Neurochemical Basis Of Alertness A Norepinephrine

The principal noradrenergic cell groups are found in the locus coeruleus, the lateral tegmentum, and the dorsal medulla. The most important of these for the processes discussed here, being implicated in processes of arousal and attention, are the neurons of the locus coeruleus. These neurons project widely to the fore-brain, including thalamus and hypothalamus, cerebellum, basal forebrain, hippocampus, and throughout the neocortex. They also have descending projections to the sensory nuclei of the brain stem and to the spinal cord. Inputs to the locus coeruleus contrast with these widely distributed outputs because they are restricted to two nuclei of the rostral medulla—the nucleus paragigantocellularis and the nucleus hypoglossi pre-positus. The locus coeruleus does not receive direct sensory input, or indeed any direct input from the forebrain, but rather excitatory sensory input is relayed through these medullary nuclei.

The activity of the locus coeruleus varies with the sleep-wake cycle. The neurons are most active during alert waking and least active during rapid eye movement sleep, even though the cortical EEG shows desynchrony under both of these conditions. Pharmacological stimulation of the locus coeruleus in anesthetized cats results in desynchrony in the EEG.

Neurons of the locus coeruleus respond to sensory input, particularly salient-novel or noxious-environmental stimuli. On the other hand, these neurons are quiet when the subject is awake and behaviorally alert but merely engaged in activities such as grooming or eating. This suggests that the neurons are responding to external stimuli but not to internal stimuli. However, although the neurons respond to salient, unexpected events, the response of the locus coeruleus is not dependent simply on the sensory properties of stimuli but also on their relevance. For example, in vigilance tasks the neurons are responsive to targets but not to nontargets. Furthermore, these neurons show a vigilance decrement, with a decrease in their responsivity over time in the task that corresponds to the behavioral decline in performance. This evidence suggests that locus coeruleus norepinephrine may play a role in vigilance.

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