Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-08T06:29:24.898Z Has data issue: false hasContentIssue false
  • English
  • Français

Regulation of microglia by ionotropic glutamatergic and GABAergic neurotransmission

Published online by Cambridge University Press:  14 December 2011

Wai T. Wong ,
Minhua Wang  and
Wei Li
Wai T. Wong*
Affiliation:
Unit on Neuron–Glia Interactions in Retinal Diseases, National Eye Institute, National Institute of Health, Bethesda, MD, USA
Minhua Wang
Affiliation:
Unit on Neuron–Glia Interactions in Retinal Diseases, National Eye Institute, National Institute of Health, Bethesda, MD, USA
Wei Li
Affiliation:
Unit on Retinal Neurophysiology, National Eye Institute, National Institute of Health, Bethesda, MD, USA
*
Correspondence should be addressed to: Wai T. Wong, National Eye Institute, National Institute of Health, 6 Center Drive, Room 217 Bethesda, MD 20892, USA phone: +1 301 496 1758 fax: +1 301 496 1759 email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Recent studies have indicated that constitutive functions of microglia in the healthy adult central nervous system (CNS) involve immune surveillance, synapse maintenance and trophic support. These functions have been related to the ramified structure of ‘resting’ microglia and the prominent motility in their processes that provide extensive coverage of the entire extracellular milleu. In this review, we examine how external signals, and in particular, ionotropic neurotransmission, regulate features of microglial morphology and process motility. Current findings indicate that microglial physiology in the healthy CNS is constitutively and reciprocally regulated by endogenous ionotropic glutamatergic and GABAergic neurotransmission. These influences do not act directly on microglial cells but indirectly via the activity-dependent release of ATP, likely through a mechanism involving pannexin channels. Microglia in the ‘resting’ state are not only dynamically active, but also constantly engaged in ongoing communication with neuronal and macroglial components of the CNS in a functionally relevant way.

