Light-activated Tools for Studying Psychoplastogens
- Tombari, Robert
- Advisor(s): Olson, David E
Abstract
Understanding how neuromodulators mediate structural plasticity in the brain is key to treating neuropsychiatric disorders. We discovered a class of molecules known as psychoplastogens that rapidly promote beneficial structural and functional changes in the brain, providing encouragement towards combating these disorders that are challenging to treat. Toward the goal of probing the mechanisms of action of these molecules, I employed a photopharmacological approach that utilized spatial and temporal control of biological systems via activating and deactivating wavelengths of light. My research objective centered around the design, synthesis, and assessment of compounds that photoisomerize with visible light in various biological assays, including in vitro neuroplasticity assays as well as in vivo behavioral assays. By incorporating photoswitchable moieties into various pharmacophores, I identified compounds that exhibit highly enriched trans and cis isomeric ratios when illuminated with discrete wavelengths of light. The isomers differ in geometry and polarity, which affect how the small molecule probes interact with their target receptors, leading to light-dependent biological responses. My library of light-activated psychoplastogens is currently deepening our understanding of this class of molecules and promoting the development of improved versions of these therapeutics.