Significance Certain large neurons deep in the brainstem, in the nucleus gigantocellularis (NGC), are crucial for waking up the brain from deep sleep, anesthesia, or injury. NGC neurons, which project axons to central thalamus, should be especially important because central thalamic stimulation heightens CNS arousal in animals and in human patients. We have used the retroTRAP technique to discover mRNAs enriched in such NGC neurons. One mRNA, for endothelial nitric oxide synthase (eNOS), is uniquely expressed. By experiments both on the environmental/sensory side and with respect to motoric regulation, endothelial nitric oxide expression is shown to be functionally important. Five independent lines of evidence indicate that these eNOS neurons have a significant relation with their blood supply.