Advisory Committee Chair
Gary M Gray
Advisory Committee Members
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Optogenetics is a growing discipline of neuroscience that attempts to control brain circuits using light. Current techniques involving surgically implanted light-emittingdiodes are highly invasive. This limitation could be avoided by the use of a tissuepenetrative light source, such as x-rays, and a locally applied down-converting material. This work describes the design, optimization, and proof-of-concept application of organic aromatic-based scintillators as non-invasive tools for optogenetics. The first chapter describes the synthesis of 2-anthryl methacrylate-co-methyl methacrylate copolymers and an evaluation of their use as x-ray induced scintillators (radioluminescence). The 2-anthryl methacrylate monomer and the copolymers all exhibited radioluminescence in the solid state. The crystalline monomer had the greatest radioluminescent output of the new materials but was only 25% as intense as pure anthracene. This was not sufficiently intense to generate a synaptic response from neurons containing bacterial rhodopsin. However, the UV-induced fluorescence of these materials is much stronger. This allowed them to be used in a proof-of-concept experiment to determine if down-conversion carried enough intensity to drive a synaptic response. Increased synaptic activity was observed in hippocampal slices containing neurons expressing an optogenetic target when locally applied anthracene-copolymers fluoresced under UV-irradiation. The second chapter details the optimization of crystalline aromatic organic scintillators through phosphonate ester functionalization. A series of phosphonate esters with varying substituents (“heavy” atoms and aromaticity) were studied to determine how those substituents affected the optical and radioluminescence properties. All the compounds exhibited radioluminescence in the solid-state. Five of the anthracenephosphonates also showed stronger radioluminescence than pure anthracene; in some cases an increase in emission intensity of over 200% was seen. Solid-state structures highlighted the importance of aromatic interactions in the radioluminescence mechanism. The final chapter explores the development of into water-soluble organic scintillators for use in optogenetics. Water-soluble arylphosphonate salts were prepared by the hydrolysis of phosphonate-esters. These salts all exhibited micelle formation, and fluorescence characterization indicate intermolecular interactions in the micelle core. Quantifiable radioluminescence of a salt solution was observed and was attributed to micelle formation. The emission of this salt perfectly matches an optogenetic target and could be a powerful tool in non-invasive optogenetics.
French, David, "Functionalized Aromatic Organic Scintillators As Tools For Non-Invasive Optogenetics" (2020). All ETDs from UAB. 1669.