Fig. 12.

Summary of signaling pathways that mediate neurovascular coupling in the central nervous system. Synaptically released glutamate acts on NMDA receptors in neurons (NMDAR) to raise [Ca²⁺]_i, causing neuronal nitric oxide synthase (nNOS) to release NO, which activates smooth muscle guanylate cyclase. Raised [Ca²⁺]_i may also (dashed line) generate arachidonic acid (AA) from phospholipase A₂ (PLA₂), which is converted to prostaglandins (PG) that dilate vessels. Glutamate also raises [Ca²⁺]_i in astrocytes by activating metabotropic glutamate receptors (mGluR), generating arachidonic acid and three types of AA metabolites: prostaglandins and EETs in astrocytes, which dilate vessels, and 20-HETE in smooth muscle, which constricts vessels. A rise of [Ca²⁺]_i in astrocyte endfeet may also activate Ca²⁺-gated K⁺ channels (gK(Ca); alternative abbreviation: BK), releasing K⁺, which also dilates vessels. In the retina, Müller glial cells are activated by ATP rather than glutamate released from neurons. Calcium increases in Müller cells result in the release PG and EETs onto smooth muscle cells, which dilate vessels, and 20-HETE production, which constricts vessels; from Attwell et al. (2010).