Neuronal messengers as mediators of microvascular tone in the cerebral cortex

Abstract

Changes in regional neuronal activity are accompanied by concurrent temporal and spatial changes in the cerebral blood flow and these form the basis of modern brain imaging techniques used to map the functional neuronal activity. This neurovascular coupling is achieved by several mechanisms that are still poorly understood but ionic, glial, metabolic, and neuronal factors have been involved. In the present investigation, we provide evidence that specific populations of cortical interneurons, which play a central role in integrating multiple incoming local and afferent synaptic and paracrine signals, could act as local integrators of the neuronal activity and cerebral blood flow. We suggest that different subpopulations of cortical γ-amino-butyric acid (GABA) interneurons, which colocalize specific vasoactive substances such as nitric oxide (NO), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY), could serve as a functional relay in the neurovascular coupling that accompanies the activation of basal forebrain acetylcholine (ACh) and brainstem raphe nucleus serotonin (5-HT)-neurons. Thus, in addition to direct changes in the microvascular tone induced by ACh and 5-HT fibers projecting to cortical microvessels, these neurons also send projections to NO, VIP and/or NPY interneurons which, via their direct neurovascular projections, could affect the microvascular tone and therein adapt changes in perfusion to the local changes in neuronal activity. The results suggest that specific populations of GABA interneurons constitute a functional unit with their respective neuronal and vascular effects.