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

Abstract

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 μm 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.

Identifying Neural Signatures of Dopamine Signaling with Machine Learning

“…Beyond this study, many datasets exist in the literature and could readily benefit from machine learning and feature mining approaches. This includes analyses of neuronal activity and neurochemical signaling data from the growing number of neurotransmitter, neuromodulator, and neuropeptide optical probes. ,,− Machine learning-based analysis of neurochemical imaging datasets could provide a user-independent approach to analyzing neurochemical imaging features and implementing those analyses to advance neurobiology research.…”

Carbon Nanomaterial Fluorescent Probes and Their Biological Applications

“…A recent report has expanded the use of SWCNT-based neurochemical sensing from small molecules to neuropeptides by employing a rational approach for sensor synthesis . This approach eschews the low throughput and tedious screening strategies that are used to identify molecular recognition motifs for target analytes, and instead uses a rational design strategy for developing a sensor for a neuromodulator called oxytocin.…”

“…In the mammalian brain, oxytocin plays an evolutionarily conserved role in regulating important aspects of social behavior, particularly in establishing and maintaining social bonds, and regulating maternal care. In the study, an oxytocin receptor peptide fragment is used as the molecular recognition motif, where it is covalently linked to the surface of SWCNT . The covalently functionalized SWCNT scaffold is further passivated and solubilized noncovalently with ssDNA.…”

“…In the study, an oxytocin receptor peptide fragment is used as the molecular recognition motif, where it is covalently linked to the surface of SWCNT. 1089 The covalently functionalized SWCNT scaffold is further passivated and solubilized noncovalently with ssDNA. The hybrid covalent and noncovalent approach offers a unique strategy that scaffolds the nanotube surface with the molecular recognition and solubilizing motifs serially.…”

“…Although important as conceptual advances, the broader applicability of both approaches remains to be seen A recent report has expanded the use of SWCNT-based neurochemical sensing from small molecules to neuropeptides by employing a rational approach for sensor synthesis. 1089 This approach eschews the low throughput and tedious screening strategies that are used to identify molecular recognition motifs for target analytes, and instead uses a rational design strategy for developing a sensor for a neuromodulator called oxytocin. Oxytocin is an important neuropeptidergic hormone that is released from a small cluster of neurons.…”