Robert W. Vaughan Lecture in Chemical Engineering

"Neurochemical Probes to Study the Formation of Stable Peer-Relationships"

Neurons communicate through neurochemical 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 neurochemicals, called neuromodulators, and have been the pharmacological targets of antidepressants and antipsychotics for decades. However, until very recently, imaging the spatial and temporal propagation of neurochemical signals was not possible. To this end, we present a library of nanoscale near-infrared fluorescent nanosensors to image synaptic-scale neurochemical propagation of dopamine (Beyene et al. Science Advances 2019; Yang et al. Nature Protocols 2021), serotonin (Jeong et al. Science Advances 2019), and oxytocin (Mun et al. PNAS 2024), and describe how to implement our nanosensors to image neurochemical signaling in living brain tissue. We show that our dopamine probes can uncover synaptic-scale mechanisms of neurochemical signaling aberrations in Huntington's Disease model mice, in which neurons lose their ability to effectively release dopamine. We also show that our oxytocin nanosensors can be used to study non-reproductive peer relationships in voles (Mun et al., PNAS 2025) and find that oxytocin signaling is impaired in voles that show decreased peer relationship preferences (Black et al., Current Biology 2025). We finally discuss the relevance of our findings for supporting advances in understanding and treating neurodegenerative disease, psychiatric conditions, and autism spectrum disorders.