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Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation

Nature Neuroscience volume 4, pages 803–812 (2001)Cite this article

Abstract

Astrocytes respond to chemical, electrical and mechanical stimuli with transient increases in intracellular calcium concentration ([Ca2+]i). We now show that astrocytes in situ display intrinsic [Ca2+]i oscillations that are not driven by neuronal activity. These spontaneous astrocytic oscillations can propagate as waves to neighboring astrocytes and trigger slowly decaying NMDA receptor-mediated inward currents in neurons located along the wave path. These findings show that astrocytes in situ can act as a primary source for generating neuronal activity in the mammalian central nervous system.

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Figure 1: Spontaneous astrocyte activity in the VB thalamus.
Figure 2: Effects of pharmacological agents on spontaneous [Ca2+]i transients.
Figure 3: Spontaneous [Ca2+]i transients in the VB thalamus are localized to astrocytes.
Figure 4: Propagation of spontaneous [Ca2+]i waves within and between astrocytes.
Figure 5: Localized astrocytic activity underlies signaling to neurons.
Figure 6: Astrocyte–neuron signaling is observed under physiological conditions and occurs via NMDA receptors.
Figure 7: Astrocyte–neuron signaling causes a neuronal [Ca2+]i rise.

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References

  1. Cornell-Bell, A. H., Finkbeiner, S. M., Cooper, M. S. & Smith, S. J. Glutamate induces calcium waves in cultured astrocytes: long range glial signaling. Science 247, 470–473 (1990).

    Article  CAS  Google Scholar 

  2. Charles, A. C., Merril, J. E., Ditksen, E. R. & Sanderson, M. J. Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron 6, 983–992 (1991).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Araque, A., Parpura, V., Sanzgiri, R. P. & Haydon, P. G. Glutamate dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurones. Eur. J. Neurosci. 10, 2129–2142 (1998).

    Article  CAS  Google Scholar 

  5. Hassinger, T. D.,. et al. Evidence for glutamate-mediated activation of hippocampal neurons by glial calcium waves. J. Neurobiol. 28, 159–170 (1995).

    Article  CAS  Google Scholar 

  6. Charles, A. C. Glia–neuron intercellular Ca2+ signaling. Dev. Neurosci. 16, 196–206 (1994).

    Article  CAS  Google Scholar 

  7. Nedergaard, M. Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263, 1768–1771 (1994).

    Article  CAS  Google Scholar 

  8. Newman, E. A. & Zahs, K. R. Modulation of neuronal activity by glial cells in the retina. J. Neurosci. 18, 4022–4028 (1998).

    Article  CAS  Google Scholar 

  9. Kang, J., Jiang, L., Goldman, S. A. & Nedergaard, M. Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat. Neurosci. 1, 683–692 (1998).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Parpura, V., Basarsky, T. A., Liu, F., Jeftinija, K. & Haydon P. G. Glutamate-mediated astrocyte–neuron signaling. Nature 369, 744–747 (1994).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Innocenti, B., Parpura, V. & Haydon P. G. Imaging extracellular waves of glutamate during calcium signaling in cultured astrocytes. J. Neurosci. 20, 1800–1808 (2000).

    Article  CAS  Google Scholar 

  14. Araque, A., Li, N., Doyle, R. T. & Haydon, P. G. Snare protein dependent glutamate release from astrocytes. J. Neurosci. 20, 666–673 (2000).

    Article  CAS  Google Scholar 

  15. Araque, A., Parpura, V., Sanzgiri, R. P. & Haydon, P. G. Tripartite synapse: glia the unacknowledged partner. Trends Neurosci. 22, 208–215 (1999).

    Article  CAS  Google Scholar 

  16. Carmignoto, G. Reciprocal communication systems between astrocytes and neurons. Prog. Neurobiol. 62, 561–581 (2000).

    Article  CAS  Google Scholar 

  17. Schnitzer, J., Franke, W. W. & Schachner, M. Immunocytochemical demonstration of vimentin in astrocytes and ependymal cells of developing and adult mouse nervous system. J. Cell. Biol. 90, 435–447 (1981).

