Trends in Neurosciences
New roles for astrocytes: Regulation of CNS synaptogenesis
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.
References (69)
Glial cells as active partners in synaptic functions
Prog. Brain Res.
(2001)Tripartite synapses: glia, the unacknowledged partner
Trends Neurosci.
(1999)- et al.
Visualizing synapse formation and remodeling: recent advances in real-time imaging of CNS synapses
Neurosci. Res.
(2001) Synaptogenesis: insights from worm and fly
Curr. Opin. Neurobiol.
(2002)- et al.
Activity-dependent synaptogenesis in the adult mammalian cortex
Neuron
(2002) Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions
Trends Neurosci.
(1996)- et al.
New views on synapse–glia interactions
Curr. Opin. Neurobiol.
(1996) - et al.
Molecular mechanisms controlling cortical gliogenesis
Curr. Opin. Neurobiol.
(2002) Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment
Neuron
(2000)Neurons generated from adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in vitro
Exp. Neurol.
(2000)
Role of glia-derived cholesterol in synaptogenesis: new revelations in the synapse–glia affair
J. Physiol. (Paris)
Role of cholesterol in synapse formation and function
Biochim. Biophys. Acta
Lipid rafts in neuronal signaling and function
Trends Neurosci.
Proteomic analysis of astrocytic secretion in the mouse. Comparison with the cerebrospinal fluid proteome
J. Biol. Chem.
Regulation of agrin expression in hippocampal neurons by cell contact and electrical activity
Brain Res. Mol. Brain Res.
Organizing principles of the axoglial apparatus
Neuron
Developmental clustering of ion channels at and near the node of Ranvier
Dev. Biol.
Development of nodes of Ranvier
Curr. Opin. Neurobiol.
Glutamate uptake
Prog. Neurobiol.
Activity-dependent editing of neuromuscular synaptic connections
Brain Res. Bull.
Schwann cell-induced loss of synapses in the central nervous system
Brain Res.
Maternity leads to morphological synaptic plasticity in the oxytocin system
Prog. Brain Res.
Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function
Neuron
Dynamic signaling between astrocytes and neurons
Annu. Rev. Physiol.
New insights into neuron–glia communication
Science
Functional consequences of morphological neuroglial changes in the magnocellular nuclei of the hypothalamus
J. Neuroendocrinol.
Molecular mechanisms of CNS synaptogenesis
Trends Neurosci.
The developing synapse: construction and modulation of synaptic structures and circuits
Science
Wnts and TGF β in synaptogenesis: old friends signalling at new places
Nat. Rev. Neurosci.
Formation and function of synapses with respect to Schwann cells at the end of motor nerve terminal branches on mature amphibian (Bufo marinus) muscle
J. Neurosci.
Schwann cells express active agrin and enhance aggregation of acetylcholine receptors on muscle fibers
J. Neurosci.
Differential effects of neurotrophins and Schwann cell-derived signals on neuronal survival/growth and synaptogenesis
J. Neurosci.
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