Arterial dilation in the parenchyma of the cerebral cortex in response to stimulation of the nucleus basalis of Meynert measured by two-photon microscopy

Histological studies have shown that fiber terminals from basal forebrain cholinergic areas (e.g., nucleus basalis of Meynert, NBM) have intimate contact not only with neurons, but also with parenchymal blood vessels, such as penetrating arteries, in the cerebral cortex. Stimulation of the NBM produces an increase in cortical blood flow, by activating muscarinic and nicotinic cholinergic receptors, without changing cortical glucose metabolism. Therefore, it has been hypothesized that cholinergic projection from the NBM has a vasodilator function. In this study, we used two-photon microscopy to directly observe response of cortical parenchymal arteries to the NBM stimulation. Imaging of cortical vasculature was performed by two-photon microscopy in mice anesthetized with urethane and artificially ventilated. The diameter of single penetrating arteries of the frontal cortex was measured at different depths (~800 μm, layers I-V) and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30-50 μA and 50 Hz) and hypercapnia (3% CO2 inhalation). At the resting condition, the diameters of penetrating arteries measured ranged 10 - 28 μm. Stimulation of the NBM caused the diameter of penetrating arteries to increase by 9 - 13% of the pre-stimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 sec after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM.