Near Infrared Nanosensors Enable Optical Imaging of Oxytocin with Selectivity over Vasopressin in Acute Mouse Brain Slices

Oxytocin plays a critical role in regulating social behaviors, yet our understanding of its role in both neurological health and disease remains incomplete. Real-time oxytocin imaging probes with the spatiotemporal resolution relevant to its endogenous signaling are required to fully elucidate oxytocin function in the brain. Herein we describe a near-infrared oxytocin nanosensor (nIROx), a synthetic probe capable of imaging oxytocin in the brain without interference from its structural analogue, vasopressin. nIROx leverages the inherent tissue-transparent fluorescence of single-walled carbon nanotubes (SWCNT) and the molecular recognition capacity of an oxytocin receptor peptide fragment (OXTp) to selectively and reversibly image oxytocin. We employ these nanosensors to monitor electrically stimulated oxytocin release in brain tissue, revealing oxytocin release sites with a median size of 3 m which putatively represents the spatial diffusion of oxytocin from its point of release. These data demonstrate that covalent SWCNT constructs such as nIROx are powerful optical tools that can be leveraged to measure neuropeptide release in brain tissue.