The development of novel imaging tools for real-time detection of molecular neural events, namely neurotransmitter release, is fundamental for studying the basis of brain function and disease. The neurotransmitter acetylcholine is one of the most important modulatory neurotransmitter systems in the brain that plays a critical role in memory, attention, and cognition. The changes in cholinergic activity and related physiological functions, however, have not been fully recognized due to the limitations of current methods to reliably detect the release of neurotransmitters in vivo with sufficient chemical specificity, spatial, and temporal resolution. Recent advances in the development of nanoparticle-based imaging probes and magnetic resonance imaging (MRI) techniques offer the potential to monitor real-time neurotransmitter release in vivo. In this study, we developed a novel MR-active nanosensor to detect acetylcholine, with high level of specificity and sensitivity. The sensing mechanism is based on the hydrolysis of acetylcholine catalyzed by butyrylcholinesterase (BuChE). Acetic acid, one product of the reaction, leads to a drop in local pH which is sensed by pH sensitive contrast agents to alter longitudinal relaxivity (r1), and triggers changes in T1 signal. Calibration curve has shown that r1 of our sensors was enhanced by 30% when concentration of acetylcholine increased from 0 to 10 µM in vitro. Injection of nanosensors to the rat prefrontal cortex proved that our sensors also responded to drug stimulated endogenous release of acetylcholine in vivo.

Nanosensor for chemical imaging of neurotransmitter acetylcholine using MRI

253rd National Meeting (2017)

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