High-Throughput Evolution of Near-Infrared Oxytocin Nanosensors Enables Oxytocin Imaging in Mice and Prairie Voles

Oxytocin is a neuropeptide thought to play a central role in regulating social and emotional behavior. Current techniques for neuropeptide imaging are generally limited in spatial and temporal resolution, real-time imaging capacity, selectivity for oxytocin over vasopressin, and application in young and non-model organisms. To avoid the use of endogenous oxytocin receptors for oxytocin probe development, we employed a protocol to evolve purely synthetic molecular recognition on the surface of near-infrared fluorescent single-walled carbon nanotubes using single-stranded DNA . This probe reversibly undergoes up to a 172% fluorescence increase in response to oxytocin with a Kd of 4.93 µM. Furthermore, this probe responds selectively to oxytocin over oxytocin analogs, receptor agonists and antagonists, and most other neurochemicals. Lastly, we show our probe can image synaptic evoked oxytocin release in live mouse and prairie vole brain slices. Optical probes with the specificity and resolution requisite to image endogenous oxytocin signaling that are readily applicable in different animal model species can advance the study of oxytocin neurotransmission for its role in both health and disease.