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Astrocyte Ca2+ signalling: an unexpected complexity

Nature Reviews Neuroscience volume 15, pages 327–335 (2014)Cite this article

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Abstract

Astrocyte Ca2+ signalling has been proposed to link neuronal information in different spatial–temporal dimensions to achieve a higher level of brain integration. However, some discrepancies in the results of recent studies challenge this view and highlight key insufficiencies in our current understanding. In parallel, new experimental approaches that enable the study of astrocyte physiology at higher spatial–temporal resolution in intact brain preparations are beginning to reveal an unexpected level of compartmentalization and sophistication in astrocytic Ca2+ dynamics. This newly revealed complexity needs to be attentively considered in order to understand how astrocytes may contribute to brain information processing.

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Figure 1: Diversity of endogenous Ca2+ activity in a mature hippocampal astrocyte in situ: Ca2+ signals in cell body and processes are different.
Figure 2: An emerging view: astrocytes display structural–functional heterogeneity that shapes the diversity of Ca2+ responses.
Figure 3: Different astrocytic Ca2+ signalling pathways may contribute to different forms of hippocampal LTP.

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References

  1. Dani, J. W., Chernjavsky, A. & Smith, S. J. Neuronal activity triggers calcium waves in hippocampal astrocyte networks. Neuron 8, 429–440 (1992).

    CAS  PubMed  Google Scholar 

  2. Porter, J. T. & McCarthy, K. D. Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J. Neurosci. 16, 5073–5081 (1996).

    CAS  PubMed  Google Scholar 

  3. Pasti, L., Volterra, A., Pozzan, T. & Carmignoto, G. Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J. Neurosci. 17, 7817–7830 (1997).

    CAS  PubMed  Google Scholar 

  4. Wang, X. et al. Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nature Neurosci. 9, 816–823 (2006).

    CAS  PubMed  Google Scholar 

  5. Petzold, G. C., Albeanu, D. F., Sato, T. F. & Murthy, V. N. Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways. Neuron 58, 897–910 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Schummers, J., Yu, H. & Sur, M. Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320, 1638–1643 (2008).

    CAS  PubMed  Google Scholar 

  7. Nimmerjahn, A., Mukamel, E. A. & Schnitzer, M. J. Motor behavior activates Bergmann glial networks. Neuron 62, 400–412 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Gourine, A. V. et al. Astrocytes control breathing through pH-dependent release of ATP. Science 329, 571–575 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Volterra, A. & Meldolesi, J. Astrocytes, from brain glue to communication elements: the revolution continues. Nature Rev. Neurosci. 6, 626–640 (2005).

    CAS  Google Scholar 

  10. Perea, G., Navarrete, M. & Araque, A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 32, 421–431 (2009).

    CAS  PubMed  Google Scholar 

  11. Halassa, M. M. & Haydon, P. G. Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu. Rev. Physiol. 72, 335–355 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Volterra, A. in Neuroglia (eds Kettenmann, H. & Ransom, B. R.) 816–823 (Oxford Univ. Press, 2013).

    Google Scholar 

  13. Waldo, G. L. & Harden, T. K. Agonist binding and Gq-stimulating activities of the purified human P2Y1 receptor. Mol. Pharmacol. 65, 426–436 (2004).

    CAS  PubMed  Google Scholar 

  14. Pinto, J. C. et al. Cannabinoid receptor binding and agonist activity of amides and esters of arachidonic acid. Mol. Pharmacol. 46, 516–522 (1994).

    CAS  PubMed  Google Scholar 

  15. Bowery, N. G., Hill, D. R. & Hudson, A. L. Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes. Br. J. Pharmacol. 78, 191–206 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Nash, M. S. et al. Determinants of metabotropic glutamate receptor-5-mediated Ca2+ and inositol 1,4,5-trisphosphate oscillation frequency. Receptor density versus agonist concentration. J. Biol. Chem. 277, 35947–35960 (2002).

    CAS  PubMed  Google Scholar 

  17. Berridge, M. J., Bootman, M. D. & Roderick, H. L. Calcium signalling: dynamics, homeostasis and remodelling. Nature Rev. Mol. Cell Biol. 4, 517–529 (2003).

