Trends in Neurosciences
Volume 19, Issue 8, August 1996, Pages 339-345
Journal home page for Trends in Neurosciences

News on glutamate receptors in glial cells

https://doi.org/10.1016/0166-2236(96)10043-6Get rights and content

Abstract

Glutamate (Glu) receptors convey most of the excitatory synaptic transmission in the mammalian CNS. Distinct Glu-receptor genes and different subtypes of glutamate-activated channels are expressed ubiquitously throughout the developing and mature brain in the two major macroglial cell types, astrocytes and oligodendrocytes. These glial receptors are found in acutely isolated cells and in brain slices, and are therefore functional in vivo. Glutamate receptors in glial cells are activated during neuronal activity, and their activation modulates gene expression in astrocytes and oligodendrocytes. The proliferation and differentiation of glial precursor cells are also regulated by activation of Glu receptors, suggesting that the excitatory transmitter might be one of the environmental signals that regulate glial-cell development. Trends Neurosci. (1996) 19, 339–345

Section snippets

Molecular biology and functional properties of glutamate receptors

Based on their pharmacological and electrophysiological properties, iGlu receptors have been subdivided into three subtypes: AMPA, kainate and NMDA receptors. These receptors contain integral cationic ion channels that are associated with the ligand binding site. Unlike iGlu receptors, mGlu receptors are coupled to G proteins regulating either inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-mediated release of intracellular Ca2+, or inhibition of intracellular cAMP production. Molecular cloning and

Physiological properties of ionotropic glutamate receptors

A variety of native iGlu receptors and mGlu receptors have been characterized in glia in situ or in freshly isolated cells (Table 1). Glial cells in the corpus callosum24, 25, Bergmann glial cells in the cerebellum[26], and astrocytes in the hippocampus28, 29, 30, 31, 33express receptors with functional and pharmacological properties of the AMPA subtype. These in situ studies have shown that glutamate and kainate not only activated a cationic receptor conductance, but also significantly reduced

Properties of glial glutamate receptors in vitro

The functional properties of iGlu receptors and mGlu receptors have been analysed in different glial cell types in vitro. Expression of iGlu receptors has been consistently demonstrated in all macroglial cells, but mGlu receptors appear to be expressed only in astrocytes60, 61, 62, 63(however, see Ref. [64]). Molecular, electrophysiological and biophysical studies in cultured cells confirmed that glial and neuronal iGlu receptors are made up of the same subunits with similar functional

Concluding remarks

Millimolar concentrations of glutamate are released from axons and presynaptic terminals during and after the propagation of action potentials95, 96, 97. The cytoarchitectural arrangement of the two major macroglial cell types in the brain implies that neuronal glutamate-dependent signals can directly activate glial receptors. Astrocytes are in the position to sense synaptic activity at their processes that interdigitate with nerve endings. Oligodendrocytes, on the other hand, can respond to

Future directions

The complete understanding of the physiological role of Glu receptors in glia is most definitely a challenge for the future. It is still unclear whether these and other neurotransmitter receptors perform specific tasks in distinct macroglial cell types during CNS development and in the mature brain. The question of whether glial Glu receptors are indeed activated in situ during neural activity is also unanswered. If this is the case, are there specific patterns of activation that result in

Acknowledgements

CS acknowledges grants from the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, the Sandoz Foundation, and the Fonds der Chemischen Industrie. We thank Mario Pende for the data presented in Fig. 4, Klaus Kressin for assistance with Fig. 5, and Chris McBain and Mario Pende for critically reading the manuscript.

References (99)

  • B. Bettler et al.

    Neuropharmacology

    (1995)
  • J-P. Pin et al.

    Neuropharmacology

    (1995)
  • K.M. Partin

    Neuron

    (1993)
  • M. Hollmann et al.

    Neuron

    (1994)
  • J.A. Bennett et al.

    Neuron

    (1995)
  • P. Jonas

    Neuron

    (1994)
  • P. Bochet

    Neuron

    (1994)
  • J.R.P. Geiger

    Neuron

    (1995)
  • N. Burnashev

    Neuron

    (1992)
  • B.A. Barres

    Neuron

    (1990)
  • E.A. Schwartz

    Neuron

    (1993)
  • L.J. Martin

    Neuroscience

    (1993)
  • K. Sato et al.

    Neuroscience

    (1993)
  • N.C. Day

    Mol. Brain Res.

    (1995)
  • J.E. Huettner

    Neuron

    (1990)
  • D.K. Patneau

    Neuron

    (1994)
  • Y. Tanabe

    Neuron

    (1992)
  • M.V. Catania

    Neuroscience

    (1994)
  • M. Fotuhi

    Mol. Brain Res.

    (1994)
  • B. Pearce

    Neurosci. Lett.

    (1986)
  • R.B. Puchalski

    Neuron

    (1994)
  • H. Sontheimer

    Neuron

    (1989)
  • R.D. McKinnon

    Neuron

    (1990)
  • M.C. Raff et al.

    Cell

    (1985)
  • S. Temple et al.

    Cell

    (1986)
  • J.J. LoTurco

    Neuron

    (1995)
  • P. Shrager et al.

    Dev. Brain Res.

    (1995)
  • K.J. Mack

    Mol. Brain Res.

    (1994)
  • D. Weinreich et al.

    Brain Res.

    (1975)
  • J.F. Lauder

    Trends Neurosci.

    (1993)
  • S. Nakanishi

    Science

    (1992)
  • M. Hollmann et al.

    Annu. Rev. Neurosci.

    (1994)
  • K.A. Yamada et al.

    J. Neurosci.

    (1993)
  • C.J. McBain et al.

    Physiol. Rev.

    (1994)
  • N.J. Sucher

    J. Neurosci.

    (1995)
  • A.M. Ciabarra

    J. Neurosci.

    (1995)
  • V. Gallo

    J. Neurosci.

    (1992)
  • Z.G. Wo et al.

    Proc. Natl. Acad. Sci. U. S. A.

    (1994)
  • N. Burnashev

    Science

    (1992)
  • M. Hollmann et al.

    Science

    (1991)
  • T. Verdoorn

    Science

    (1991)
  • R.I. Hume et al.

    Science

    (1991)
  • N. Burnashev

    Science

    (1992)
  • H. Mori

    Nature

    (1992)
  • T. Berger

    J. Neurosci. Res.

    (1992)
  • T. Berger

    Glia

    (1995)
  • T. Müller

    Science

    (1992)
  • T. Müller

    NeuroReport

    (1993)
  • C. Steinhäuser et al.

    Hippocampus

    (1994)
  • Cited by (308)

    • Epigenetics in child psychiatry

      2021, Epigenetics in Psychiatry
    • Glia plasma membrane transporters: Key players in glutamatergic neurotransmission

      2016, Neurochemistry International
      Citation Excerpt :

      This lower glia concentration can be due to the presence of glutamine synthetase (GS), an enzyme that converts Glu to Gln as part of the recycling of Glu released from the neuron (McKenna, 2007) (Fig. 2). It is now well accepted that Glu responses are mediated by receptors and transporters, which are expressed in neurons and glial cells (Steinhauser and Gallo, 1996) as well as in other non-nervous system cells (Patton et al., 1998). Glutamatergic receptors have been divided into two groups according to their signaling properties in: ionotropic (GRI) and metabotropic (GRM) Glu receptors.

    • Excitotoxicity and the Kynurenine Pathway in Multiple Sclerosis

      2023, Handbook of Neurotoxicity, Second Edition
    View all citing articles on Scopus
    View full text