Astrocyte calcium elevations: Properties, propagation, and effects on brain signaling

The possibility that astrocytes are involved in brain signaling began to emerge in the late 1970s, when it was first shown that astroglia in vitro possess numerous receptors for neurotransmitters. It was later demonstrated that cultured astroglia and astrocytes in situ respond to neurotransmitters with increases in intracellular second messengers, including cyclic AMP and calcium. Astrocyte calcium responses have since been extensively studied both in culture and in intact tissue. We continue to gather information regarding the various compounds able to trigger astrocyte calcium increases, as well as the mechanisms involved in their initiation, propagation as a calcium wave within and between astrocytes, and effects on signaling within the brain. This review will focus on each of these aspects of astrocyte calcium regulation, and attempt to sort out which effects are more likely to occur in developmental, pathological, and physiological conditions. While we have come far in our understanding of the properties or potential of astrocytes' ability to signal to neurons using our array of pharmacological tools, we still understand very little regarding the level of involvement of astrocyte signaling in normal brain physiology. © 2006 Wiley‐Liss, Inc.

[1]  S. Finkbeiner,et al.  Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. , 1990, Science.

[2]  James Watras,et al.  Bell-shaped calcium-response curves of lns(l,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum , 1991, Nature.

[3]  M J Sanderson,et al.  Intercellular propagation of calcium waves mediated by inositol trisphosphate. , 1992, Science.

[4]  S. Waxman,et al.  Expression of voltage-activated ion channels by astrocytes and oligodendrocytes in the hippocampal slice. , 1993, Journal of neurophysiology.

[5]  Fang Liu,et al.  Glutamate-mediated astrocyte–neuron signalling , 1994, Nature.

[6]  T. Basarsky,et al.  Expression of synaptobrevin II, cellubrevin and syntaxin but not SNAP‐25 in cultured astrocytes , 1995, FEBS letters.

[7]  R. Jabs,et al.  Developmental regulation of Na+ and K+ conductances in glial cells of mouse hippocampal brain slices , 1995, Glia.

[8]  T. Pozzan,et al.  Long-lasting Changes of Calcium Oscillations in Astrocytes , 1995, The Journal of Biological Chemistry.

[9]  K. McCarthy,et al.  Hippocampal Astrocytes In Situ Respond to Glutamate Released from Synaptic Terminals , 1996, The Journal of Neuroscience.

[10]  Helmut Kettenmann,et al.  Calcium signalling in glial cells , 1996, Trends in Neurosciences.

[11]  K. McCarthy,et al.  ASTROCYTIC NEUROTRANSMITTER RECEPTORS IN SITU AND IN VIVO , 1997, Progress in Neurobiology.

[12]  T. Pozzan,et al.  Intracellular Calcium Oscillations in Astrocytes: A Highly Plastic, Bidirectional Form of Communication between Neurons and Astrocytes In Situ , 1997, The Journal of Neuroscience.

[13]  L. Venance,et al.  Intercellular calcium signaling and gap junctional communication in astrocytes , 1998, Glia.

[14]  J. E. Franck,et al.  Upregulation of L-Type Ca2+ Channels in Reactive Astrocytes after Brain Injury, Hypomyelination, and Ischemia , 1998, The Journal of Neuroscience.

[15]  A. Araque,et al.  Calcium Elevation in Astrocytes Causes an NMDA Receptor-Dependent Increase in the Frequency of Miniature Synaptic Currents in Cultured Hippocampal Neurons , 1998, The Journal of Neuroscience.

[16]  S. Vicini,et al.  Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons , 1998, The Journal of physiology.

[17]  A. Verkhratsky,et al.  Glial calcium: homeostasis and signaling function. , 1998, Physiological reviews.

[18]  A. Araque,et al.  Glutamate‐dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons , 1998, The European journal of neuroscience.

[19]  S. Goldman,et al.  Astrocyte-mediated potentiation of inhibitory synaptic transmission , 1998, Nature Neuroscience.

[20]  K. Zahs,et al.  Modulation of Neuronal Activity by Glial Cells in the Retina , 1998, The Journal of Neuroscience.

[21]  T. Pozzan,et al.  On the Role of Voltage-Dependent Calcium Channels in Calcium Signaling of Astrocytes In Situ , 1998, The Journal of Neuroscience.

[22]  C. Naus,et al.  Connexins regulate calcium signaling by controlling ATP release. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J Wenzel,et al.  Functional Specialization and Topographic Segregation of Hippocampal Astrocytes , 1998, The Journal of Neuroscience.

[24]  S. Kirischuk,et al.  Glutamate-triggered calcium signalling in mouse Bergmann glial cells in situ: role of inositol-1,4,5-trisphosphate-mediated intracellular calcium release , 1999, Neuroscience.

[25]  A. Reichenbach,et al.  Microdomains for neuron–glia interaction: parallel fiber signaling to Bergmann glial cells , 1999, Nature Neuroscience.

[26]  G. Westbrook,et al.  The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal Synapses In Vitro , 1999, The Journal of Neuroscience.

[27]  Marco Capogna,et al.  Miniature synaptic events maintain dendritic spines via AMPA receptor activation , 1999, Nature Neuroscience.