    CAS  Google Scholar 

  18. Rizzuto, R. & Pozzan, T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol. Rev. 86, 369–408 (2006).

    CAS  PubMed  Google Scholar 

  19. Verkhratsky, A. & Kirchhoff, F. NMDA receptors in glia. Neuroscientist 13, 28–37 (2007).

    CAS  PubMed  Google Scholar 

  20. Matsui, K. & Jahr, C. E. Exocytosis unbound. Curr. Opin. Neurobiol. 16, 305–311 (2006).

    CAS  PubMed  Google Scholar 

  21. Kirischuk, S., Kettenmann, H. & Verkhratsky, A. Na+/Ca2+ exchanger modulates kainate-triggered Ca2+ signaling in Bergmann glial cells in situ. FASEB J. 11, 566–572 (1997).

    CAS  PubMed  Google Scholar 

  22. Doengi, M. et al. GABA uptake-dependent Ca2+ signaling in developing olfactory bulb astrocytes. Proc. Natl Acad. Sci. USA 106, 17570–17575 (2009).

    CAS  PubMed  Google Scholar 

  23. Parri, H. R., Gould, T. M. & Crunelli, V. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nature Neurosci. 4, 803–812 (2001).

    CAS  PubMed  Google Scholar 

  24. Nett, W. J., Oloff, S. H. & McCarthy, K. D. Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. J. Neurophysiol. 87, 528–537 (2002).

    PubMed  Google Scholar 

  25. Aguado, F., Espinosa-Parrilla, J. F., Carmona, M. A. & Soriano, E. Neuronal activity regulates correlated network properties of spontaneous calcium transients in astrocytes in situ. J. Neurosci. 22, 9430–9444 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Honsek, S. D., Walz, C., Kafitz, K. W. & Rose, C. R. Astrocyte calcium signals at Schaffer collateral to CA1 pyramidal cell synapses correlate with the number of activated synapses but not with synaptic strength. Hippocampus 22, 29–42 (2012).

    CAS  PubMed  Google Scholar 

  27. Shigetomi, E., Tong, X., Kwan, K. Y., Corey, D. P. & Khakh, B. S. TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nature Neurosci. 15, 70–80 (2012).

    CAS  Google Scholar 

  28. Shigetomi, E., Jackson-Weaver, O., Huckstepp, R. T., O'Dell, T. J. & Khakh, B. S. TRPA1 channels are regulators of astrocyte basal calcium levels and long-term potentiation via constitutive D-serine release. J. Neurosci. 33, 10143–10153 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Pasti, L., Zonta, M., Pozzan, T., Vicini, S. & Carmignoto, G. Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate. J. Neurosci. 21, 477–484 (2001).

    CAS  PubMed  Google Scholar 

  30. Bezzi, P. et al. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nature Neurosci. 7, 613–620 (2004).

    CAS  PubMed  Google Scholar 

  31. Marchaland, J. et al. Fast subplasma membrane Ca2+ transients control exo-endocytosis of synaptic-like microvesicles in astrocytes. J. Neurosci. 28, 9122–9132 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Woo, D. H. et al. TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151, 25–40 (2012).

    CAS  PubMed  Google Scholar 

  33. Parpura, V. et al. Glutamate-mediated astrocyte-neuron signalling. Nature 369, 744–747 (1994).

    CAS  PubMed  Google Scholar 

  34. Bezzi, P. et al. Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391, 281–285 (1998).

    CAS  PubMed  Google Scholar 

  35. Bezzi, P. & Volterra, A. A neuron–glia signalling network in the active brain. Curr. Opin. Neurobiol. 11, 387–394 (2001).

    CAS  PubMed  Google Scholar 

  36. Shigetomi, E., Bowser, D. N., Sofroniew, M. V. & Khakh, B. S. Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J. Neurosci. 28, 6659–6663 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Montana, V., Ni, Y., Sunjara, V., Hua, X. & Parpura, V. Vesicular glutamate transporter-dependent glutamate release from astrocytes. J. Neurosci. 24, 2633–2642 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Mothet, J. P. et al. Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc. Natl Acad. Sci. USA 102, 5606–5611 (2005).

    CAS  PubMed  Google Scholar 

  39. Santello, M., Bezzi, P. & Volterra, A. TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus. Neuron 69, 988–1001 (2011).

    CAS  PubMed  Google Scholar 

  40. Fiacco, T. A. & McCarthy, K. D. Intracellular astrocyte calcium waves in situ increase the frequency of spontaneous AMPA receptor currents in CA1 pyramidal neurons. J. Neurosci. 24, 722–732 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Fellin, T. et al. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43, 729–743 (2004).

