Activating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents.

Multiple areas within the reticular activating system (RAS) can hasten awakening from sleep or light planes of anesthesia. However, stimulation in individual sites has shown limited recovery from deep global suppression of brain activity, such as coma. Here we identify a subset of RAS neurons within the anterior portion of nucleus gigantocellularis (aNGC) capable of producing a high degree of awakening represented by a broad high frequency cortical reactivation associated with organized movements and behavioral reactivity to the environment from two different models of deep pharmacologically-induced coma (PIC): isoflurane (1.25%-1.5%) and induced hypoglycemic coma. Activating aNGC neurons triggered awakening by recruiting cholinergic, noradrenergic, and glutamatergic arousal pathways. In summary, we identify an evolutionarily conserved population of RAS neurons, which broadly restore cerebral cortical activation and motor behavior in rodents through the coordinated activation of multiple arousal-promoting circuits.

Generalized CNS arousal: An elementary force within the vertebrate nervous system.

Why do animals and humans do anything at all? Arousal is the most powerful and essential function of the brain, a continuous function that accounts for the ability of animals and humans to respond to stimuli in the environment by producing muscular responses. Following decades of psychological, neurophysiological and molecular investigations, generalized CNS arousal can now be analyzed using approaches usually applied to physical systems. The concept of "criticality" is a state that illustrates an advantage for arousal systems poised near a phase transition. This property provides speed and sensitivity and facilitates the transition of the system into different brain states, especially as the brain crosses a phase transition from less aroused to more aroused states. In summary, concepts derived from applied mathematics of physical systems will now find their application in this area of neuroscience, the neurobiology of CNS arousal.