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

ECCS提案编号1407977提案标题：高密度神经记录阵列与单片集成纳米柱LED多波长光刺激Award Goal这项研究的目的是实现直接在硅基神经探针上的全色微LED阵列的单片集成，使得单个神经元的光刺激可以根据波长和强度进行专门定制。制造并测试一种可植入的神经探针，该探针能够在动物体内同时进行光学刺激和慢性电记录。光遗传学（神经元的光刺激）的最新进展为选择性地刺激或抑制单个神经元提供了新的可能性。然而，迄今为止，仍然存在对可靠的可植入工具的未满足的需求，以将光精确地递送到目标神经元，并同时记录行为动物中相应的单个神经元。在拟议的工作中，我们将开发一种可植入的探针与发光器件直接集成在光刻定义的探针柄。发光器件和记录电极的尺寸（~10微米）与神经元的尺寸相似，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显着的，因为开发的探针可以允许高精度，多个，空间上不同的输入到一个单一的神经元的局部刺激。此外，与以前的光纤方法相比，它将减轻拴系问题并最大限度地减少对动物运动的阻碍，从而允许对行为研究的光源进行实际缩放。为了实现探针柄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器件技术。发光器件的波长可以通过在发射表面上实现纳米柱结构来定制。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，具有高度特异性，可同时记录和刺激。开发的探针将打开新的窗口，了解大脑在慢性行为神经科学中的大脑映射，记忆存储，检索和可塑性等领域的功能和组织。有充分的理由希望，这些进展将导致显着改善我们的能力，以治疗人类的一些最衰弱的疾病，如帕金森氏病，癫痫和paralys.Technical AbstractRecent进展在optogenetics提供了一种新的能力，通过选择性地兴奋或抑制特定波长的光的目标神经元控制动作电位模式。然而，迄今为止，仍然存在对可靠的可植入工具的未满足的需求，以精确地递送多个波长的光，从而在细胞水平上操纵神经活动并同时监测受影响神经元的反应。这项研究的目的是实现直接在硅基神经探针上的全色微LED阵列的单片集成，以便单个神经元的光学刺激可以根据波长和强度进行专门定制。单片集成允许记录电极和LED阵列之间的精确对准，具有亚微米精度。在细胞尺寸（10 × 15微米2）中的多个微发光二极管允许以单细胞分辨率将光精确地局部递送到目标神经元。这种人造探针将被植入小鼠体内，进行一项独特的实验，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.