Glial laminar cortical architecture matches metabolic demand.

The link between increased neural activity and cerebral blood flow is well established (Roy and Sherrington, 1890); yet, the mechanism by which blood flow is matched to neuronal activity both spatially and temporally is unclear. Based on their morphology, gray matter (protoplasmic) astrocytes are ideally situated to translate regional synaptic activity to hyperemia (increased flow) as they extend processes that envelop both synapses and vasculature (reviewed in Iadecola and Nedergaard, 2007). Indeed, evidence from in vitro and in vivo twophoton imaging has suggested that stimulus-induced elevations in astrocyte intracellular calcium are positioned to modulate vascular tone (Zonta et al, 2003; Takano et al, 2006; Mulligan and MacVicar, 2004; Winship et al, 2007). These local interactions are purported to occur at the astrocytic endfoot–blood vessel interface (reviewed in Iadecola and Nedergaard, 2007). Regionally, the spatial organization of astrocytes and vasculature should also have implications for matching blood flow to activity. While previous works have examined the interrelationships between astrocytes and microvasculature across cortical lamina, these studies have been conducted using histology and thus may not always faithfully represent the living tissue (White et al, 1981; Tsai et al, 2009). The present work of McCaslin et al (2011) has taken an important step to extend these findings in the live murine brain. Using in vivo two-photon imaging, the authors found that the density of astrocytes showed distinct peaks at 40 to 60 and 440 to 500 mm below the cortical surface, corroborating an earlier report (Tsai et al, 2009). Likewise, the density of capillaries mirrored that of astrocytes, reaching similar peaks at 30 to 40 mm and again at 500 mm; moreover, the average distance between astrocytes and capillaries decreased with increasing cortical depth. This, together with evidence from Tsai et al (2009), who found that neuronal density peaks at 600 mm below the cortical surface, suggests that this columnar depth carries the highest metabolic load. Indeed, it has been recently reported that the fastest changes in dilation occur in diving arterioles and capillaries that are located at this cortical depth (Tian et al, 2010). Both experimental data (Tian et al, 2010) and models (Faraci and Heistad, 1990) have suggested that dilation of local arterioles is accompanied by temporally delayed dilation in upstream arteries. Gap junction-mediated communication between astrocytes has been implicated in the upward propagation of vasodilating signals from active neurons in the parenchyma to pial arteries (Xu et al, 2008). In support of a functional role for an astrocytic network in conducting hemodynamic signals, McCaslin et al (2011) confirm that a syncytium of astrocytes is in contact with all blood vessels below the glia limitans. The laminar variations in astrocyte–vasculature interactions revealed by McCaslin et al (2011) may have important implications for the spatial and temporal matching of blood flow to activity within specific cortical layers. However, delineation of the relative contribution of distinct neuronal populations (reviewed in Cauli and Hamel, 2010) versus astrocytes to hemodynamic responses will require further exploration, perhaps with new optical tools to selectively regulate neuronal and astrocytic activity (Gradinaru et al, 2010).