Targeted, wireless neural stimulation with near-infrared light absorbing carbon nanotubes

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Project Summary Optogenetics is a technique that was developed around 10 years ago to genetically modify specific types of neurons with light-sensitive proteins, and hence enabling the control of these neurons with light in millisecond temporal resolution. However, there are two major disadvantages with optogenetics: (1) Expression of light- sensitive proteins in specific neurons would require virus transduction, which would take at least several weeks for expression and might cause safety issues in clinical applications. (2) Implantation of a rigid optical fiber in the brain is invasive and has been shown to produce glial action and lesions, which are not desirable for both research and clinical applications. Here, I would to propose a method to wirelessly stimulate specific neuron types in without the application of both virus and optical fiber. The approach will be using carbon nanotubes as a near-infrared light absorber and heat generator for neuron stimulation. Since near-infrared light can penetrate deeply in skull and brain tissues, the stimulation can be done wirelessly by using a near-infrared source outside of the skull. The targeting of specific neurons by carbon nanotubes will be achieved by functionalizing carbon nanotubes with antibodies or peptides. In Specific Aim 1, I will tune the carbon nanotube functional groups, concentrations and incubation times to achieve low-power near-infrared light stimulation of neurons activity in vitro. In Specific Aim 2, I will apply various antibodies and antibody conjugation methods with carbon nanotubes for targeting specific cell receptor/channels in vitro. In Specific Aim 3, I will target antibody functionalized carbon nanotubes to specific neurons receptors in vivo and stimulate the targeted neurons with near-infrared light source outside of the mice skull. The outcome of this proposed work will be a wireless, non-viral method for stimulation of specific neurons in a freely behaving animal.