Technological advances for the neuromodulation of the spinal cord

脊髓神经调节的技术进步

• 批准号: RGPIN-2022-05187
• 负责人: Shahriari, Dena
• 金额: $ 1.89万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761895
• 关键词: Technological; advances; neuromodulation; spinal; cord; Technological; advances; neuromodulation; spinal; cord

The roles of different neuronal types in the spinal cord of the neural circuitry controlling motor function are only partially understood. New technologies may be needed to better understand the spinal circuitry in its normal function or its plasticity after partial lesions. Neuromodulation is a technique that primarily uses electrical stimulation to re-wire and strengthen spared neural connections and has offered some understanding of neural relays. However, due to the nature of electrical stimulation, which activates all neuronal types where the stimulus is applied, as well as challenges in recording neural or muscle activity during electrical stimulation, it is difficult to understand the roles of different neuronal types. Neural stimulation using light instead of electricity has the potential to overcome this challenge. Optical stimulation of neurons was initially introduced by viral transduction of a targeted group of cells to express opsins to respond to light - termed optogenetics. Optogenetics has revolutionized our knowledge of the brain circuitry, but its power is yet to be harnessed in the spinal cord and the peripheral nerves due to the technological limitations of chronic and autonomous light delivery to these highly mobile regions. My proposed research program aims to overcome these technological gaps and develop a fundamental understanding of the effects of stimulating or silencing targeted groups of neurons. My central hypothesis is that exciting or inhibiting specific neuronal types will allow us to understand the roles of different neurons on muscle activity. Being at the intersection of materials science and electrical engineering, my team and I will develop the tools to enable optical stimulation of the spinal cord coupled with wireless electromyography (EMG) signal acquisition. The technology will include flexible neural probes with micro light-emitting diodes (µLED) of different wavelengths that can be placed over the spinal cord/peripheral nerves in animals. The probes will be connected to a printed circuit board (PCB) with a microcontroller that is programmed to pulsate the µLEDs at parameters already optimized for the implemented opsins. The PCB is connected to a wirelessly rechargeable battery enabling the device to be fully implantable. The system can be modified to be wirelessly reprogrammable to change the light pulsation parameters on-demand. We will also develop electrodes and tools to wirelessly obtain EMG signals. The in vivo feasibility of the tools will be evaluated in a limited number of animal subjects. Our system will therefore enable a platform to simultaneously excite and/or inhibit multiple types of neurons and study their roles in muscle activity and neuromodulation. Our research program will therefore propel Canada to the forefront of research in fundamental understanding of neural relays beyond the brain.

仅部分理解了控制运动运动功能的神经元电路脊髓中不同神经元类型的作用。可能需要新技术以更好地了解其正常功能或部分讲座后的可塑性的脊柱回路。神经调节是一项主要使用电气模拟来重新分割和加强避免神经元连接的技术，并提供了对神经元继电器的一些了解。但是，由于电刺激的性质，它激活了应用刺激的所有神经元类型，以及在电刺激过程中记录神经元或肌肉活性的挑战，因此很难理解不同神经元类型的作用。使用光而不是电的神经刺激有可能克服这一挑战。最初，通过对靶向细胞的病毒翻译来表达神经元的光学刺激，以表达对光的光遗传学反应。光遗传学彻底改变了我们对脑电路的了解，但是由于慢性光和自主光向传递到这些高度移动区域的技术限制，其功率尚未在脊髓和周围神经中利用。我提出的研究计划旨在克服这些技术差距，并对刺激或沉默的针对性神经元的影响产生基本理解。我的中心假设是，令人兴奋或抑制特定的神经元类型将使我们能够理解不同神经元在肌肉活动中的作用。在材料科学与电气工程的交汇处，我和我的团队将开发工具，以使脊髓与无线肌电图（EMG）信号获取相结合。该技术将包括可在动物中脊髓/外围神经上放置的不同波长的微光发光二极管（µLED）的柔性神经元问题。这些问题将通过微控制器连接到打印的电路板（PCB），该微控制器被编程为以已针对已实现的OPSIN进行优化的参数进行脉冲。 PCB连接到无线可充电电池，使设备能够完全植入。可以对系统进行修改以无线重编程以按需更改光脉动参数。我们还将开发电极和工具以无线获取EMG信号。工具的体内可行性将在有限数量的动物受试者中进行评估。因此，我们的系统将使平台能够简单地激发和/或抑制多种类型的神经元，并研究其在肌肉活动和神经调节中的作用。因此，我们的研究计划将使加拿大在对大脑以外的神经元中继的基本了解方面置于研究的最前沿。