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In the rat, activation of the intracerebral cholinergic system originating in the basal forebrain and projecting to the cortex and hippocampus releases acetylcholine in the cortex and hippocampus, which results in vasodilation and an increase in regional cerebral blood flow (rCBF) in the cortex and hippocampus. The augmentation of rCBF is independent of both systemic blood pressure and regional metabolism. The intracerebral cholinergic fibers are able to act as autonomic nerve fibers for the regulation of cortical and hippocampal blood flow. [Copyright &y& Elsevier]

This article reviews the study of neural vasodilator mechanisms of the cerebral cortex by basal forebrain cholinergic nerve fibers and their age-related function in rats. During the last decade, we have demonstrated a neural regulatory system of cerebral blood flow in rats involving intracerebral cholinergic vasodilator nerve fibers originating in the basal forebrain and projecting to the cerebral cortex. Activation of these cholinergic vasodilator fibers results in the release of acetylcholine (ACh) within the cortex, activation of both nicotinic and muscarinic ACh receptors, and vasodilatation without coupling to glucose metabolic rates. This cholinergic vasodilator system has been shown to decline with age in rats mainly due to age-related declines of nicotinic ACh receptor activity. However, muscarinic ACh receptor activity and the release of ACh into the extracellular space in the cortex are well maintained during aging. The present age-related decline of the intracerebral cholinergic vasodilator system found in rats seems to affect cognitive function during aging, although this cholinergic vasodilator system has not yet been demonstrated in humans. [Copyright &y& Elsevier]