A Combination Optical and Electrical Nerve Cuff for Rat Peripheral Nerve

Abstract

Spinal cord injury results in life-long damage to sensory and motor functions. Recovery from these injuries is limited and often insufficient because the lack of stimulation from supraspinal systems results in further atrophy of the damaged neural pathways. Current studies have shown that repeated sensory activity obtained by applying stimulation enhances plasticity of neural circuits, and in turn increases the ability to create new pathways able to compensate for the damaged neurons. Functional electrical stimulation has been proven to show success in this form of rehabilitation, but it has its limitations. Stimulating neural pathways with electricity results in also stimulating surrounding neurons and muscle tissue. This results in attenuation of the intended effect. The use of optogenetics mitigates this issue, but comes with its own complications. Optogenetics is a growing method of neural stimulation which utilizes genetic modification to create light activated ion channels in neurons to allow for activation or suppression of neural pathways. In order to activate the neurons, light of the appropriate wavelength must be able to penetrate the nerves. Applying the light transcutaneously is insufficient, as the skin and muscle tissue attenuate the signal. The target nerve may also move relative to an external point on the body, creating further inconsistency. Specifically in the case of using a rat model, an external object will be immediately removed by the animal. This thesis seeks to address this issue for a rat model by designing a nerve cuff capable of both optical and electrical stimulation. This device will be scaled to fit the sciatic nerve of a rat and allow for both optical activation and inhibition of the neural activity. It will be wired such that each stimulus may be operated individually or in conjunction with each other. The simultaneous stimulation is required in order to validate the neural inhibition facet. The circuit itself will be validated through the use of an optical stimulation rig, using a photoreceptor in place of an EMG. The application of the cuff will be verified in a live naive rat. Aim 1: Design and build an implantable electrical stimulation nerve cuff for the sciatic nerve of rats. An electrical nerve cuff for the sciatic nerve of a rat will be designed and assembled such that it is able to reliably activate the H-reflex. For it to be used in a walking rat, the cuff must be compatible with a head mount in order to prevent the rat from being able to chew at the wiring or their exit point. The cuff will be controlled through a Matlab program that is able to output specified signals and compare these outputs directly with the resultant EMG inputs. Aim 2: Implement LEDs onto the cuff and perform validation experiments. Light delivery capability will be added to the cuff through the use of LEDs. The functionality of the cuff will be validated through tests on naive rats. If successful, only an electric stimulation will result in a muscle twitch. An optical stimulation should result in no twitches, which would then validate that no current is leaking from the nerve cuff, given that the rat does not express any light sensitive protein channels. Ultimately, with a rat expressing ChR2 opsins on the sciatic nerve, an activation of the nerve using a blue light of wavelength 470nm will result in activating an h-wave without an m-wave when optically stimulated. Similarly, using the nerve cuff with a rat expressing ArchT opsins will result in suppressing the h-wave from an electric stimulation once the sciatic nerve is illuminated with green light of a wavelength of 520 nm.