[28]  S. B. Kater,et al.  ATP Released from Astrocytes Mediates Glial Calcium Waves , 1999, The Journal of Neuroscience.

[29]  R. Weinberg,et al.  Shaping excitation at glutamatergic synapses , 1999, Trends in Neurosciences.

[30]  G. Rumbaugh,et al.  Distinct Synaptic and Extrasynaptic NMDA Receptors in Developing Cerebellar Granule Neurons , 1999, The Journal of Neuroscience.

[31]  P. Haydon,et al.  Imaging Extracellular Waves of Glutamate during Calcium Signaling in Cultured Astrocytes , 2000, The Journal of Neuroscience.

[32]  P. Somogyi,et al.  Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus , 2000, Nature.

[33]  M. Blaustein,et al.  Unloading and refilling of two classes of spatially resolved endoplasmic reticulum Ca2+ stores in astrocytes , 2000, Glia.

[34]  Z Wang,et al.  Direct observation of calcium-independent intercellular ATP signaling in astrocytes. , 2000, Analytical chemistry.

[35]  A. Araque,et al.  SNARE Protein-Dependent Glutamate Release from Astrocytes , 2000, The Journal of Neuroscience.

[36]  R. Swanson,et al.  Astrocyte glutamate transport: Review of properties, regulation, and physiological functions , 2000, Glia.

[37]  M. Nedergaard,et al.  ATP-Mediated Glia Signaling , 2000, The Journal of Neuroscience.

[38]  W. Walz,et al.  Controversy surrounding the existence of discrete functional classes of astrocytes in adult gray matter , 2000, Glia.

[39]  H. Parri,et al.  Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation , 2001, Nature Neuroscience.

[40]  P. Worley,et al.  Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer , 2001, Nature.

[41]  Alan Fine,et al.  Calcium Stores in Hippocampal Synaptic Boutons Mediate Short-Term Plasticity, Store-Operated Ca2+ Entry, and Spontaneous Transmitter Release , 2001, Neuron.

[42]  G. Kollias,et al.  CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity , 2001, Nature Neuroscience.

[43]  M. Iino,et al.  Ca2+‐sensor region of IP3 receptor controls intracellular Ca2+ signaling , 2001 .

[44]  S. Jeftinija,et al.  ATP stimulates calcium‐dependent glutamate release from cultured astrocytes , 2001, Journal of neurochemistry.

[45]  M. Zonta,et al.  Cytosolic Calcium Oscillations in Astrocytes May Regulate Exocytotic Release of Glutamate , 2001, The Journal of Neuroscience.

[46]  V. Matyash,et al.  Requirement of functional ryanodine receptor type 3 for astrocyte migration , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  Clemens Boucsein,et al.  Astrocyte Ca2+ waves trigger responses in microglial cells in brain slices , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[48]  Rafael Yuste,et al.  Calcium oscillations in neocortical astrocytes under epileptiform conditions. , 2002, Journal of neurobiology.

[49]  Eduardo Soriano,et al.  Neuronal Activity Regulates Correlated Network Properties of Spontaneous Calcium Transients in Astrocytes In Situ , 2002, The Journal of Neuroscience.

[50]  S. Oloff,et al.  Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity. , 2002, Journal of neurophysiology.

[51]  M. Götz,et al.  Neuronal or Glial Progeny Regional Differences in Radial Glia Fate , 2003, Neuron.

[52]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[53]  M. Matteoli,et al.  Storage and Release of ATP from Astrocytes in Culture* , 2003, The Journal of Biological Chemistry.

[54]  Eric A Newman,et al.  Glial Cell Inhibition of Neurons by Release of ATP , 2003, The Journal of Neuroscience.

[55]  F. Kirchhoff,et al.  Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus , 2003, The Journal of Neuroscience.

[56]  H. Parri,et al.  The role of Ca2+ in the generation of spontaneous astrocytic Ca2+ oscillations , 2003, Neuroscience.

[57]  B. Ransom,et al.  Functional Hemichannels in Astrocytes: A Novel Mechanism of Glutamate Release , 2003, The Journal of Neuroscience.

[58]  Aaron M. Beedle,et al.  Expression of voltage‐gated Ca2+ channel subtypes in cultured astrocytes , 2003, Glia.

[59]  H. Kettenmann,et al.  Different Mechanisms Promote Astrocyte Ca2+ Waves and Spreading Depression in the Mouse Neocortex , 2003, The Journal of Neuroscience.

[60]  S. Duan,et al.  P2X7 Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes , 2003, The Journal of Neuroscience.

[61]  Andreas Beck,et al.  Calcium release from intracellular stores in rodent astrocytes and neurons in situ. , 2004, Cell calcium.

[62]  V. Gundersen,et al.  Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate , 2004, Nature Neuroscience.

[63]  Todd A Fiacco,et al.  Intracellular Astrocyte Calcium Waves In Situ Increase the Frequency of Spontaneous AMPA Receptor Currents in CA1 Pyramidal Neurons , 2004, The Journal of Neuroscience.

