UC Berkeley

In order to fully characterize complex biological systems such as neural circuits, rapid and accurate mapping of cellular membrane potentials is highly desired. Voltage sensitive dyes offer a highly advantageous solution to this problem through inserting into cellular membranes and displaying changes in fluorescence quantum yield in response to changes in membrane potential. One class of voltage sensitive dyes, VoltageFluors (VF dyes), use a photoinduced electron transfer (PeT) mechanism to sense changes in membrane potential. These dyes consist of an electron-rich aniline donor group, a conjugated molecular wire, and a fluorophore acceptor group. In this dissertation, we examine various derivatives of VF dyes to investigate how modifications to the aniline donor and molecular wire regions affect the voltage sensitivities and signal-to-noise ratios of VF dyes. We also incorporate sulfone rhodamine chromophores into the VF Dye scaffold in order to generate voltage sensitive dyes which absorb and emit above 700 nm. Finally, we apply VF Dyes to dissociated neurons to optically investigate differences in neuronal excitability and connectivity at different stages of development and in different disease models.