Optical stimulation for restoration of motor function after spinal cord injury

Abstract

Spinal cord injury can be defined as a loss of communication between the brain and the body due to disrupted pathways within the spinal cord. Although many promising molecular strategies have emerged to reduce secondary injury and promote axonal regrowth, there is still no effective cure, and recovery of function remains limited. Functional electrical stimulation (FES) represents a strategy developed to restore motor function without the need for regenerating severed spinal pathways. Despite its technological success, however, FES has not been widely integrated into the lives of spinal cord injury survivors. In this review, we briefly discuss the limitations of existing FES technologies. Additionally, we discuss how optogenetics, a rapidly evolving technique used primarily to investigate select neuronal populations within the brain, may eventually be used to replace FES as a form of therapy for functional restoration after spinal cord injury.

Figure 1. Mechanisms of neuromodulation via optogenetics

A) Application of blue light (470 nm wavelength) leads to a conformational change of the trans membrane ion channel protein, channelrhodopsin, allowing a flow of positively charged ions into the cytoplasm, ultimately leading to neuron depolarization. B) Yellow light application (580 nm wavelength) changes the conformation of the trans membrane ion pump protein, halorhodopsin, allowing negatively charged ions to move into the cytoplasm, leading to neuron hyperpolarization. C) Schematic comparing the non-specific activation characteristic of electrical activation, leading to both desired and undesired effects, and optical activation of only targeted neurons, leading to only desired effects. Ca²⁺ = calcium ion; ChR-2 = channelrhodopsin; Cl^- = chloride ion; H⁺ = hydrogen ion; HR = halorhodopsin; K⁺ = potassium ion; Na⁺ = sodium ion Adapted with permission from Macmillan Publishers Ltd: [Nature Reviews Neuroscience], copyright 2007.

Figure 2. Fatigue resistance comparison between optical and electrical stimulation

A) Average tetanic muscle tension during 2 min stimulation with 250 ms trains of stimulation at 1 Hz using electrical and optical stimulation (n=7, shaded region is standard error of the mean, average body weight = 0.258 ± 0.01 N). B) Average fatigue index measured as decline in tetanic muscle tension over 2 min (n=7). C) Tetanic tension from a single mouse during optical and electrical stimulation in the hind limbs over 20 minutes. BW = average body weight Adapted with permission from Macmillan Publishers Ltd: [Nature Medicine], copyright 2010.