A computational model relating changes in cerebral blood volume to synaptic activity in neurons

Brain imaging methods, and in particular fMRI (functional Magnetic Resonance Imaging), do not detect neural activity directly, but rather changes in blood flow and oxygenation in neighboring blood vessels, this being the BOLD (Blood Oxygenation Level Dependent) effect. We have constructed a model of the steps leading from neural activity to increased blood flow in arterioles, in which astrocytes play a crucial role. Glutamate released from neuronal synapses binds to metabotropic receptors on the astrocyte processes that ensheath these synapses. This initiates a calcium wave that travels along the endfeet of astrocytes that abut the endothelial cells forming the walls of blood capillaries; this calcium wave is propagated by the extracellular diffusion of ATP (adenosine triphosphate) that acts on metabotropic purinergic receptors on the astrocytes. A further second messenger (taken to be nitric oxide) relays this signal to the smooth muscle cells forming the outer walls of arterioles, and the subsequent wave of hyperpolarization reduces calcium influx and allows relaxation of the muscle cells and hence increased blood flow. The model gives results that are in agreement with experimental measurements of blood volume changes in the arterioles in the visual cortex of optically stimulated cats.