Technological advances for the neuromodulation of the spinal cord

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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.