One or many arousal systems? Reflections on some of Giuseppe Moruzzi's foresights and insights about the intrinsic regulation of brain activity.

Soon after the birth of the hypothesis of the ascending brainstem activating system, Giuseppe Moruzzi considered the possibility that a fractionated and differentiated arousing action of the reticular formation is required for effective behavior and cognition. Current knowledge about the chemically tagged brainstem systems which project diffusely to thalamus, neocortex and limbic structures has justified the assumption of the existence of multiple arousal systems. Combined changes in the activities of these systems are responsible for the sleep-wake cycle and the modulation of the reactivity of the brain to environmental inputs. There remains the physiological problem--one which has always been foremost in Moruzzi's thinking about the intrinsic regulation of brain activity--of how the separate actions of the different arousal systems are brought together into a functional whole. This problem still awaits experimental answers.