Modulation of cortical activation and the anatomy of the reticular activating system

Specific information to the cerebral cortex, for example relating to sensory stimuli in the periphery, is relayed via the main thalamic nuclei. The other, diffusely projecting, systems are most likely to be involved in the regulation of cortical responsivity. Such a role has been demonstrated electrophysiologically for the claustrum, and the pharmacology of the antihistamines indicates a role for this transmitter system in the regulation of cortical arousal. The cholinergic input from the basal forebrain is necessary for the proper functioning of the cortex, and its degeneration is associated with cognitive decline and memory impairment. The possible relationship of mesolimbic dopamine pathways to schizophrenia is well known. Similarly, the psychopharmacology of serotonin also implies a major role for this transmitter system in the proper functioning of the cortex. There are two routes by which these 'non-specific' pathways affect the cortex: direct projections, and an indirect pathway through the thalamus. Brainstem nuclei send fibres to the intralaminar and midline nuclei, which in turn send fibres to the entire cortex including the hippocampus. The cholinergic input from the interpeduncular nucleus to the intralaminar nuclei is prominent. Serotonin is particularly concentrated in the midline nuclei. There are other reticular formation projections to these nuclei, but the transmitters remain uncertain. This latter indirect route by which the reticular formation of the brainstem impinges on the cerebral cortex via the thalamus constitutes the reticular activating system. The role of this system in cortical arousal is well documented.

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