(Invited) Long-Term Viability of Optogenetically Transfected Neurons and Implantable Electrodes in the Motor Cortex of Mice

Thursday, 5 October 2017: 15:00
National Harbor 11 (Gaylord National Resort and Convention Center)
C. Gorini (Food and Drug Adminstration), B. Koo (Food and Drug Administration), C. Altimus (Food and Drug Adminstration), and E. Civillico (National Institutes of Health)
Neurological disorders and injuries can result in paralysis and involuntary muscle contractions that interfere with speech, movement and activities of daily living. Current approaches to reduce these dysfunctions, such as selective surgical ablation, oral medications, or electrical stimulation, have important limitations including lack of action or behavioral specificity. There is currently no treatment for spasticity or paralysis that provides targeted, tunable and rapidly reversible control of fine muscle activity. Recently, implantable cortical electrodes have been targeted as a potential therapy for fine control of robotic prosthesis. Implanting these electrodes in the motor cortex has shown promise, however development of long-term systems has yet to be fully understood and the effects of the broad electrical stimulation produced by these devices is still unclear. Optogenetics, a technique that uses light to modulate cells, may provide some relief in producing a stable, long-term intracortical implant with high specificity. Although optogenetic technology has proven to be effective as a research tool and shown promise acutely as a therapeutic intervention in preclinical work, few studies have utilized optogenetics for chronic applications. There is a paucity of knowledge regarding the stability of opsin expression or the neuronal network response to repeated optical stimulation over time. In order to contribute to the understanding of the long-term effects of intracortical devices and optogenetic gene therapy, we performed bilateral injections of an Adeno-associated viral delivery system to transfect the excitatory opsin, channelrhodopsin-2 (ChR2), into the motor cortex of mice. We then unilaterally implanted a 16 channel shank recording optrode into one of the previously injected cortical hemispheres. Following recovery from surgery, spontaneous cortical activity was recorded in freely moving mice. During recording sessions the cortex was illuminated with pulsed 473nm laser light at a variety of frequencies to excite ChR2+ motor neurons. After 8-12 months of weekly recordings, animals were sacrificed and tissue analyzed for changes in microglia response, neuroinflammation, or morphology.