    Article  CAS  Google Scholar 

  18. Giaume, C. & Venance, L. Intercellular calcium signaling and gap junctional communication in astrocytes. Glia 24, 50–64 (1998).

    Article  CAS  Google Scholar 

  19. Finkbeiner, S. M. Glial calcium. Glia 9, 83–104 (1993).

    Article  CAS  Google Scholar 

  20. Guthrie, P. B. et al. ATP released from astrocytes mediates glial calcium waves. J. Neurosci. 19, 520–528 (1999).

    Article  CAS  Google Scholar 

  21. Parri, H. R. & Crunelli, V. Sodium current in thalamocortical neurons: role of a non-inactivating component in tonic and burst firing. J. Neurosci. 18, 854–867 (1998).

    Article  CAS  Google Scholar 

  22. Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B. & Seeburg, P. H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540 (1994).

    Article  CAS  Google Scholar 

  23. Wyllie, D. J. A., Behe, B. & Colquhoun D. Single-channel activation and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors. J. Physiol. (Lond.) 510, 1–18 (1998).

    Article  CAS  Google Scholar 

  24. Wenzel, A., Villa, M., Mohler, H. & Benke, D. Developmental and regional expression of NMDA receptor subtypes containing the NR2D subunit in rat brain. J. Neurochem. 66, 1240–1247 (1996).

    Article  CAS  Google Scholar 

  25. Yuste, R., Peinado, A. & Katz, L. C. Neuronal domains in developing neocortex. Science 257, 665–669 (1992).

    Article  CAS  Google Scholar 

  26. Porter, J. T. & Mccarthy, K. D. GFAP positive hippocampal astrocytes in situ respond to glutamatergic neuroligands with increases in [Ca]i . Glia 13, 101–112 (1995).

    Article  CAS  Google Scholar 

  27. Araque, A., Sanzgiri, R. P., Parpura, V. & Haydon, P. G. Calcium elevation in astrocytes causes an NMDA receptor dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J. Neurosci. 18, 6822–6829 (1998).

    Article  CAS  Google Scholar 

  28. Spreafico, R. et al. Distribution of AMPA selective glutamate receptors in the thalamus of adult rats and during postnatal development. A light and ultrastructural immunocytochemical study. Brain Res. Dev. Brain Res. 82, 231–244 (1994).

    Article  CAS  Google Scholar 

  29. Golshani, P., Warren, R. A. & Jones, E. G. Progression of change in NMDA, non-NMDA and metabotropic glutamate receptor function at the developing corticothalamic synapse. J. Neurophysiol. 80, 143–154 (1998).

    Article  CAS  Google Scholar 

  30. Misra, S. C., Brickley, S. G., Wyllie, D. J. & Cull-Candy, S. G. Slow deactivation kinetics of NMDA receptors containing NR1 and NR2D subunits in rat cerebellar purkinje cells. J. Physiol. (Lond.) 525, 299–305 (2000).

    Article  CAS  Google Scholar 

  31. Emptage, N. J, Reid., C. A. & Fine, A. Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store operated calcium entry and spontaneous transmitter release. Neuron 29, 197–208 (20 01).

  32. Gu, X. & Spitzer, N. C. Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients. Nature 375, 784–787 (1995).

    Article  CAS  Google Scholar 

  33. Yuste, R., Nelson, D. A., Rubin, W. W. & Katz, L. C. Neuronal domains in developing neocortex: mechanisms of coactivation. Neuron 14, 7–17 (1995).

    Article  CAS  Google Scholar 

  34. Goodman, C. S. & Shatz, C. J. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72S, 77–98 (1993).

    Article  Google Scholar 

  35. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).

