High-Density Neural Recording Arrays with Monolithically-Integrated Nanopillar LEDs for Multi-Wavelength Optical Stimulation

ECCS道具1407977号提案标题：用于多波长光刺激的高密度神经记录阵列与单片集成纳米管LED获奖目标本研究旨在实现全色微型LED阵列直接在硅基神经探测器上的单片集成，以便可以根据波长和强度特定地定制对单个神经元的光刺激。非技术摘要本工作的目标是设计、制造和测试一种能够在动物体内同时进行光刺激和慢性电记录的植入式神经探头。光遗传学(神经元的光刺激)的最新进展为选择性地兴奋或抑制单个神经元提供了新的可能性。然而，到目前为止，对可靠的植入性工具的需求仍然没有得到满足，这些工具可以准确地将光传递到目标神经元，并同时从行为动物的相应单个神经元进行记录。在拟议的工作中，我们将开发一种植入式探头，其发光装置直接集成在光刻定义的探针柄上。发光器件和记录电极的尺寸(~10微米)类似于神经元的尺寸，为单细胞操作提供了无与伦比的分辨率。这一结果的结果将是重要的，因为所开发的探测器可以对单个神经元的多个空间上不同的输入进行高精度的局部刺激。此外，与以前的光纤方法相比，它将缓解系绳问题，并将对动物运动的阻碍降至最低，从而允许实际测量用于行为研究的光源。为了实现探头小腿上多个光源的单片集成，我们采用了为固态照明开发的显示设备技术。发光器件的波长可以通过在发射表面上实施纳米柱结构来定制。这项研究将导致开发通用工具，以访问大脑目标区域中的单个神经元，并具有同时记录和刺激的高度特异性。开发的探测器将为理解大脑在慢性行为神经科学中的大脑映射、记忆存储、提取和可塑性领域的功能和组织打开新的窗口。我们有充分的理由希望这些进展将导致我们治疗一些人类最衰弱的疾病，如帕金森氏病，癫痫和瘫痪的能力大幅提高。技术摘要光遗传学的最新进展提供了一种新的能力，通过有选择地刺激或抑制特定波长的光来刺激或抑制目标神经元，从而控制动作电位模式。然而，到目前为止，对可靠的植入性工具的需求仍然没有得到满足，这些工具可以精确地提供多个波长的光，以在细胞水平操纵神经活动，并同时监测受影响神经元的反应。本研究旨在直接在硅基神经探针上实现全彩微型LED阵列的单片集成，以便可以根据波长和强度特定地定制对单个神经元的光刺激。单片集成允许记录电极和LED阵列之间以亚微米精度精确对准。细胞维度的多个微LED(10x15微米)允许在单个细胞分辨率下将光精确地局部传递到目标神经元。这种制造的探针将被植入老鼠体内，进行一项独特的实验，以阐明记忆是如何形成和维持的。

ECCS Prop. No. 1407977Proposal Title: High-Density Neural Recording Arrays with Monolithically-Integrated Nanopillar LEDs for Multi-Wavelength Optical StimulationAward GoalThis research aims to achieve monolithic integration of full-color micro-LED arrays directly on silicon-based neural probessuch that optical stimulation of single neurons can be specifically tailored by wavelength and intensity.Nontechnical Abstract The objective of this work is to design, fabricate and test an implantable neural probe capable of simultaneous optical stimulation and chronic electrical recording in animals. Recent advancement in optogenetics (optical stimulation of neurons) promises new possibilities for selectively exciting or inhibiting individual neurons. However, to this date there is still an unmet need for reliable implantable tools to precisely deliver light to target neurons and simultaneously record from corresponding single neurons in a behaving animal. In the proposed work, we will develop an implantable probe with light emitting devices directly integrated on the lithographically defined probe shank. The size of light emitting devices and the recording electrodes have a dimension (~10 micrometers) similar to that of a neuron, offering unmatched resolution for single-cell manipulation. The outcome of this result will be significant because the developed probe can allow high precision, local stimulation of multiple, spatially distinct inputs to a single neuron. Also, it will mitigate tethering problems and minimize hindering to the animal movement as compared to the previous optical fiber approaches, allowing practical scaling of light sources for a behavioral study. To realize the monolithic integration of multiple light sources on the probe shank, we adapt the display device technologies developed for solid-state lighting. Wavelength of the light emitting devices can be tailored by implementing nanopillar structures on the emitting surface. This research will leads into the development of generic tools to access individual neurons in the target region of brain with high specificity for simultaneously recording and stimulation. The developed probes will open new windows into understanding the function and organization of the brain in the areas of brain mapping, memory storage, retrieval and plasticity in chronic behavioral neuroscience. There is good reason to hope that these advances will lead to dramatic improvements in our ability to treat some of mankind's most debilitating diseases such as Parkinson's disease, epilepsy and paralysis.Technical AbstractRecent advances in optogenetics provide a new capability to control action potential patterns by selectively exciting or inhibiting the targeted neurons by light at specific wavelengths. However, to date there is still an unmet need for reliable implantable tools to precisely deliver multiple wavelengths of light to manipulate neural activities at the cellular level and monitor the response of affected neurons simultaneously. This research aims to achieve monolithic integration of full-color micro-LED arrays directly on silicon-based neural probes such that optical stimulation of single neurons can be specifically tailored by wavelength and intensity. Monolithic integration allows precise alignment between the recording electrodes and the LED array with submicron accuracy. Multiple micro-LEDs in a cellular dimension (10 x15 micro-m2) allow precise local delivery of light to the target neurons at single cell resolution. The fabricate probe will be implanted in mice to perform a unique experiment that will elucidate how memories are formed and maintained.