Large-Scale Calcium Waves Traveling through Astrocytic NetworksIn Vivo

Abstract

Macroscopic changes in cerebral blood flow, such as those captured by functional imaging of the brain, require highly organized, large-scale dynamics of astrocytes, glial cells that interact with both neuronal and cerebrovascular networks. However, astrocyte activity has been studied mainly at the level of individual cells, and information regarding their collective behavior is lacking. In this work, we monitored calcium activity simultaneously from hundreds of mouse hippocampal astrocytes in vivo and found that almost all astrocytes participated en masse in regenerative waves that propagated from cell to cell (referred to here as "glissandi"). Glissandi emerged depending on the neuronal activity and accompanied a reduction in infraslow fluctuations of local field potentials and a decrease in the flow of red blood cells. This novel phenomenon was heretofore overlooked, probably because of the high vulnerability of astrocytes to light damage; glissandi occurred only when observed at much lower laser intensities than previously used.

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

“…5c). However, as TTX treatment alone has been demonstrated to be sufficient to block flavoprotein-dependent autofluorescence in rat somatosensory cortex 29 as well as blocking synchronous, infraslow largescale astrocytic calcium waves 62 , we also examined the dependency of our observed infraslow activity on specifically excitatory glutamatergic transmission and found that DNQX and AP5 treatment also abolished infraslow functional organization (Fig. 5).…”

Intercellular Ca2+Waves: Mechanisms and Function

“…Interestingly, ICWs can also occur spontaneously without specific triggers. Spontaneous ICWs have been observed in retinal pigment epithelial cells (270), the intact retina in vitro and in vivo (193), brain slices of the developing neocortex (394), Bergmann glia (astrocytes in the molecular layer) of the in vivo cerebellum (161), and hippocampal astrocytes in vivo (192). The frequency of these spontaneous ICWs can be increased by lowering extracellular Ca 2ϩ (343,394,413), an effect that may result from increased connexin hemichannel opening and ATP release (11) (see sect.…”

“…Equally important is the fact that in tissue culture, many of the organ characteristics, such as the extracellular matrix, variety of cell types, extent of cell coupling, and cell differentiation, are lost or significantly altered. At present, there are fewer reports of ICWs in vivo in organs like the brain, liver, and lung (161,192,265,292) and therefore, as yet, insufficient supportive data for specific physiological responses of ICWs. However, this situation is rapidly changing.…”

“…For example, excitation with high-energy pulses of infrared light may locally generate free oxygen radicals (due to triple-state excitation) or thermal effects, and these may serve as triggers to stimulate ICWs (389). Conversely, too much laser energy may dampen Ca 2ϩ wave activity (192).…”

Topology Drives Calcium Wave Propagation in 3D Astrocyte Networks

“…In vivo, large regenerative waves spanning all the observable cells are sometimes (though rarely) observed (cf. [14]). Our results indicate that this could be linked to a transient decrease of gapjunction coupling levels, effectively leading to a reduction of the network mean degree, or to a restriction of gap-junction coupling to a few neighbors.…”