Technological advances for the neuromodulation of the spinal cord

不同类型的神经元在脊髓中控制运动功能的神经回路中的作用仅被部分理解。可能需要新的技术来更好地了解脊髓回路的正常功能或部分病变后的可塑性。神经调节是一种主要使用电刺激来重新连接和加强空闲的神经连接的技术，并提供了一些对神经继电器的理解。然而，由于电刺激的性质，它激活了所有的神经元类型，以及在电刺激期间记录神经或肌肉活动的挑战，很难理解不同神经元类型的作用。用光代替电的神经刺激有可能克服这一挑战。神经元的光刺激最初是通过病毒转导的目标细胞群来表达视蛋白以响应光，称为光遗传学。光遗传学已经彻底改变了我们对大脑回路的认识，但由于慢性和自主光传输到这些高度移动区域的技术限制，它的力量尚未在脊髓和周围神经中得到利用。我提出的研究计划旨在克服这些技术差距，并对刺激或沉默目标神经元群的影响有一个基本的了解。我的主要假设是，刺激或抑制特定的神经元类型将使我们了解不同神经元在肌肉活动中的作用。作为材料科学和电子工程的交叉点，我和我的团队将开发工具，使脊髓的光学刺激与无线肌电图（EMG）信号采集相结合。该技术将包括带有不同波长微型发光二极管（µLED）的柔性神经探针，可以放置在动物的脊髓/周围神经上。探针将连接到带有微控制器的印刷电路板（PCB）上，该微控制器被编程为在已经为实现的opsin优化的参数下脉动µled。该PCB连接到无线充电电池，使该设备完全可植入。该系统可以修改为无线可编程，以按需改变光脉动参数。我们还将开发电极和工具来无线获取肌电信号。这些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，我们的系统将提供一个平台，可以同时激发和/或抑制多种类型的神经元，并研究它们在肌肉活动和神经调节中的作用。因此，我们的研究项目将推动加拿大在对大脑以外的神经接力的基本理解方面走在研究的前沿。

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.