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.
Optogenetics has been demonstrated to stimulate specific types of neurons at millisecond resolution. However it requires the application of both implanted optical fiber and virus, which limit its clinical application. The goal of this proposed project is to develop a cell-specific neural stimulation method without the application of optical fiber and viruses. This success of this project could result in a non-invasive method for treating brain disease such as Parkinson's disease and depression.
| Rivnay, Jonathan; Wang, Huiliang; Fenno, Lief et al. (2017) Next-generation probes, particles, and proteins for neural interfacing. Sci Adv 3:e1601649 |
