Trends in Neurosciences
Volume 26, Issue 10, October 2003, Pages 531-535
Journal home page for Trends in Neurosciences

New roles for astrocytes: Regulation of CNS synaptogenesis

https://doi.org/10.1016/j.tins.2003.08.005Get rights and content

Abstract

The notion that astrocytes have a profound influence on the function of synapses between CNS neurons implies that the development of synaptic connections and their glial neighbors are controlled by reciprocally acting signals. Currently, however, synaptogenesis is considered a purely neuronal affair. This article summarizes recent experimental evidence suggesting that this may not be the case. Astrocytes may indeed regulate the formation, maturation and maintenance of synapses. The recent advances caution that synapses cannot develop correctly without astrocytes. Further progress on this issue requires new experimental models to identify signaling pathways and to scrutinize the relevance of glia–synapse interactions in vivo.

Section snippets

Astrocytes control synapse number

The idea that astrocytes play a role in the formation of synaptic contacts arises from a conspicuous temporal correlation between synaptogenesis and the differentiation of this glial cell type [20] (Figure 2). In rodents, for example, astrocytes are generated around birth, whereas massive synaptogenesis starts at the end of the first postnatal week and continues for two-to-three weeks 20, 21. The long duration of synaptogenesis contrasts with the notion that individual synaptic contacts are

Astrocytes help synapses to grow up

During the maturation phase, synaptic connections acquire their characteristic transmission properties. This involves changes in the number of vesicles in presynaptic terminals, and changes in the composition of the exocytosis machinery and the postsynaptic receptor complex 9, 43, 44 (Figure 1). The studies on purified RGCs mentioned in the preceding section showed that glial cells enhance the size of miniature postsynaptic currents 30, 32, 33 and that this effect is mediated, at least in part,

Astrocytes determine the fate of synapses

During brain development, only some of the newly formed synapses are strengthened and maintained, whereas all others are eliminated 9, 18, 58 (Figure 1). Do astrocytes help to maintain synapses? There is little experimental evidence for such an effect. Ablation of astrocytes in vivo causes loss of connections [59] but this could be a consequence, rather than the cause, of massive neurodegeneration. Barres and colleagues [33] reported that removal of astrocytic feeding layers from cultured RGCs

Concluding remarks

Astrocytes possibly contribute to several stages of synapse development in the CNS. The hypotheses presented here rely mainly on studies using culture preparations; the molecular mechanisms of these interactions are still largely unknown. Progress in this area depends on three issues. First, the astrocyte-derived signals that control synapse development must be identified. This requires new preparations, where neurons from the postnatal CNS can be studied in the absence and presence of glial

Acknowledgements

Research in our laboratory is supported by the Centre Nationale de la Recherche Scientifique, the Max-Planck-Gesellschaft, the Fondation Pour La Recherche Medicale, the Fondation Electricité de France, the Ara Parseghian Medical Research Foundation, the Region Alsace, and the Deutsche Forschungsgemeinschaft.

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