Combining optogenetics and electrical stimulation for precise control of neural modulation

Neuromodulation is widely accepted as a treatment for chronic conditions including severe pain, movement disorders, psychiatric illnesses, as well as restoration of hearing or vision. Electrical pulses are applied to a specific neuronal population to alter their activity, aiming to relieve symptoms or restore function. However, the spread of electrical current can lead to off-target activation with undesired consequences. Clinically, these side-effects can be avoided by limiting the current level or, in the case of the cochlear implant, using interleaved stimulation, but this can come at the expense of reducing the overall efficacy of the treatment. Optogenetics allows highly selective neuromodulation by genetically targeting light-sensitive ion channels to neuronal subpopulations. Furthermore, light can be easily confined to increase the spatial precision of neuromodulation. However, desensitization and heat generation during repetitive stimulation represent significant barriers. Our research program investigates the combination of low-power light and electrical stimulation to reduce the overall levels of light and current in the stimulus, improve the neuronal response reliability compared to optical-only stimulation while maintaining highly targeted activation. Combined (hybrid) optogenetic and electrical stimulation has been explored in the auditory and visual systems for sensory restoration, the peripheral nervous system for chronic pain, and the central nervous system for Parkinson’s disease.