Keywords

Microglial motilitypurinergic transmissionATPpannexin channelsneuronal activity
Type
Research Article
Information
Neuron Glia Biology , Volume 7 , Special Issue 1: The Physiological Function of Microglia , February 2011 , pp. 41 - 46
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bao, L., Locovei, S. and Dahl, G. (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Letters 572, 65–68.CrossRefGoogle ScholarPubMed
Bruzzone, R., Barbe, M.T., Jakob, N.J. and Monyer, H. (2005) Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes. Journal of Neurochemistry 92, 1033–1043.CrossRefGoogle ScholarPubMed
Butt, A.M. (2011) ATP: a ubiquitous gliotransmitter integrating neuron–glial networks. Seminars in Cell and Developmental Biology 22, 205–213.CrossRefGoogle ScholarPubMed
Chen, T., Koga, K., Li, X.Y. and Zhuo, M. (2010) Spinal microglial motility is independent of neuronal activity and plasticity in adult mice. Molecular Pain 6, 19.CrossRefGoogle ScholarPubMed
Cheung, G., Kann, O., Kohsaka, S., Faerber, K. and Kettenmann, H. (2009) GABAergic activities enhance macrophage inflammatory protein-1alpha release from microglia (brain macrophages) in postnatal mouse brain. The Journal of Physiology 587, 753–768.CrossRefGoogle ScholarPubMed
Chu, Y., Jin, X., Parada, I., Pesic, A., Stevens, B., Barres, B. et al. (2011) Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proceedings of the National Academy of Sciences of the U.S.A. 107, 7975–7980.CrossRefGoogle Scholar
Cotrina, M.L., Lin, J.H., Alves-Rodrigues, A., Liu, S., Li, J., Azmi-Ghadimi, H. et al. (1998) Connexins regulate calcium signaling by controlling ATP release. Proceedings of the National Academy of Sciences of the U.S.A. 95, 15735–15740.CrossRefGoogle ScholarPubMed
Dahl, G. and Locovei, S. (2006) Pannexin: to gap or not to gap, is that a question? IUBMB Life 58, 409–419.CrossRefGoogle ScholarPubMed
Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S. et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 8, 752–758.CrossRefGoogle ScholarPubMed
Dibaj, P., Steffens, H., Nadrigny, F., Neusch, C., Kirchhoff, F. and Schomburg, E.D. (2010) Long-lasting post-mortem activity of spinal microglia in situ in mice. Journal of Neuroscience Research 88, 2431–2440.CrossRefGoogle ScholarPubMed
Dibaj, P., Steffens, H., Zschuntzsch, J., Nadrigny, F., Schomburg, E.D., Kirchhoff, F. et al. (2011) In vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS. PLoS One 6, e17910.Google Scholar
Elkabes, S., DiCicco-Bloom, E.M. and Black, I.B. (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. Journal of Neuroscience 16, 2508–2521.CrossRefGoogle ScholarPubMed
Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R.M., Curti, A., Idzko, M. et al. (2006) The P2X7 receptor: a key player in IL-1 processing and release. Journal of Immunology 176, 3877–3883.Google Scholar
Fontainhas, A.M., Wang, M., Liang, K.J., Chen, S., Mettu, P., Damani, M. et al. (2011) Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS One 6, e15973.CrossRefGoogle ScholarPubMed
Gottlieb, M. and Matute, C. (1997) Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. Journal of Cerebral Blood Flow and Metabolism 17, 290–300.CrossRefGoogle ScholarPubMed
Graeber, M.B. (2010) Changing face of microglia. Science 330, 783–788.CrossRefGoogle ScholarPubMed
Hagino, Y., Kariura, Y., Manago, Y., Amano, T., Wang, B., Sekiguchi, M. et al. (2004) Heterogeneity and potentiation of AMPA type of glutamate receptors in rat cultured microglia. Glia 47, 68–77.Google Scholar
Harada, T., Harada, C., Kohsaka, S., Wada, E., Yoshida, K., Ohno, S. et al. (2002) Microglia–Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. Journal of Neuroscience 22, 9228–9236.CrossRefGoogle ScholarPubMed
Honda, S., Sasaki, Y., Ohsawa, K., Imai, Y., Nakamura, Y., Inoue, K. et al. (2001) Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. Journal of Neuroscience 21, 1975–1982.CrossRefGoogle ScholarPubMed
Hume, D.A., Perry, V.H. and Gordon, S. (1983) Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers. Journal of Cell Biology 97, 253–257.CrossRefGoogle Scholar
Iglesias, R., Dahl, G., Qiu, F., Spray, D.C. and Scemes, E. (2009) Pannexin 1: the molecular substrate of astrocyte ‘hemichannels’. Journal of Neuroscience 29, 7092–7097.CrossRefGoogle ScholarPubMed
Kettenmann, H., Hanisch, U.K., Noda, M. and Verkhratsky, A. (2011) Physiology of microglia. Physiological Reviews 91, 461–553.CrossRefGoogle ScholarPubMed
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M. et al. (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446, 1091–1095.CrossRefGoogle ScholarPubMed
Kurth-Nelson, Z.L., Mishra, A. and Newman, E.A. (2009) Spontaneous glial calcium waves in the retina develop over early adulthood. Journal of Neuroscience 29, 11339–11346.Google Scholar
Lee, J.E., Liang, K.J., Fariss, R.N. and Wong, W.T. (2008) Ex vivo dynamic imaging of retinal microglia using time-lapse confocal microscopy. Investigative Ophthalmology and Visual Science 49, 4169–4176.Google Scholar
Lee, M., Schwab, C. and McGeer, P.L. (2011) Astrocytes are GABAergic cells that modulate microglial activity. Glia 59, 152–165.CrossRefGoogle ScholarPubMed
