Large-Scale Electrophysiological Recording and Optogenetic Control System

 描述(申请人提供)：为了更好地了解调节人类认知功能的神经机制，需要新的方法和技术来极大地扩展记录和操纵灵长类大脑广泛区域中大量神经元活动的能力。在过去的5-10年里，我们的团队在研究非人类灵长类动物的神经回路方面取得了两个主要进展。我们已经开发和改进了大规模记录猴子神经活动的新方法，并将这些技术商业传播到北美、欧洲和亚洲的实验室(Goodell和Gray)。我们还利用光遗传学和电生理学相结合的方法(Sheinberg和Pesaran)，实施了最先进的方法来操纵行为猴子的神经回路中的活动。现在，我们寻求提炼、优化和结合这些技术，以扩大它们的范围、可靠性和效率，并加速它们的发展和向更广泛的神经科学界传播。第一个具体目标是改进和优化用于长期植入的微驱动系统 以及对数百个微电极的独立控制，这些微电极能够记录大脑深处任何区域的神经元活动，表现出非人类灵长类动物的行为。第二个具体目标是开发和改进一种微驱动系统，该系统能够从大量独立可移动的光学电极中对神经元活动进行光遗传控制和电生理测量，这些光学电极能够在表现非人类灵长类动物行为时瞄准整个大脑深处的任何区域。为了实现这些目标，我们将进行两项密切协调的设计、开发和研究工作，以显著提高当前技术的能力，并在两个独立的实验室中严格测试清醒的猴子。由此产生的技术将使研究人员能够操纵和测量行为猴子的大规模电路中活动的时空模式，从而测试远远超出现有方法范围的神经电路功能假说。

 DESCRIPTION (provided by applicant): In order to gain a greater understanding of the neural mechanisms that mediate human cognitive function new approaches and technologies are needed to dramatically expand the ability to record and manipulate the activity of large numbers of neurons throughout widespread areas of the primate brain. Over the past 5-10 years, our groups have made two major advances in the study of neural circuits in non-human primates. We have developed and refined new methods for the large-scale recording of neuronal activity in behaving monkeys and commercially disseminated these technologies to laboratories throughout North America, Europe and Asia (Goodell and Gray). We have also implemented state-of-the-art methods for manipulating activity in neural circuits in behaving monkeys using a combination of optogenetics and electrophysiology (Sheinberg and Pesaran). Now we seek to refine, optimize and combine these technologies to expand their scope, reliability and efficiency, and accelerate their development and dissemination to the wider neuroscientific community. The first specific aim is to refine and optimize a microdrive system for the long-term implantation and independent control of hundreds of microelectrodes capable of recording neuronal activity from any region throughout the depth of the brain in behaving non-human primates. The second specific aim is to develop and refine a microdrive system that enables the optogenetic control and electrophysiological measurement of neuronal activity from large numbers of independently movable optrodes capable of targeting any region throughout the depth of the brain in behaving non-human primates. To accomplish these objectives, we will conduct two lines of closely coordinated design, development and research efforts to dramatically improve the capability of the current technology and to rigorously test the instruments in awake, behaving monkeys in two separate laboratories. The resulting technology will enable researchers to manipulate and measure spatiotemporal patterns of activity in large-scale circuits in behaving monkeys and thereby test hypotheses of neural circuit function that are well beyond the scope of existing methods.