    Article  CAS  Google Scholar 

  36. Catalano, S. M. & Shatz C. J. Activity-dependent cortical target selection by thalamic axons. Science 281, 559–562 (1998).

    Article  CAS  Google Scholar 

  37. Miller, B., Chou, L. & Finlay, B. L. The early development of thalamocortical and corticothalamic projections. J. Comp. Neurol. 335, 16–41 (1993).

    Article  CAS  Google Scholar 

  38. Liu, X. B., Honda, C. N. & Jones, E. G. Distribution of four types of synapse on physiologically identified relay neurons in the ventral posterior thalamic nucleus of the cat. J. Comp. Neurol. 352, 69–91 (1995).

    Article  CAS  Google Scholar 

  39. Zantua, J. B., Wasserstrom, S. P., Arends, J. J. A., Jacquin, M. F. & Woolsey, T. A. Postnatal development of mouse “whisker” thalamus: ventroposterior medial nucleus (VPM), barreloids, and their thalamocortical relay neurons. Somatosens. Motor Res. 13, 307–322 (1996).

    Article  CAS  Google Scholar 

  40. Rajan, I. & Cline, H. T. Glutamate receptor activity is required for normal development of tectal cell dendrites in vivo. J. Neurosci. 18, 7836–7846 (1998).

    Article  CAS  Google Scholar 

  41. Collingridge, G. C. & Bliss, T.V. Memories of NMDA receptors and LTP. Trends Neurosci. 18, 54–56 (1995).

    Article  CAS  Google Scholar 

  42. Berridge, M. J. Neuronal calcium signaling. Neuron 21, 13–26 (1998).

    Article  CAS  Google Scholar 

  43. Perkel, D. J., Petrozzino, J. J., Nicoll, R. A. & Connor, J. A. The role of Ca2+ entry via synaptically activated NMDA receptors in the induction of long term potentiation. Neuron 11, 817–823 (1993).

    Article  CAS  Google Scholar 

  44. Silver, J., Lopez, S. E., Wahlsten, D. & Coughlin, J. Axonal guidance during development of the great cerebral commisures, descriptive and experimental studies in vivo on the role of preformed glial pathways. J. Comp. Neurol. 210, 10–29 (1982).

    Article  CAS  Google Scholar 

  45. Rakic, P., Cameron, R. S. & Komuro, H. Recognition adhesion, transmembrane signaling and cell motility in guided neuronal migration. Curr. Opin. Neurobiol. 4, 63–69 (1994).

    Article  CAS  Google Scholar 

  46. Lois, C., Garcia-Verdugo, J.-M. & Alvarez-Buylla, A. Chain migration of neuronal precursors. Science 271, 978–981 (1996).

    Article  CAS  Google Scholar 

  47. Turner, J. P., Leresche, N., Guyon, A., Soltesz, I. & Crunelli, V. Sensory input and burst firing output of rat and cat thalamocortical cells: the role of NMDA and non-NMDA receptors. J. Physiol. (Lond.) 480, 281–295 (1994).

    Article  CAS  Google Scholar 

  48. Perez Velazquez, J. L. & Carlen, P. L. Development of firing patterns and electrical properties in neurons of the rat ventrobasal thalamus. Dev. Brain. Res. 91, 164–170 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank S.W. Hughes and T.I. Tóth for data analysis and the development of specialized statistical analysis software, and V.H. Perry for assistance with the immunocytochemistry analysis. The work was supported by the Wellcome Trust (grant 37089–98).

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  1. School of Biosciences, Cardiff University, Museum Avenue, PO Box 911, Cardiff, CF10 3US, Wales, UK

    H. Rheinallt Parri, Timothy M. Gould & Vincenzo Crunelli

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Correspondence to Vincenzo Crunelli.

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Parri, H., Gould, T. & Crunelli, V. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci 4, 803–812 (2001). https://doi.org/10.1038/90507

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