In situ Electrochemical Generation of Nitric Oxide for Neuronal Modulation

Understanding the function of nitric oxide (NO), a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule in situ to specific cells. To address this need, we developed iron sulfide nanoclusters that catalyse NO generation from benign sodium nitrite in the presence of modest electric fields. Locally generated NO activates the NO-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and latency of TRPV1-mediated Ca(2+) responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows NO-mediated neuronal interrogation in vivo. In situ generation of NO within the ventral tegmental area via the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This NO generation platform may advance mechanistic studies of the role of NO in the nervous system and other organs.