Title: Chemical Targeting of Voltage Sensitive Dyes in the Brain
Description: Voltage sensitive dyes are a family of chemical sensors which enable optical recording of electrical activities from large populations of neurons, but nevertheless suffer from the lack of delivery and targeting strategies in brain tissue due to their generally high lipophilicity. In this dissertation, I present a purely chemical approach to target voltage sensitive dyes to natively expressed protein targets in live brain tissue and achieve functional voltage imaging with the limited photon budget afforded by the small number of sensors targeted to endogenous molecular targets. To our knowledge, this study represents the first example of functional optical recording from specific neuronal types and their axons in live brain tissue without any genetic manipulation. Such approach is vastly significant in the long run when we ultimately need to translate findings from model animals in research laboratories to benefit real human patients in clinical settings, to which imaging and diagnostic methods requiring genetic modification are and will remain problematic in the foreseeable future.

In addition, we demonstrate the high modularity and versatility of our chemical approach in targeting different voltage sensitive dyes to various molecular targets in the brain. We believe that the same concept can be applied to the targeting and delivery of other important lipophilic cargos, such as drugs and other sensors, to enable genetic modification-free, cell- or molecule-specific imaging and pharmacology in the brain.