Optogenetic control of neuronal activity has become a driving force in neuroscience research but its clinical application has been limited due to the fact that delivery of physical light into the brain poses a technical burden. This proposal aims to develop novel optogenetic probes that can report neuronal activity in a non-invasive manner and provide neuromodulation throughout the brain.
This project will develop layers of spatiotemporal control over optogenetic activation by a diffusible chemical (drug) in combination with activity-dependent expression and activation. Neuromodulation will be delivered to neurons autonomously only when and where it is needed. These new reagents will offer two new versatile methods of probing neural circuitry in a noninvasive manner: optically reporting neural activity via bioluminescence and perturbing neural circuitry in a closed-loop fashion. This will be particularly important for conducting long term invivo studies and future clinical translation.