Review
Role of glia in synapse development

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Abstract

Recent studies suggest that glial cells regulate certain aspects of synapse development. Neurons can form synapses without glia, but may require glia-derived cholesterol to form numerous and efficient synapses. During synapse maturation, soluble and contact-dependent factors from glia may influence the composition of the postsynaptic density. Finally, synaptic connections appear to require glia to support their structural stability. Given the new evidence, it may be time now to acknowledge glia as a source for synaptogenesis-promoting signals. Scrutinizing the molecular mechanisms underlying this new function of glia and testing its relevance in vivo may help to understand how synapses develop and why they degenerate under pathological conditions.

Introduction

Views on the liaison between synapses and glial cells have changed within the last few years, with once avantgardistic opinions on glial function [1] gaining a foothold in mainstream neuroscience 2., 3., 4., 5., 6.. Until recently, synaptogenesis has been regarded as a purely neuronal affair. Here, I summarize new evidence that glia-derived signals control the extent of synapse formation, induce postsynaptic maturation processes and help to maintain synaptic stability. Updates on aspects of neuron–glia interactions beyond the scope of this article can be found elsewhere 7., 8., 9., 10., 11., 12., 13., 14., 15., 16..

Section snippets

Synaptic birth control by glia

Within the last years, our understanding of how neurons establish synaptic connections has greatly expanded. Genetic, biochemical and cell culture screens as well as advanced imaging techniques revealed new cellular components and mechanisms that are involved in this fundamental process (reviewed in 17., 18., 19., 20., 21., 22., 23., 24.). A still unresolved question is, however, whether neurons form synapses autonomously or whether they require external signals. A possible source of such

Glia help synapses to mature

Newborn synapses undergo a maturation process, which endows each connection with its specific transmission properties. Recent work indicates that glia-derived signals regulate the maturation of the postsynaptic density (PSD). The aforementioned studies on purified RGCs showed that glial cells enhance the quantal size, which represents the magnitude of postsynaptic responses to individual quanta of transmitter 34., 35••., 36••.. In principle, this result can stem from a higher intravesicular

Glia live and let die synapses

There is increasing evidence that individual synaptic connections have an intrinsic lifetime 61•., 62., 63., which is modulated by electrical activity and probably other, still largely unknown factors (for recent reviews see 25., 64., 65.). Several papers suggest that glial cells may control synaptic stability and participate in their elimination. The pioneering work of Trachtenberg and Thompson [66] showed that, in young rats, withdrawal of the Schwann cells that cover NMJs, also called

Conclusions

Taken together, the results summarized above shed new light on the synapse–glia affair. The establishment of a synaptic contact probably relies on neuronal signals, but the massive increase in synapse number and the diverse presynaptic and postsynaptic maturation processes appear to require glia-derived components. Notably, the various types of synapses may differ in their reliance on glial components. Clearly, the next step is to define the molecular details of these interactions and to

Acknowledgements

I thank D Dalencon for help with the literature search and BA Barres and M Muzet for reading this manuscript. Research in my laboratory is supported by the Centre National de la Recherche Scientifique, the Max-Planck-Gesellschaft, the Fondation pour la Recherche Medicale, the Fondation Electricité de France and the Ara-Parseghian Medical Research Foundation. I apologize to those colleagues whose studies I could not cite due to topic restrictions.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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