A micro-LED implant and technique for optogenetic stimulation of the rat spinal cord.

To date, relatively few studies have used optogenetic stimulation to address basic science and therapeutic questions within the spinal cord. Even less have reported optogenetic stimulation in the rat spinal cord. This is likely due to a lack of accessible optogenetic implants. The development of a device that can be fabricated and operated by most laboratories, requiring no special equipment, would allow investigators to begin dissecting the functions of specific neuronal cell-types and circuitry within the spinal cord, as well as investigate therapies for spinal ailments like spinal cord injury. Here, we describe a long-term implantable µLED device designed for optogenetic stimulation of the spinal cord in awake, freely moving rats that is simple enough to be fabricated, implanted and operated by most laboratories. This device, which sits above the dorsal cord, can induce robust movements for at least 6 weeks without causing physical or thermal damage to the underlying spinal cord. In this regard, the presented µLED device could help tease apart the complexities of the spinal cord and uncover potential future therapeutics.

Optogenetic surface stimulation of the rat cervical spinal cord.

Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. Here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats, adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.

Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury.

OBJECTIVE: Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. APPROACH: We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. MAIN RESULTS: Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. SIGNIFICANCE: The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

NeuroGame Therapy to improve wrist control in children with cerebral palsy: a case series.

OBJECTIVE: This case series examines the feasibility, specificity, and preliminary effectiveness of NeuroGame Therapy (NGT) for improving wrist control in four children with cerebral palsy (CP). NGT uses surface electromyographic (sEMG) signals routed through motivating computer games to improve motor control. METHODS: Primary outcomes of NGT included feasibility (hours of play) and specificity (changes in sEMG activity during game play). Secondary outcomes included changes in co-contraction, range of motion, segmental alignment, and spontaneous upper extremity function following intervention. RESULTS: Participants completed a mean of 8.8 hours of NGT over 5-6 weeks. Participants demonstrated dramatic improvement of the sEMG activity during game play. Several participants also showed improvements in range of motion, co-contraction, and spontaneous upper extremity function following NGT. CONCLUSION: This case series provides evidence for the feasibility, specificity, and effectiveness of NGT. Future studies will pair NGT with functional practice to improve transfer of learning to daily activities.