Radially expanding transglial calcium waves in the intact cerebellum. Proc Natl Acad Sci USA

Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 03/2009; 106(9):3496-501. DOI: 10.1073/pnas.0809269106
Source: PubMed


Multicellular glial calcium waves may locally regulate neural activity or brain energetics. Here, we report a diffusion-driven astrocytic signal in the normal, intact brain that spans many astrocytic processes in a confined volume without fully encompassing any one cell. By using 2-photon microscopy in rodent cerebellar cortex labeled with fluorescent indicator dyes or the calcium-sensor protein G-CaMP2, we discovered spontaneous calcium waves that filled approximately ellipsoidal domains of Bergmann glia processes. Waves spread in 3 dimensions at a speed of 4-11 microm/s to a diameter of approximately 50 microm, slowed during expansion, and were reversibly blocked by P2 receptor antagonists. Consistent with the hypothesis that ATP acts as a diffusible trigger of calcium release waves, local ejection of ATP triggered P2 receptor-mediated waves that were refractory to repeated activation. Transglial waves represent a means for purinergic signals to act with local specificity to modulate activity or energetics in local neural circuits.

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    • "Yet, it was later acknowledged that astroglia exhibit a special form of excitability that is based on variations in the intracellular concentration of Ca 2+ ions (Charles et al., 1991; Cornell-Bell et al., 1990). Studies performed in acute brain slices and, more recently, in vivo allowed to determine that astrocytic [Ca 2+ ] i changes can occur spontaneously (Aguado et al., 2002; Hirase et al., 2004; Hoogland et al., 2009; Navarrete et al., 2013; Nett et al., 2002; Nimmerjahn et al., 2009; Panatier et al., 2011; Parri et al., 2001), or can be evoked in response to synaptic activity (Dani et al., 1992; Di Castro et al., 2011; Dombeck et al., 2007; Gourine et al., 2010; Jourdain et al., 2007; Nimmerjahn et al., 2009; Pasti et al., 1997; Paukert et al., 2014; Petzold et al., 2008; Porter and McCarthy, 1995a,b, 1996; Santello et al., 2011; Schummers et al., 2008; Wang et al., 2006; Winship et al., 2007). In addition, there is evidence indicating that they can be mediated also by transient receptor potential A1 channels (Shigetomi et al., 2012, 2013a). "
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    ABSTRACT: Recent breakthroughs in neuroscience have led to the awareness that we should revise our traditional mode of thinking and studying the CNS, i.e. by isolating the privileged network of "intelligent" synaptic contacts. We may instead need to contemplate all the variegate communications occurring between the different neural cell types, and centrally involving the astrocytes. Basically, it appears that a single astrocyte should be considered as a core that receives and integrates information from thousands of synapses, other glial cells and the blood vessels. In turn, it generates complex outputs that control the neural circuitry and coordinate it with the local microcirculation. Astrocytes thus emerge as the possible fulcrum of the functional homeostasis of the healthy CNS. Yet, evidence indicates that the bridging properties of the astrocytes can change in parallel with, or as a result of, the morphological, biochemical and functional alterations these cells undergo upon injury or disease. As a consequence, they have the potential to transform from supportive friends and interactive partners for neurons into noxious foes. In this review, we summarize the currently available knowledge on the contribution of astrocytes to the functioning of the CNS and what goes wrong in various pathological conditions, with a particular focus on amyotrophic lateral sclerosis, Alzheimer's disease and ischemia. The observations described convincingly demonstrate that the development and progression of several neurological disorders involve the de-regulation of a finely tuned interplay between multiple cell populations. Thus, it seems that a better understanding of the mechanisms governing the integrated communication and detrimental responses of the astrocytes as well as their impact towards the homeostasis and performance of the CNS is fundamental to open novel therapeutic perspectives. Copyright © 2015. Published by Elsevier Ltd.
    Progress in Neurobiology 04/2015; 29. DOI:10.1016/j.pneurobio.2015.04.003 · 9.99 Impact Factor
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    • "ICWs can be initiated in the in vivo retina and brain by various triggers; however, an important concern is that such experimental stimulation (electrical, specific receptor ligands, photoactivation of Ca 2+ —see below) is often much stronger than can be reasonably expected under normal physiological conditions. Spontaneous ICWs have been reported in the cerebellum in vivo (Hoogland et al. 2009), but the wave activity seems to disappear when the animals start locomotor activity (Nimmerjahn et al. 2009). Pathological conditions are likely to provide stronger cellular and molecular stimuli for ICWs compared to the physiological situation. "
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    Cold Spring Harbor Protocols 03/2015; 2015(3):pdb.top066068. DOI:10.1101/pdb.top066068 · 4.63 Impact Factor
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    • "Since the probability of finding these neurons is relatively low [1 GoC every 430 GrCs (Korbo et al., 1993), 1 Lugaro cell/15 PCs (Dieudonné and Dumoulin, 2000)], it is unlikely that they contributed significantly to signal generation in our recordings. It should also be noted that a contribution of calcium signals generated by glial cells (Hoogland et al., 2009; Hoogland and Kuhn, 2010) cannot be completely ruled out. However, such a contribution is unlikely, given that the typical calcium transients in astrocytes and glial cells show slower kinetics and larger latencies compared with those of neuronal signals and glial calcium waves usually fluctuate independently of synaptic inputs (Hoogland et al., 2009; Hoogland and Kuhn, 2010). "
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