Nitric oxide signaling in the brain: translation of dynamics into respiration control and neurovascular coupling.

The understanding of the unorthodox actions of neuronal-derived nitric oxide ((•)NO) in the brain has been constrained by uncertainties regarding its quantitative profile of change in time and space. As a diffusible intercellular messenger, conveying information associated with its concentration dynamics, both the synthesis via glutamate stimulus and inactivation pathways determine the profile of (•)NO concentration change. In vivo studies, encompassing the real-time measurement of (•)NO concentration dynamics have allowed us to gain quantitative insights into the mechanisms inherent to (•)NO-mediated signaling pathways. It has been of particular interest to study the diffusion properties and half-life, the interplay between (•)NO and O(2) and the ensuing functional consequences for regulation of O(2) consumption, the role of vasculature in shaping (•)NO signals in vivo, and the mechanisms that are responsible for (•)NO to achieve the coupling between glutamatergic neuronal activation and local microcirculation.