(Invited) Nanoscale Insights into Dopamine Release: Single-Strand DNA Functionalized SWCNTs in Neuroscience

Single-stranded DNA (ssDNA)-functionalized single-wall carbon nanotubes (SWCNTs) exhibit exceptional optical sensitivity to catecholamines, including dopamine and norepinephrine—key signaling molecules that play vital roles in brain function. This unique capability positions SWCNTs as powerful tools for advancing our understanding of neurochemical processes involving dopaminergic and noradrenergic neurons. In this presentation, I will highlight how our lab has leveraged SWCNT nanosensors to push the boundaries of dopamine neuroscience. For studies in cultured neurons, we developed a composite nanofilm strategy that enabled us to visualize dopamine release with exceptional resolution, capturing single bouton activity with quantal sensitivity while monitoring thousands of release sites simultaneously in large imaging fields of view. By combining SWCNT-based activity imaging with immunofluorescence, electron microscopy, and cutting-edge molecular, cellular and genetic techniques, we have gained new insights into neurobiological properties of dopamine release sites in dopaminergic neurons that had heretofore been inaccessible with conventional methods of inquiry. Building on these advances, I will discuss recent progress in the development of in vivo-compatible dopamine nanosensors. These innovations have allowed us to monitor dopamine dynamics in awake and behaving mice, bridging the gap between molecular-scale imaging and real-time behavior analysis. Furthermore, I will discuss methodological developments that enabled the deployment of these nanosensors in vivo. Looking ahead, these SWCNT-enabled technological advancements hold potential for the study of neurochemical signaling, offering deeper insights into both normal brain function and the pathophysiology of disorders involving catecholamines. Future work aims to expand the applications of these nanosensors to other neural circuits and neuromodulators, ultimately advancing our ability to decode the brain’s chemical language.