Origins of blood volume change due to glutamatergic synaptic activity at astrocytes abutting on arteriolar smooth muscle cells

Modeling the contribution of neuron-astrocyte cross talk to slow blood oxygenation level-dependent signal oscillations

“…In the context of fMRI, astrocytic Ca 2ϩ signaling is all-important, because a substantial component underlying functional hyperemia is mediated by the action of vasoactive compounds released by astrocytes in response to Ca 2ϩ (Bennett et al 2008a(Bennett et al , 2008bIadecola 2004;Rossi 2006). We found that the energy demand associated with Ca 2ϩ signaling and the Ca 2ϩ -dependent changes in hemodynamic parameters can generate detectable BOLD oscillations.…”

“…Therefore, synchronization would be not necessary to detect the effect of small, independent clusters of activated astrocytes on macroscopic variables. Accordingly, theoretical modeling indicates that only a few astrocytes are sufficient to produce a measurable change in the BOLD signal (Bennett et al 2008a(Bennett et al , 2008b. Further experimental research is needed to establish the vascular (e.g., CBF) and metabolic (e.g., CMR O 2 ) contribution of single astrocytes on voxel-sized volumes.…”

“…The parameters K 0.5 ϭ 400 nmol/l and h r ϭ 4 were chosen to reproduce mathematical modeling results of Ca 2ϩ -induced release of vasoactive agents at the astrocyte-arteriole interface and their effect on CBF and cerebral blood volume (CBV) obtained elsewhere (Bennett et al 2008a(Bennett et al , 2008b. This circumvents the explicit modeling of the entire Ca 2ϩ -dependent pathway leading to vasodilation (see Bennett et al 2008a for details). Theoretical calculations predict that a single Ca 2ϩ wave within a few activated astrocytes can induce a blood flow increase of ϳ13% during glutamatergic synaptic activity (Bennett et al 2008a).…”

“…This circumvents the explicit modeling of the entire Ca 2ϩ -dependent pathway leading to vasodilation (see Bennett et al 2008a for details). Theoretical calculations predict that a single Ca 2ϩ wave within a few activated astrocytes can induce a blood flow increase of ϳ13% during glutamatergic synaptic activity (Bennett et al 2008a). This is likely to represent a conservative estimate, because Ca 2ϩ waves have the potential to freely propagate throughout gap junctions within up to 30 different astrocytes (Tian et al 2006).…”

“…In particular, Ca 2ϩ elevations in astrocytes initiate a metabolic cascade that participates in smooth muscle cells activation and subsequent response of adjacent arterioles (Bennett et al 2008a). The fact that astrocytes are intermediary in synaptic transmission-mediated functional hyperemia is relevant for functional magnetic resonance (fMRI) studies ), in particular those showing low-frequency fluctuations in the blood oxygenation level-dependent (BOLD) signal (Fox et al 2005).…”