Calcium dynamics in astrocyte processes during neurovascular coupling

Otsu, Yo; Couchman, Kiri; Lyons, Declan G; Collot, Mayeul; Agarwal, Amit; Mallet, Jean‐Maurice; Pfrieger, Frank W.; Bergles, Dwight E.; Charpak, Serge

doi:10.1038/nn.3906

Cited by 245 publications

(256 citation statements)

References 50 publications

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“…1E) and a greater number of signals ( Fig. 1D) than endfeet or somata, comparable to previous reports with other calcium indicators and in other brain regions (Shigetomi et al 2013;Gee et al 2014;Kanemaru et al 2014;Otsu et al 2015;Srinivasan et al 2015;Tang et al 2015). A previous study has also detected three different populations of GCaMP6s peaks in astrocytes: single peaks, multi peaks, and plateaus (Bonder and McCarthy 2014).…”

Section: Discussionsupporting

confidence: 91%

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

et al. 2016

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Localized, heterogeneous calcium transients occur throughout astrocytes, but the characteristics and long-term stability of these signals, particularly in response to sensory stimulation, remain unknown. Here, we used a genetically encoded calcium indicator and an activity-based image analysis scheme to monitor astrocyte calcium activity in vivo. We found that different subcellular compartments (processes, somata, and endfeet) displayed distinct signaling characteristics. Closer examination of individual signals showed that sensory stimulation elevated the number of specific types of calcium peaks within astrocyte processes and somata, in a cortical layer-dependent manner, and that the signals became more synchronous upon sensory stimulation. Although mice genetically lacking astrocytic IP3R-dependent calcium signaling (Ip3r2−/−) had fewer signal peaks, the response to sensory stimulation was sustained, suggesting other calcium pathways are also involved. Long-term imaging of astrocyte populations revealed that all compartments reliably responded to stimulation over several months, but that the location of the response within processes may vary. These previously unknown characteristics of subcellular astrocyte calcium signals provide new insights into how astrocytes may encode local neuronal circuit activity. AbstractLocalized, heterogeneous calcium transients occur throughout astrocytes, but the characteristics and

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Section: Discussionsupporting

confidence: 91%

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

et al. 2016

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“…Ca 2+ fluorescence signals and 2-NBDG fluorescence signals were analyzed in regions of interest (ROIs) covering the somata of oligodendroglial cells. Normalized changes of Rhod-2 fluorescence intensities were calculated as ΔF/F=(F−F0)/F0 (F, fluorescence intensity; F0, baseline intensity) (Otsu et al, 2015). And the relative changes of 2-NBDG fluorescence intensities were calculated as the (F−F0)/S [F, 2-NBDG fluorescence intensity at end time point; F0, baseline 2-NBDG fluorescence intensity; S, time (seconds) from start point of treatment to the end time point of experiment].…”

Section: Intracellular Camentioning

confidence: 99%

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Niu

et al. 2016

Journal of Cell Science

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Oligodendrocyte precursor cells (OPCs) undergo a series of energyconsuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca 2+ elevation in OPCs, indicating a Ca 2+ -dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energymetabolism-directed oligodendroglial-targeted therapies.

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“…102 Further recent studies have confirmed that astrocytic, fast Ca 2þ transients that occur in the cell soma, fine processes, and endfeet reliably precede functional hyperemia in adult mice in vivo. 103,104 Thus, it appears that astrocytes from IP 3 R2-knockout mice do continue to engage in Ca 2þ signaling, perhaps due to compensatory upregulation of other IP 3 R isoforms, likely on a spatial and temporal scale that previous studies were unable to detect.…”

Section: Ip 3 Rsmentioning

confidence: 99%

Ion channel networks in the control of cerebral blood flow

Longden

Hill-Eubanks

Nelson

2015

J Cereb Blood Flow Metab

114

115

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One hundred and twenty five years ago, Roy and Sherrington made the seminal observation that neuronal stimulation evokes an increase in cerebral blood flow.1 Since this discovery, researchers have attempted to uncover how the cells of the neurovascular unit-neurons, astrocytes, vascular smooth muscle cells, vascular endothelial cells and pericytes-coordinate their activity to control this phenomenon. Recent work has revealed that ionic fluxes through a diverse array of ion channel species allow the cells of the neurovascular unit to engage in multicellular signaling processes that dictate local hemodynamics. In this review we center our discussion on two major themes: (1) the roles of ion channels in the dynamic modulation of parenchymal arteriole smooth muscle membrane potential, which is central to the control of arteriolar diameter and therefore must be harnessed to permit changes in downstream cerebral blood flow, and (2) the striking similarities in the ion channel complements employed in astrocytic endfeet and endothelial cells, enabling dual control of smooth muscle from either side of the blood-brain barrier. We conclude with a discussion of the emerging roles of pericyte and capillary endothelial cell ion channels in neurovascular coupling, which will provide fertile ground for future breakthroughs in the field.

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Calcium dynamics in astrocyte processes during neurovascular coupling

Cited by 245 publications

References 50 publications

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

Long-term In Vivo Calcium Imaging of Astrocytes Reveals Distinct Cellular Compartment Responses to Sensory Stimulation

Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage

Ion channel networks in the control of cerebral blood flow

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