    CAS  PubMed  Google Scholar 

  42. Pascual, O. et al. Astrocytic purinergic signaling coordinates synaptic networks. Science 310, 113–116 (2005).

    CAS  PubMed  Google Scholar 

  43. Panatier, A. et al. Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125, 775–784 (2006).

    CAS  PubMed  Google Scholar 

  44. Jourdain, P. et al. Glutamate exocytosis from astrocytes controls synaptic strength. Nature Neurosci. 10, 331–339 (2007).

    CAS  PubMed  Google Scholar 

  45. Perea, G. & Araque, A. Astrocytes potentiate transmitter release at single hippocampal synapses. Science 317, 1083–1086 (2007).

    CAS  PubMed  Google Scholar 

  46. Panatier, A. et al. Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 146, 785–798 (2011).

    CAS  PubMed  Google Scholar 

  47. Liu, Q. S., Xu, Q., Arcuino, G., Kang, J. & Nedergaard, M. Astrocyte-mediated activation of neuronal kainate receptors. Proc. Natl Acad. Sci. USA 101, 3172–3177 (2004).

    CAS  PubMed  Google Scholar 

  48. Agulhon, C., Fiacco, T. A. & McCarthy, K. D. Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science 327, 1250–1254 (2010).

    CAS  PubMed  Google Scholar 

  49. Fiacco, T. A. et al. Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron 54, 611–626 (2007).

    CAS  PubMed  Google Scholar 

  50. Henneberger, C., Papouin, T., Oliet, S. H. & Rusakov, D. A. Long-term potentiation depends on release of D-serine from astrocytes. Nature 463, 232–236 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Navarrete, M. et al. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity. PLoS Biol. 10, e1001259 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Petravicz, J., Fiacco, T. A. & McCarthy, K. D. Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J. Neurosci. 28, 4967–4973 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Serrano, A., Haddjeri, N., Lacaille, J. C. & Robitaille, R. GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression. J. Neurosci. 26, 5370–5382 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Navarrete, M. & Araque, A. Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes. Neuron 68, 113–126 (2010).

    CAS  PubMed  Google Scholar 

  55. Di Castro, M. A. et al. Local Ca2+ detection and modulation of synaptic release by astrocytes. Nature Neurosci. 14, 1276–1284 (2011).

    CAS  PubMed  Google Scholar 

  56. Poskanzer, K. E. & Yuste, R. Astrocytic regulation of cortical UP states. Proc. Natl Acad. Sci. USA 108, 18453–18458 (2011).

    CAS  PubMed  Google Scholar 

  57. Min, R. & Nevian, T. Astrocyte signaling controls spike timing-dependent depression at neocortical synapses. Nature Neurosci. 15, 746–753 (2012).

    CAS  PubMed  Google Scholar 

  58. Takata, N. et al. Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. J. Neurosci. 31, 18155–18165 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Han, J. et al. Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD. Cell 148, 1039–1050 (2012).

    CAS  PubMed  Google Scholar 

  60. Chen, N. et al. Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes. Proc. Natl Acad. Sci. USA 109, E2832–E2841 (2012).

    CAS  PubMed  Google Scholar 

  61. Grosche, J. et al. Microdomains for neuron–glia interaction: parallel fiber signaling to Bergmann glial cells. Nature Neurosci. 2, 139–143 (1999).

    CAS  PubMed  Google Scholar 

  62. Matyash, V., Filippov, V., Mohrhagen, K. & Kettenmann, H. Nitric oxide signals parallel fiber activity to Bergmann glial cells in the mouse cerebellar slice. Mol. Cell Neurosci. 18, 664–670 (2001).

    CAS  PubMed  Google Scholar 

  63. Perea, G. & Araque, A. Properties of synaptically evoked astrocyte calcium signal reveal synaptic information processing by astrocytes. J. Neurosci. 25, 2192–2203 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. De Pitta, M. et al. Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity. Front. Comput. Neurosci. 6, 98 (2012).

    PubMed  PubMed Central  Google Scholar 

  65. Shigetomi, E. et al. Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses. J. Gen. Physiol. 141, 633–647 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Smith, I. F. & Parker, I. Imaging the quantal substructure of single IP3R channel activity during Ca2+ puffs in intact mammalian cells. Proc. Natl Acad. Sci. USA 106, 6404–6409 (2009).

    CAS  PubMed  Google Scholar 

  67. Clarke, L. E. & Barres, B. A. Emerging roles of astrocytes in neural circuit development. Nature Rev. Neurosci. 14, 311–321 (2013).

