, 2006, Howarth and Attwell, 2006 and Paulson and Newman, 1987). However, the current generated by glutamate transport is small compared to that generated by astrocytic K+ uptake at the synaptic cleft in olfactory glomeruli (De Saint Jan and Westbrook, 2005), and it seems unlikely that the blockade of a comparatively small current would reduce functional hyperemia as much as observed. Second, CBF may increase as a result of metabolic activation induced by glutamate uptake. Sodium/glutamate

cotransport consumes energy for the restoration of the ionic gradient by the Na+-/K+-ATPase, and for the conversion of glutamate to glutamine. While the contribution of these processes to the brain’s energy

budget is small (Attwell and Laughlin, 2001), glutamate Vorinostat research buy uptake into astrocytes also directly initiates astrocytic nonoxidative glycolysis and lactate release (Pellerin, 2005). Lactate itself may initiate vasodilation (Gordon et al., 2008), but it is also possible that sodium ions cotransported into astrocytes with glutamate may trigger a vasoactive click here pathway. Sodium ions shuttled into astrocytes by this cotransport propagate as interastrocytic sodium waves in cell cultures (Bernardinelli et al., 2004), and they have also been shown to couple synaptic activity and astrocytic nonoxidative glucose consumption (Voutsinos-Porche et al., 2003). This stimulation of nonoxidative glycolysis in astrocytes is thought to underlie the disproportionate rise of CBF and glucose compared to a smaller increase in oxygen consumption—the mismatch that forms the basis of functional brain imaging (Magistretti and Pellerin, 1999). Therefore, glutamate transport into astrocytes may simultaneously activate functional hyperemia and nonoxidative glycolysis in astrocytes, and may contribute to the high temporal and spatial correlation of

CBF increase and glucose consumption observed in functional brain imaging (Raichle and Mintun, 2006). Advances in imaging and cellular manipulation may be harnessed to overcome the oxyclozanide uncertainties regarding the role of astrocytic molecular agents in functional hyperemia. Optical imaging during physiological activity can, in principle, be extended to any small molecule for which there is an appropriate fluorescent indicator (Zhang et al., 2002). Genetic manipulations may also be valuable, particularly if the perturbations can be performed in a cell-type-specific and temporally precise manner (Kennedy et al., 2010). Methods to stimulate or downregulate the expression of genes, such as those for glutamate transporters, specifically in mature astrocytes are increasingly becoming available (Colin et al., 2009).