Neurochemical Pattern Generation with Smart Electrical Stimulation

描述（由申请人提供）：使用智能电刺激的神经化学模式生成Pedram Mohseni 1和Paul A. Garris 2 1 Case Western Reserve University 2 Illinois州立大学在这项小额研究资助（Parent R 03）提案中，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）将合作开发下一代无线神经化学传感集成电路（IC），通过将化学模式生成的附加功能与电刺激相结合。 实时化学微传感器为研究大脑功能和病理学提供了巨大的希望。 它们的定义分析特征是通过识别释放的神经递质来询问单个神经元类型的活动的能力。 迄今为止，这种测量方式最具里程碑意义的成就可能是在碳纤维微电极（CFM）上使用快速扫描循环伏安法（FSCV）在目标导向行为期间，在大脑植入的微米级探针上以亚秒级的时间分辨率监测多巴胺。 支持这一突破性技术的无线IC也取得了长足进步。 将神经化学模式生成添加到现有的仅感测IC，实质上扩展了化学感测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、动态化学控制领域与R 03新研究技术的发展范围是一致的。 该提案的两个具体目标是：（1）开发一种神经化学传感IC，支持CFM处的FSCV，具有用于神经化学模式生成的集成电刺激能力;（2）测试和表征IC。 工程创新是IC架构将精确同步伏安法和刺激电流生成的时序，以避免时间重叠，并最大限度地减少刺激伪影干扰FSCV记录的可能性，无论何时刺激器通过外部触发器激活。 除了实验室工程评估外，还将使用不同的神经化学模式作为模板，在体外使用流动注射分析和在体内使用麻醉大鼠测试功能。 概念上的创新是传递函数驱动的神经化学模式生成和随后的验证所产生的配置文件的保真度的刺激传感IC。 在这项工作中选择多巴胺作为测试分析物是非常明智的。 多巴胺参与重要的脑功能和使人衰弱的神经病理学，适合于FSCV检测，是使用微传感器研究最多的神经递质，并且具有适合于基于时间和幅度的模式生成的完善的传递函数。 可转移到其他神经递质，微传感器的策略和应用，我们强调了一般的多功能性的建议IC作为一个更广泛的设备超出这些开发测试与多巴胺。 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和强大的补充，用于研究行为和疾病症状的神经基础，并且可以通过为最终开发用于许多人类神经病理学的新神经调节设备提供框架而具有额外的临床意义。

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.