    CAS  Google Scholar 

  68. Tanaka, M. et al. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses. Mol. Brain 6, 6 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Gordon, G. R. et al. Astrocyte-mediated distributed plasticity at hypothalamic glutamate synapses. Neuron 64, 391–403 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Schulz, K. et al. Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex. Nature Methods 9, 597–602 (2012).

    CAS  PubMed  Google Scholar 

  71. Wang, F. et al. Astrocytes modulate neural network activity by Ca2+-dependent uptake of extracellular K+. Sci. Signal. 5, ra26 (2012).

    PubMed  PubMed Central  Google Scholar 

  72. Wang, F., Xu, Q., Wang, W., Takano, T. & Nedergaard, M. Bergmann glia modulate cerebellar Purkinje cell bistability via Ca2+-dependent K+ uptake. Proc. Natl Acad. Sci. USA 109, 7911–7916 (2012).

    CAS  PubMed  Google Scholar 

  73. Li, W., Llopis, J., Whitney, M., Zlokarnik, G. & Tsien, R. Y. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392, 936–941 (1998).

    CAS  PubMed  Google Scholar 

  74. Dolmetsch, R. E., Xu, K. & Lewis, R. S. Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392, 933–936 (1998).

    CAS  PubMed  Google Scholar 

  75. De Koninck, P. & Schulman, H. Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science 279, 227–230 (1998).

    CAS  PubMed  Google Scholar 

  76. Hirase, H., Qian, L., Bartho, P. & Buzsaki, G. Calcium dynamics of cortical astrocytic networks in vivo. PLoS Biol. 2, E96 (2004).

    PubMed  PubMed Central  Google Scholar 

  77. Nimmerjahn, A., Kirchhoff, F., Kerr, J. N. & Helmchen, F. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nature Methods 1, 31–37 (2004).

    CAS  PubMed  Google Scholar 

  78. Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T. & Bacskai, B. J. Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323, 1211–1215 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Sun, W. et al. Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339, 197–200 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Grienberger, C. & Konnerth, A. Imaging calcium in neurons. Neuron 73, 862–885 (2012).

    CAS  PubMed  Google Scholar 

  81. Neher, E. & Augustine, G. J. Calcium gradients and buffers in bovine chromaffin cells. J. Physiol. 450, 273–301 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Helmchen, F., Imoto, K. & Sakmann, B. Ca2+ buffering and action potential-evoked Ca2+ signaling in dendrites of pyramidal neurons. Biophys. J. 70, 1069–1081 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Tian, L., Hires, S. A. & Looger, L. L. Imaging neuronal activity with genetically encoded calcium indicators. Cold Spring Harb. Protoc. 2012, 647–656 (2012).

    PubMed  Google Scholar 

  84. Akerboom, J. et al. Optimization of a GCaMP calcium indicator for neural activity imaging. J. Neurosci. 32, 13819–13840 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Thomas, D. et al. A comparison of fluorescent Ca2+ indicator properties and their use in measuring elementary and global Ca2+ signals. Cell Calcium 28, 213–223 (2000).

    CAS  PubMed  Google Scholar 

  86. Miyawaki, A. et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388, 882–887 (1997).

    CAS  PubMed  Google Scholar 

  87. Yamada, Y. & Mikoshiba, K. Quantitative comparison of novel GCaMP-type genetically encoded Ca2+ indicators in mammalian neurons. Front. Cell Neurosci. 6, 41 (2012).

    PubMed  PubMed Central  Google Scholar 

  88. Margolis, D. J. et al. Reorganization of cortical population activity imaged throughout long-term sensory deprivation. Nature Neurosci. 15, 1539–1546 (2012).

    CAS  PubMed  Google Scholar 

  89. Lutcke, H., Margolis, D. J. & Helmchen, F. Steady or changing? Long-term monitoring of neuronal population activity. Trends Neurosci. 36, 375–384 (2013).

    CAS  PubMed  Google Scholar 

  90. Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 6, 875–881 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Chen, Q. et al. Imaging neural activity using Thy1-GCaMP transgenic mice. Neuron 76, 297–308 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Hasan, M. T. et al. Functional fluorescent Ca2+ indicator proteins in transgenic mice under TET control. PLoS Biol. 2, e163 (2004).

