Linking chemistry to behavior: Long-term optical monitoring of neurotransmission
For over 60 years, drugs that alter, mimic, or block modulatory neurotransmitters have formed the core arsenal for the treatment of neurological disorders such as depression, addiction, schizophrenia, anxiety, and Parkinson’s disease. However, methods to diagnose and validate drug efficacy have remained largely the same: questionnaires and behavioral observations. The archaic nature of neurological disorder diagnosis results from the lack of tools to detect the molecular ‘key players’ of neuronal communication – the three primary modulatory neurotransmitters dopamine, serotonin, and norepinephrine. In this talk, we describe the design, characterization, and implementation of near-infrared optical sensors to image neurotransmitter dopamine. We show direct visualization of endogenous dopamine release over multiple rounds of acute brain slice stimulation, for over 80 minutes. We next introduce a new form of fluorescence microscopy for deep-brain neurotransmitter imaging: double infrared excitation-emission imaging. We characterize our findings in the context of their utility for high spatial and temporal neurotransmitter imaging in the brain, describe nanosensor exciton behavior from a molecular dynamics (MD) perspective, validate nanosensor use in vitro, and for nanosensor use in vivo, to correlate external stimuli (experiences, behavior) to chemical output (neurotransmission).
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.