Neuronal activity within the brain evokes local increases in blood flow, a response termed functional hyperemia. This response ensures that active neurons receive sufficient oxygen and nutrients to maintain tissue function and health. In this review, we discuss the functions of functional hyperemia, the types of vessels that generate the response, and the signaling mechanisms that mediate neurovascular coupling, the communication between neurons and blood vessels. Neurovascular coupling signaling is mediated primarily by the vasoactive metabolites of arachidonic acid (AA), by nitric oxide, and by K + . While much is known about these pathways, many contentious issues remain. We highlight two controversies, the role of glial cell Ca 2+ signaling in mediating neurovascular coupling and the importance of capillaries in generating functional hyperemia. We propose signaling pathways that resolve these controversies. In this scheme, capillary dilations are generated by Ca 2+ increases in astrocyte endfeet, leading to production of AA metabolites. In contrast, arteriole dilations are generated by Ca 2+ increases in neurons, resulting in production of nitric oxide and AA metabolites. Arachidonic acid from neurons also diffuses into astrocyte endfeet where it is converted into additional vasoactive metabolites. While this scheme resolves several discrepancies in the field, many unresolved challenges remain and are discussed in the final section of the review.
Bibliographical noteFunding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported by NIH grants R01-EY004077, EY026514, and EY026882 to EAN; MinnCReST Predoctoral Training Fellowship T90 DE 022732; and the NIH Predoctoral Training of Neuroscientists Grant T32GMOD8471.
- arachidonic acid
- cerebral blood flow
- functional hyperemia
- neurovascular coupling