Fig. 2.

Signalling pathways mediating neurovascular coupling. When neurons are active they release glutamate which generates action potentials in interneurons containing NOS and activates metabotropic glutamate receptors (mGluR) in astrocytes. As a result [Ca²⁺]_i rises in both cell types, releasing NO and derivatives of arachidonic acid to dilate local arterioles and increase blood flow. In addition arachidonic acid diffuses to arterioles and is converted into 20-HETE which constricts the vessels. K⁺ release from astrocytes via large conductance Ca²⁺-activated K⁺ channels (BK_Ca channels) may also dilate vessels by promoting K⁺ efflux through smooth muscle inward rectifier K⁺ channels (K_ir) and thus generating hyperpolarization. Blood flow changes evoked by release of adenosine, lactate and interneuron peptide transmitters are not shown on this diagram. Vasodilation occurs in the context of constriction of arterioles produced by the amine transmitters noradrenaline, dopamine and 5-HT. Noradrenaline evokes constriction by acting on α-adrenergic receptors on arteriole smooth muscle and on astrocytes. Developmental changes in any of the components will alter the BOLD response.