[64]  J. Filosa,et al.  Calcium Dynamics in Cortical Astrocytes and Arterioles During Neurovascular Coupling , 2004, Circulation research.

[65]  Shih-Chun Lin,et al.  Synaptic signaling between neurons and glia , 2004, Glia.

[66]  E. Scemes,et al.  Gap junction channels coordinate the propagation of intercellular Ca2+ signals generated by P2Y receptor activation , 2004, Glia.

[67]  Arnold R. Kriegstein,et al.  Calcium Waves Propagate through Radial Glial Cells and Modulate Proliferation in the Developing Neocortex , 2004, Neuron.

[68]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[69]  P. Navarra,et al.  Electrophysiological and molecular evidence of L‐(Cav1), N‐ (Cav2.2), and R‐ (Cav2.3) type Ca2+ channels in rat cortical astrocytes , 2004, Glia.

[70]  Vladimir Parpura,et al.  Ca2+‐dependent glutamate release involves two classes of endoplasmic reticulum Ca2+ stores in astrocytes , 2004 .

[71]  M. C. Angulo,et al.  Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus , 2004, The Journal of Neuroscience.

[72]  G. Buzsáki,et al.  Calcium Dynamics of Cortical Astrocytic Networks In Vivo , 2004, PLoS biology.

[73]  V. Parpura,et al.  Vesicular Glutamate Transporter-Dependent Glutamate Release from Astrocytes , 2004, Journal of Neuroscience.

[74]  P. Somogyi,et al.  Climbing Fiber Innervation of NG2-Expressing Glia in the Mammalian Cerebellum , 2005, Neuron.

[75]  C. Jahr,et al.  High-Concentration Rapid Transients of Glutamate Mediate Neural-Glial Communication via Ectopic Release , 2005, The Journal of Neuroscience.

[76]  T. Takano,et al.  An astrocytic basis of epilepsy , 2005, Nature Medicine.

[77]  I. Bezprozvanny,et al.  Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region. , 2005, Biophysical journal.

[78]  Eric A Newman,et al.  Calcium Increases in Retinal Glial Cells Evoked by Light-Induced Neuronal Activity , 2005, The Journal of Neuroscience.

[79]  Loredano Pollegioni,et al.  Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[80]  G. Perea,et al.  Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes , 2005, The Journal of Neuroscience.

[81]  Neuronal Synchrony Mediated by Astrocytic Glutamate through Activation of Extrasynaptic NMDA Receptors , 2005, Neuron.

[82]  T. Takano,et al.  Receptor-mediated glutamate release from volume sensitive channels in astrocytes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[83]  M. E. Layton Subtype-selective noncompetitive modulators of metabotropic glutamate receptor subtype 1 (mGluR1). , 2005, Current topics in medicinal chemistry.

[84]  Cathryn L. Kubera,et al.  Astrocytic Purinergic Signaling Coordinates Synaptic Networks , 2005, Science.

[85]  Zhuan Zhou,et al.  “Kiss-and-Run” Glutamate Secretion in Cultured and Freshly Isolated Rat Hippocampal Astrocytes , 2005, The Journal of Neuroscience.

[86]  Maiken Nedergaard,et al.  Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. , 2005, Journal of neurophysiology.

[87]  H. Kettenmann,et al.  Synaptic transmission onto hippocampal glial cells with hGFAP promoter activity , 2005, Journal of Cell Science.

[88]  C. Brosnan,et al.  P2X7 Receptors Mediate ATP Release and Amplification of Astrocytic Intercellular Ca2+ Signaling , 2006, The Journal of Neuroscience.

[89]  Eric A Newman,et al.  Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling , 2006, The Journal of Neuroscience.

[90]  Michela Matteoli,et al.  Synaptobrevin2‐expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis , 2006, The Journal of physiology.

[91]  R. Tsien,et al.  Frequency-Dependent Kinetics and Prevalence of Kiss-and-Run and Reuse at Hippocampal Synapses Studied with Novel Quenching Methods , 2006, Neuron.

[92]  Tullio Pozzan,et al.  Purinergic Receptors Mediate Two Distinct Glutamate Release Pathways in Hippocampal Astrocytes* , 2006, Journal of Biological Chemistry.

[93]  J. Deitmer,et al.  The role of metabotropic glutamate receptors for the generation of calcium oscillations in rat hippocampal astrocytes in situ. , 2006, Cerebral cortex.

[94]  K. McCarthy,et al.  GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS , 2006, Molecular and Cellular Neuroscience.

[95]  H. Murray,et al.  Hypoxia stimulates Ca2+ release from intracellular stores in astrocytes via cyclic ADP ribose-mediated activation of ryanodine receptors. , 2006, Cell calcium.

[96]  H. Kimelberg,et al.  Development of GLAST(+) astrocytes and NG2(+) glia in rat hippocampus CA1: mature astrocytes are electrophysiologically passive. , 2006, Journal of neurophysiology.

[97]  T. Takano,et al.  Astrocyte-mediated control of cerebral blood flow , 2006, Nature Neuroscience.

[98]  Oliver Peters,et al.  Activity-dependent ATP-waves in the mouse neocortex are independent from astrocytic calcium waves. , 2006, Cerebral cortex.