    PubMed  PubMed Central  Google Scholar 

  93. Pfrieger, F. W. & Slezak, M. Genetic approaches to study glial cells in the rodent brain. Glia 60, 681–701 (2012).

    PubMed  Google Scholar 

  94. Ohkura, M. et al. Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals. PLoS ONE 7, e51286 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Sun, X. R. et al. Fast GCaMPs for improved tracking of neuronal activity. Nature Commun. 4, 2170 (2013).

    Google Scholar 

  96. Chen, T. W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Smith, K. Neuroscience: settling the great glia debate. Nature 468, 160–162 (2010).

    CAS  PubMed  Google Scholar 

  98. Duffy, S. & MacVicar, B. A. Adrenergic calcium signaling in astrocyte networks within the hippocampal slice. J. Neurosci. 15, 5535–5550 (1995).

    CAS  PubMed  Google Scholar 

  99. Arizono, M. et al. Receptor-selective diffusion barrier enhances sensitivity of astrocytic processes to metabotropic glutamate receptor stimulation. Sci. Signal. 5, ra27 (2012).

    PubMed  Google Scholar 

  100. Lavialle, M. et al. Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc. Natl Acad. Sci. USA 108, 12915–12919 (2011).

    CAS  PubMed  Google Scholar 

  101. Tonnesen, J. & Nagerl, U. V. Two-color STED imaging of synapses in living brain slices. Methods Mol. Biol. 950, 65–80 (2013).

    PubMed  Google Scholar 

  102. Wilms, C. D., Schmidt, H. & Eilers, J. Quantitative two-photon Ca2+ imaging via fluorescence lifetime analysis. Cell Calcium 40, 73–79 (2006).

    CAS  PubMed  Google Scholar 

  103. Akerboom, J. et al. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front. Mol. Neurosci. 6, 2 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Pastrana, E. Calcium sensors reach new heights. Nature Methods 10, 824 (2013).

    CAS  PubMed  Google Scholar 

  105. Rusakov, D. A., Zheng, K. & Henneberger, C. Astrocytes as regulators of synaptic function: a quest for the Ca2+ master key. Neuroscientist 17, 513–523 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Katona, G. et al. Fast two-photon in vivo imaging with three-dimensional random-access scanning in large tissue volumes. Nature Methods 9, 201–208 (2012).

    CAS  PubMed  Google Scholar 

  107. Bushong, E. A., Martone, M. E., Jones, Y. Z. & Ellisman, M. H. Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J. Neurosci. 22, 183–192 (2002).

    CAS  PubMed  Google Scholar 

  108. Halassa, M. M., Fellin, T., Takano, H., Dong, J. H. & Haydon, P. G. Synaptic islands defined by the territory of a single astrocyte. J. Neurosci. 27, 6473–6477 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Gordon, G. R., Choi, H. B., Rungta, R. L., Ellis-Davies, G. C. & MacVicar, B. A. Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456, 745–749 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Yasuda, R. et al. Imaging calcium concentration dynamics in small neuronal compartments. Sci. STKE 2004, pl5 (2004).

    PubMed  Google Scholar 

  111. Nevian, T. & Helmchen, F. Calcium indicator loading of neurons using single-cell electroporation. Pflugers Arch. 454, 675–688 (2007).

    CAS  PubMed  Google Scholar 

  112. Darabid, H., Arbour, D. & Robitaille, R. Glial cells decipher synaptic competition at the mammalian neuromuscular junction. J. Neurosci. 33, 1297–1313 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Nolte, C. et al. GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia 33, 72–86 (2001).

    CAS  PubMed  Google Scholar 

  114. Tokuyasu, K. T. A technique for ultracryotomy of cell suspensions and tissues. J. Cell Biol. 57, 551–565 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Chao, T. I., Rickmann, M. & Wolff, J. R. in The Tripartite Synapse: Glia in Synaptic Transmission (eds Volterra, A., Magistretti, P. J. & Haydon, P. G.) 3–23 (Oxford Univ. Press, 2002).

    Google Scholar 

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Acknowledgements

Research in the Volterra laboratory is supported by the ERC Advanced grant 340368 “Astromnesis” and by Swiss National Science Foundation grants 31003A 140999, NCCR “Synapsy” and NCCR “Transcure”.

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  1. Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, Lausanne, 1005, Switzerland

    Andrea Volterra, Nicolas Liaudet & Iaroslav Savtchouk

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Correspondence to Andrea Volterra.

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Volterra, A., Liaudet, N. & Savtchouk, I. Astrocyte Ca2+ signalling: an unexpected complexity. Nat Rev Neurosci 15, 327–335 (2014). https://doi.org/10.1038/nrn3725

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