Cholinergic basal forebrain neurons as modulators of the cortical microcirculation

Stimulation of the nucleus basalis magnocellularis (NBM) of the basal forebrain, the equivalent of the nucleus basalis of Meynert in primates, induces large increases in blood flow within the cerebral cortex which are mediated by mechanisms involving acetylcholine and nitric oxide. This nucleus provides the majority of the cholinergic input to the neocortex and its degeneration has been associated with dementia of the Alzheimer type. Morphological studies have shown the presence of intimate associations between basalo-cortical fibers and local microvessels, thus providing an anatomic substrate to the functional observations. Furthermore, immunocytochemical investigations coupled to lesion studies have indicated that the vast majority of these neurovascular associations with microarterioles and capillaries, that include the perivascular astrocyte, originate from cholinergic basal forebrain neurons. Other elements such as the intracortical nitric oxide-containing neurons are also innervated by cholinergic neurons from the basal forebrain. These local neurons could serve as intermediaries in the regulation of the cortical microvascular bed by the basal forebrain. Interestingly, the various elements which either compose or are encountered in the environment of the cortical microvessels are endowed with specific receptors for acetylcholine. Although these results suggest that cholinergic basal forebrain neurons could exert a primary role on the intraparenchymal blood vessels either directly or through an intermediary local neuron containing nitric oxide. Such an hypothesis has recently gained support from functional studies which showed no change in oxydative glucose metabolism despite the large increase in cortical perfusion following stimulation of the NBM. These data strongly imply a direct neurogenic effect of the basal forebrain on the intracortical microcirculation and provide the basis for a new mode of regulation of intraparenchymal microarterioles and capillaries by brain neurons, based on neuronal-astroglial-vascular interactions. Further, the contribution of the NBM in the control of cortical vasomotor functions might require a better understanding of its role in microvascular pathology related to either aging or senile dementia of the Alzheimer type.