Neuronal Units Linked to Microvascular Modules in Cerebral Cortex: Response Elements for Imaging the Brain

Abstract

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

“…Our calculations demonstrated that the network behavior is qualitatively independent of d vaso , even though the quantitative results are influenced by its value. In dynamic conditions observed in vivo in rat brains, the magnitude of diameter increases varies from~10% to 45% (Cox et al, 1993;Woolsey et al, 1996;Hillman et al, 2007;Devor et al, 2007;Hutchinson et al, 2006). The maximal value of f vaso (f vaso = 2 corresponding to a 100% vasodilation) used in this study has been overestimated compared to the maximal physiological increase.…”

“…A specific aspect of BOLD contrast where there is continuing controversy on the interpretation of fMRI data is the existence of negative BOLD and its link with neural activity Shmuel et al, 2002;Devor et al, 2007;Northoff et al, 2007;Schridde et al, 2008;Woolsey et al, 1996). In the first paper of this series, Woolsey et al (1996) studied the links between neuronal units and micro-vascular modules in cerebral cortex of the rodent whiskerbarrel system.…”

“…In the first paper of this series, Woolsey et al (1996) studied the links between neuronal units and micro-vascular modules in cerebral cortex of the rodent whiskerbarrel system. They showed that activation that increased flow to particular barrels often led to reduced flow to the adjacent cortex.…”

“…In fact, it is still uncertain whether these changes are sufficiently localized in the actual areas of elevated neuronal activity to resolve submillimeter functional units of the cortex, such as cortical orientation columns ). In addition, emerging spatial patterns such as the vascular steal phenomenon (or surround negativity) Boas et al, 2008;Harel et al, 2002;Woolsey et al, 1996;Cox et al, 1993;Kennerley et al, 2007) will be investigated. …”

Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: Implications for BOLD fMRI

“…Nevertheless, it has been proposed that the change in venous blood volume dominates the total CBV change during altered CBF by neural stimulation and hypercapnia (8,12). However, this assumption is questionable since small arterioles are known to dilate during increased CBF (13)(14)(15).…”