Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of sensory alertness, mobility and readiness to respond. There are many different neural systems involved in what is collectively known as the arousal system. Five major systems originating in the brainstem, with connections extending throughout the cortex, are based on the brain’s neurotransmitters, acetylcholine, norepinephrine, dopamine, histamine, and serotonin. When these systems are stimulated, they produce cortical activity and alertness. The Noradrenergic system is a bundle of axons that originate in the locus coeruleus and ascends up into the neocortex, limbic system, and basal forebrain. Most of the neurons are projected to the posterior cortex which is important with sensory information, and alertness. The activation of the locus coeruleus and release of norepinephrine causes wakefulness and increases vigilance. The neurons that project into the basal forebrain impact cholinergic neurons that results in a flood of acetylcholine into the cerebral cortex. The Acetylcholinergic system has its neurons located in the pons and in the basal forebrain. Stimulation of these neurons result in cortical activity, shown from EEG records, and alertness. All of the other four neurotransmitters play a role in activating the acetylcholine neurons. Another arousal system is the dopaminergic system which releases dopamine that is produced by the substantia nigra. The neurons arise in the ventral tegmental area in the midbrain, and projects to the nucleus accumbens, the striatum forebrain, limbic system, and prefrontal cortex. The limbic system is important for control of mood and the nucleus accumbens signal excitement and arousal. The path terminating in the prefrontal cortex is important in regulating motor movements, especially reward oriented movements. The Serotonergic system which has almost all of its serotonergic neurons originating in the raphe nuclei. This system projects to the limbic system as well as the prefrontal cortex. Stimulation of these axons and release of serotonin causes cortical arousal and impacts locomotion as well as mood. The last system is the histamergenic system. The neurons are located in the tuberomammillary nucleus of the hypothalamus. These neurons send pathways to the cerebral cortex, thalamus, and the basal forebrain, where is stimulate the release of acetylcholine into the cerebral cortex. All of these systems are very much linked and show similar redundancy. These pathways I’ve described are all ascending pathways, but there also arousal pathways that descend. One example is the Ventrolateral Preoptic area which release GABA inhibitors, which interrupt wakefulness and arousal. Neurotransmitters of the Arousal system such as Acetylcholine and norepinephrine work to inhibit the Ventrolateral preoptic area.