(498a) Invited Speaker: Exciton Engineering for Brain Nanosensor Delivery, and Imaging of Modulatory Neurotransmitters

Neurons communicate through chemical neurotransmitter signals that either terminate at the postsynaptic process (“wired transmission”) or diffuse beyond the synaptic cleft to modulate the activity of larger neuronal networks (“volume transmission”). Molecules such as dopamine belong to the latter class of neurotransmitters, and have been the pharmacological targets of antidepressants and antipsychotics for decades. Owing to the central role of dopamine over a range of behaviors and psychiatric disorders, real-time imaging of the signal’s spatial propagation would constitute a valuable advance in neurochemical imaging. To this end, we present the synthesis and delivery of a nanoscale near-infrared fluorescent nanosensor for dopamine and demonstrate its efficacy for imaging dopamine volume transmission in the extracellular space of the brain striatum and prefrontal cortex with concurrent stochastic simulation validation [1]. The sensor is developed from polymers pinned to the surface of single wall carbon nanotubes (SWNT) in which the surface-adsorbed polymer is the recognition moiety and the carbon nanotube the fluorescence transduction element. Excitonic transitions in functionalized SWNT yield up to ΔF/F = 4500% near-infrared fluorescence emission in the presence of dopamine. We next demonstrate imaging of evoked dopamine release in acute striatal slices, and show disrupted dopamine reuptake kinetics when brain tissue is exposed to antidepressant dopamine reuptake blocker nomifensine. Lastly, we discuss a new form of imaging for deep-brain neuromodulator detection: double infrared excitation-emission fluorescence microscopy [2]. We characterize our findings in the context of their utility for high spatial and temporal neuromodulator imaging in the brain, describe nanosensor exciton behavior from a molecular dynamics (MD) perspective, and validate nanosensor for use in vivo to correlate external stimuli (experiences, behavior) to chemical output (neurotransmission).

References

1. Beyene, A.B., McFarlane, I.R., Pinals, R.L, Landry, M.P.Stochastic Simulation of Dopamine Neuromodulation for Implementation of Fluorescent Neurochemical Probes in the Striatal Extracellular Space. ACS Chemical Neuroscience (2017). DOI: 10.1021/acschemneuro.7b00193

2. Del Bonis O’Donnell, J.T., Page, R.H., Beyene, A.G., Tindall, E.G., McFarlane, I.R., Landry, M.P. Molecular Recognition of Dopamine with Dual Near Infrared Excitation-Emission Two-Photon Microscopy. Advanced Functional Materials (2017). DOI: 10.1002/adfm.201702112