with dopamine. Thus, in the long term, the proposed IC will provide an innovative and powerful addition to the neurobiology toolkit for investigating the neural underpinnings of behavior and disease symptoms, and could have additional clinical bearing by providing the framework for ultimately developing new neuromodulation devices for many human neuropathologies. PUBLIC HEALTH RELEVANCE: Neurochemical Pattern Generation with Smart Electrical Stimulation Pedram Mohseni1 and Paul A. Garris2 1 Case Western Reserve University 2 Illinois State University Relevance to Public Health: This project will develop an advanced integrated circuit for measuring and controlling neurotransmitter levels in the brain of laboratory animals. This technology will advance basic biomedical research and the development of neuroprostheses for treating human neuropathologies.

DESCRIPTION (provided by applicant): Neurochemical Pattern Generation with Smart Electrical Stimulation Pedram Mohseni1 and Paul A. Garris2 1 Case Western Reserve University 2 Illinois State University In this Small Research Grant (Parent R03) proposal, an electrical engineer/computer scientist (PI Mohseni) and a neurobiologist/analytical chemist (PI Garris) will collaborate to develop the next generation of wireless neurochemical sensing通过将化学模式产生的附加功能与电刺激结合在一起，整合电路（ICS）。 实时化学微传感器对研究大脑功能和病理学有很大的希望。 它们的定义分析特征是通过识别释放的神经递质来审问单个神经元类型的活性的能力。 迄今为止，通过这种测量方式，最巨大的成就是在目标指导行为期间使用快速扫描的环环（FSCV）以碳纤维微电极（CFM）在目标定向行为的情况下，在脑植入脑植入的微米大小的探针下进行多巴胺监测。 在支持这项开创性技术的无线IC中也取得了长足的进步。 将神经化学模式的产生添加到现有的感应中 - 只有IC实质性地扩大了化学传感IC的实用性，最终为未来的闭环设备奠定了基础工作。 我们认为，将被动化学测量扩展到高精度领域，动态化学控制与新研究技术开发的R03范围一致。 该提案的两个具体目的是：（1）在CFM处开发一个神经化学感应IC，具有整合的电刺激能力，以产生神经化学模式的产生； （2）测试并表征IC。 工程创新是，IC架构将精确同步伏安法和刺激当前一代的时机，以避免时间重叠并最大程度地减少刺激伪像的可能性，每当刺激器通过外部扳机激活时，刺激造影量会干扰FSCV录制。 除了台式工程评估外，还将通过流量注射分析和在体内与麻醉大鼠在体外测试功能，并使用各种神经化学模式作为模板。 概念创新是传递功能驱动的神经化学模式产生以及随后通过刺激感应的IC对生成曲线的保真度的验证。 在这项工作中，选择多巴胺作为测试分析物是非常明智的。 参与重要的大脑功能和使神经病理学的衰弱，多巴胺可容纳FSCV检测，是使用微传感器研究最多的神经递质，并且具有适合基于时间和振幅基于时间和幅度模式生成的完善的传递功能。 我们可以转移到其他神经递质，微传感器策略和应用中，我们强调了拟议的IC作为多巴胺开发测试以外的更广泛的设备的一般多功能性。 因此，从长远来看，所提出的IC将为神经生物学工具包提供创新且有力的补充，用于研究行为和疾病症状的神经基础，并可以通过为许多人类神经病理提供最终开发新的神经调节设备的框架来具有额外的临床轴承。 公共卫生相关性：智能电气刺激的神经化学模式产生PEDRAM MOHSENI1和PAUL A. GARRIS2 1案例西部储备大学2伊利诺伊州立大学与公共卫生的相关性：该项目将开发一个高级综合电路，用于测量和控制实验室动物大脑中神经递质水平。 这项技术将推进基本的生物医学研究，并发展用于治疗人类神经病理学的神经假体。