Regulation of cerebral cortical blood flow by the basal forebrain cholinergic fibers and aging

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.