Imaging Neuromodulation in the Brain with Near-Infrared Fluorescent Nanosensors
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, serotonin, and neuropeptides such as oxytocin 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 neuromodulators such as 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 a library of nanoscale near-infrared fluorescent nanosensors for dopamine, serotonin, and oxytocin, where the nanosensors are 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 (Beyene et al. Nano Letters 2018), ΔF/F = 200% for serotonin (Jeong et al. Science Advances 2019), and ΔF/F = 120% for oxytocin (unpublished). We next demonstrate imaging of evoked dopamine release in acute striatal slices, and show altered dopamine reuptake kinetics when brain tissue is exposed to dopamine receptor agonist and antagonist drugs (Beyene et al. Science Advances 2019). We characterize our findings in the context of their utility for high spatial and temporal neuromodulator imaging in the brain to study Huntington’s Disease and discuss generalizable approaches to generation of nanosensors for other neurotransmitters, neuromodulators, and neuropeptides.