| Description: |
In this dissertation, I present novel optical tools for studying the uptake and release of serotonin in living brain tissue. These optical tools include small molecules that act as either substrates or antagonists of the serotonin transporter (SERT) and genetically encoded biosensors that work orthogonally to these small molecules to detect the release of endogenous serotonin in living brain tissue. Together, these optical methods comprise an imaging platform to study the uptake and release of serotonin in living brain tissue. One small molecule, SERTlight, has been employed to characterize the synaptic reuptake inhibitor (SynRI) properties of 12-methoxyibogamine (ibogaine) and its metabolites. Both in isolation and in complex with one another, these tools constitute new techniques for studying the uptake and release of serotonin in living brain tissue with improved spatial resolution, temporal resolution, and ease of use compared to previously established methods. It is the sincere hope of the Sames and Sulzer Laboratories that these tools will enable and inspire future generations of neuroscientists to study the serotonin system at synaptic resolution with the goal to better understand serotonin action in both normal and diseased states. |