Liang, K.J., Lee, J.E., Wang, Y.D., Ma, W., Fontainhas, A.M., Fariss, R.N. et al. (2009) Regulation of dynamic behavior of retinal microglia by CX3CR1 signaling. Investigative Ophthalmology and Visual Science 50, 4444–4451.CrossRefGoogle ScholarPubMed
Liu, G.J., Nagarajah, R., Banati, R.B. and Bennett, M.R. (2009) Glutamate induces directed chemotaxis of microglia. European Journal of Neuroscience 29, 1108–1118.CrossRefGoogle ScholarPubMed
Locovei, S., Wang, J. and Dahl, G. (2006) Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Letters 580, 239–244.CrossRefGoogle ScholarPubMed
Luchetti, S., Huitinga, I. and Swaab, D.F. (2011) Neurosteroid and GABA-A receptor alterations in Alzheimer's disease, Parkinson's disease and multiple sclerosis. Neuroscience 191, 6–21.Google Scholar
Newman, E.A. (2004) Glial modulation of synaptic transmission in the retina. Glia 47, 268–274.Google Scholar
Nimmerjahn, A., Kirchhoff, F. and Helmchen, F. (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318.CrossRefGoogle ScholarPubMed
Noda, M., Nakanishi, H., Nabekura, J. and Akaike, N. (2000) AMPA-kainate subtypes of glutamate receptor in rat cerebral microglia. Journal of Neuroscience 20, 251–258.CrossRefGoogle ScholarPubMed
Ohsawa, K. and Kohsaka, S. (2011) Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brain. Glia. 59, 1793–1799.CrossRefGoogle ScholarPubMed
Pankratov, Y., Lalo, U., Verkhratsky, A. and North, R.A. (2006) Vesicular release of ATP at central synapses. Pflugers Archiv 452, 589–597.Google Scholar
Paolicelli, R.C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P. et al. (2011) Synaptic pruning by microglia is necessary for normal brain development. Science. 333, 1456–1458.CrossRefGoogle ScholarPubMed
Perry, V.H., Nicoll, J.A. and Holmes, C. (2010) Microglia in neurodegenerative disease. Nature Reviews Neurology 6, 193–201.CrossRefGoogle ScholarPubMed
Pocock, J.M. and Kettenmann, H. (2007) Neurotransmitter receptors on microglia. Trends in Neurosciences 30, 527–535.CrossRefGoogle ScholarPubMed
Raivich, G. (2005) Like cops on the beat: the active role of resting microglia. Trends in Neurosciences 28, 571–573.CrossRefGoogle ScholarPubMed
Ransohoff, R.M. and Cardona, A.E. (2011) The myeloid cells of the central nervous system parenchyma. Nature 468, 253–262.CrossRefGoogle Scholar
Samuels, S.E., Lipitz, J.B., Dahl, G. and Muller, K.J. (2010) Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury. Journal of General Physiology 136, 425–442.Google Scholar
Santos, A.M., Calvente, R., Tassi, M., Carrasco, M.C., Martin-Oliva, D., Marin-Teva, J.L. et al. (2008) Embryonic and postnatal development of microglial cells in the mouse retina. Journal of Comparative Neurology 506, 224–239.Google Scholar
Schaeffer, E.L. and Gattaz, W.F. (2008) Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology 198, 1–27.CrossRefGoogle ScholarPubMed
Silverman, W., Locovei, S. and Dahl, G. (2008) Probenecid, a gout remedy, inhibits pannexin 1 channels. American Journal of Physiology. Cell Physiology 295, C761–C767.CrossRefGoogle ScholarPubMed
Stellwagen, D. and Malenka, R.C. (2006) Synaptic scaling mediated by glial TNF-alpha. Nature 440, 1054–1059.Google Scholar
Stevens, B., Allen, N.J., Vazquez, L.E., Howell, G.R., Christopherson, K.S., Nouri, N. et al. (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131, 1164–1178.CrossRefGoogle ScholarPubMed
Stout, C.E., Costantin, J.L., Naus, C.C. and Charles, A.C. (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. Journal of Biological Chemistry 277, 10482–10488.CrossRefGoogle ScholarPubMed
Streit, W.J. (2001) Microglia and macrophages in the developing CNS. Neurotoxicology 22, 619–624.Google Scholar
Streit, W.J., Braak, H., Xue, Q.S. and Bechmann, I. (2009) Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathologica 118, 475–485.Google Scholar
Tremblay, M.E., Lowery, R.L. and Majewska, A.K. (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biology 8, e1000527.Google Scholar
Verderio, C. and Matteoli, M. (2011) ATP in neuron–glia bidirectional signalling. Brain Research Reviews 66, 106–114.Google Scholar
Wake, H., Moorhouse, A.J., Jinno, S., Kohsaka, S. and Nabekura, J. (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. Journal of Neuroscience 29, 3974–3980.Google Scholar
Wong, R.O. (1999) Retinal waves and visual system development. Annual Review of Neuroscience 22, 29–47.Google Scholar
Wong, W.T., Myhr, K.L., Miller, E.D. and Wong, R.O. (2000) Developmental changes in the neurotransmitter regulation of correlated spontaneous retinal activity. Journal of Neuroscience 20, 351–360.Google Scholar
Wu, L.J. and Zhuo, M. (2008) Resting microglial motility is independent of synaptic plasticity in mammalian brain. Journal of Neurophysiology 99, 2026–2032.CrossRefGoogle ScholarPubMed
Xiang, Z., Chen, M., Ping, J., Dunn, P., Lv, J., Jiao, B. et al. (2006) Microglial morphology and its transformation after challenge by extracellular ATP in vitro. Journal of Neuroscience Research 83, 91–101.Google Scholar
Yamada, J., Sawada, M. and Nakanishi, H. (2006) Cell cycle-dependent regulation of kainate-induced inward currents in microglia. Biochemical and Biophysical Research Communications 349, 913–919.Google Scholar