Optical thalamic prosthesis analog for investigating V1 plasticity in blind adult mice

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Project Summary Much research is being done to develop effective neuroprosthetic devices to recover a lost sense. However, even in the case of a prominent success, such as the artificial cochlear implant devices used for recovering hearing, the outcome can be limited when the implantation is done later in life. This is often attributed to the reduced plasticity capacity of the adult brain. This is exacerbated by the fact that even with the best engineering efforts, neuroprosthetic devices are far from providing the rich array of sensory information that is generated by the sensory organs. This is largely due to the limited number of electrode contact points, but also confounded by the difficulties of decoding sensory signals amidst a noisy background. Thus, the neural activity generated by the sensory prosthetic devices are generally distorted and degraded compared to those from intact sensory organs. For the brain to effectively utilize information arising from sensory prosthetic devices, it then becomes essential to rewire the circuitry for optimal processing of the distorted signals. Blindness can result from various causes but usually spares the thalamocortical circuitry, which can be used as a substrate to convey artificial signals from visual prostheses to the cortex. Here we propose to utilize a novel optical thalamic prosthesis analog to examine whether the primary visual cortex (V1) of blind adult mice can be reconfigured to process artificially generated signals. By combining cutting-edge neurophotonic tools, we developed a thalamic visual prosthesis analog by coupling an optical fiber bundle to a GRIN (gradient index) lens implanted in the visual thalamus (dLGN, dorsal lateral geniculate nucleus) of blind adult mice. To activate dLGN neurons using photo-stimulation, we expressed a channelrhodopsin variant in the dLGN neurons. We have preliminary data that neurons in V1 responds to photo-stimulation of discrete dLGN locations. In this proposal, we aim to test whether V1 in blind adult mice express sufficient plasticity to form new representations based on artificial correlations generated from the optical thalamic prosthesis analog. And whether blind adult mice can learn to detect and discriminate such artificial patterns of thalamic activation to guide behavior. Our work can be extended to examine the parameters of the artificial signals generated from the optical thalamic prosthesis analog needed for adult V1 to respond optimally and produce plasticity, as well as determine its usefulness in guiding naturalistic behavior in blind adults. If successful, the results from our work will demonstrate the extent of V1 plasticity and learned behavior that can result from artificial signals, which can benefit future development of effective visual prosthetic devices for recovering vision in blind adults.