New roles for astrocytes: Regulation of CNS synaptogenesis

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.

[1]  R. Nicoll,et al.  Distinct Roles for Ionotropic and Metabotropic Glutamate Receptors in the Maturation of Excitatory Synapses , 2000, The Journal of Neuroscience.

[2]  I. Kaiserman,et al.  Ion channels in presynaptic nerve terminals and control of transmitter release. , 1999, Physiological reviews.

[3]  C. Göritz,et al.  Role of glia-derived cholesterol in synaptogenesis: new revelations in the synapse–glia affair , 2002, Journal of Physiology-Paris.

[4]  B. Barres,et al.  Control of synapse number by glia. , 2001, Science.

[5]  M. Werle,et al.  Matrix metalloproteinase-3 removes agrin from synaptic basal lamina. , 2000, Journal of neurobiology.

[6]  S. Okabe,et al.  Visualizing synapse formation and remodeling: recent advances in real-time imaging of CNS synapses , 2001, Neuroscience Research.

[7]  L. Garcia-Segura,et al.  Role of astroglia in estrogen regulation of synaptic plasticity and brain repair. , 1999, Journal of neurobiology.

[8]  F. Seil,et al.  Interactions between cerebellar Purkinje cells and their associated astrocytes. , 2001, Histology and histopathology.

[9]  A. Araque,et al.  Dynamic signaling between astrocytes and neurons. , 2001, Annual review of physiology.

[10]  Noam E Ziv,et al.  Assembly of New Individual Excitatory Synapses Time Course and Temporal Order of Synaptic Molecule Recruitment , 2000, Neuron.

[11]  R. Balice-Gordon,et al.  Activity-dependent editing of neuromuscular synaptic connections , 2000, Brain Research Bulletin.

[12]  C. Stiles,et al.  Molecular mechanisms controlling cortical gliogenesis , 2002, Current Opinion in Neurobiology.

[13]  Jean-Antoine Girault,et al.  Development of nodes of Ranvier , 2002, Current Opinion in Neurobiology.

[14]  K. Murai,et al.  Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling , 2003, Nature Neuroscience.

[15]  S. Oliet.  Functional Consequences of Morphological Neuroglial Changes in the Magnocellular Nuclei of the Hypothalamus , 2002, Journal of neuroendocrinology.

[16]  V. Budnik,et al.  Wnts and TGFβ in synaptogenesis: old friends signalling at new places , 2003, Nature Reviews Neuroscience.

[17]  R. Riquelme,et al.  Bergmann Glia GABAA Receptors Concentrate on the Glial Processes That Wrap Inhibitory Synapses , 2002, The Journal of Neuroscience.

[18]  F. Pfrieger.  Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[19]  D. Mitter,et al.  The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content , 2002, Journal of neurochemistry.

[20]  C. Göritz,et al.  CNS synaptogenesis promoted by glia-derived cholesterol. , 2001, Science.

[21]  P. Marin,et al.  Proteomic Analysis of Astrocytic Secretion in the Mouse , 2003, Journal of Biological Chemistry.

[22]  F. Gomes,et al.  Cross-talk between neurons and glia: highlights on soluble factors. , 2001, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[23]  J. Mong,et al.  Steroid-induced developmental plasticity in hypothalamic astrocytes: implications for synaptic patterning. , 1999, Journal of neurobiology.

[24]  G. Cao,et al.  Schwann Cells Express Active Agrin and Enhance Aggregation of Acetylcholine Receptors on Muscle Fibers , 2001, The Journal of Neuroscience.

[25]  Yishi Jin,et al.  Synaptogenesis: insights from worm and fly , 2002, Current Opinion in Neurobiology.

[26]  J. Barker,et al.  Astrocytes regulate the developmental appearance of GABAergic and glutamatergic postsynaptic currents in cultured embryonic rat spinal neurons , 1999, European Journal of Neuroscience.

[27]  戸田 弘紀.  Neurons generated from adult rat hippocampal stem cells form functional glutamatergic and GABAergic synapses in vitro , 2001 .

[28]  R. Fields,et al.  New insights into neuron-glia communication. , 2002, Science.

[29]  G. I. Hatton.  Function-related plasticity in hypothalamus. , 1997, Annual review of neuroscience.

[30]  Yangzhou Du,et al.  Oligodendrocytes as providers of growth factors , 2002, Journal of neuroscience research.

[31]  R. Robitaille,et al.  Glial cells as active partners in synaptic functions. , 2001, Progress in brain research.

[32]  S. Cohen-Cory.  The Developing Synapse: Construction and Modulation of Synaptic Structures and Circuits , 2002, Science.

[33]  D. Colman,et al.  Organizing Principles of the Axoglial Apparatus , 2001, Neuron.

[34]  N. Danbolt.  Glutamate uptake , 2001, Progress in Neurobiology.

[35]  A. Bacci,et al.  Astrocytes are required for the oscillatory activity in cultured hippocampal neurons , 1999, The European journal of neuroscience.

[36]  H. Atwood,et al.  Diversification of synaptic strength: presynaptic elements , 2002, Nature Reviews Neuroscience.

[37]  A. Villa,et al.  Agrin Controls Synaptic Differentiation in Hippocampal Neurons , 2000, The Journal of Neuroscience.

[38]  Heike Hering,et al.  Lipid Rafts in the Maintenance of Synapses, Dendritic Spines, and Surface AMPA Receptor Stability , 2003, The Journal of Neuroscience.

[39]  Shiaoping C. Zhu,et al.  A Glia-Derived Signal Regulating Neuronal Differentiation , 2000, The Journal of Neuroscience.

[40]  J. Milbrandt,et al.  Lipid rafts in neuronal signaling and function , 2002, Trends in Neurosciences.

[41]  J. Trachtenberg,et al.  Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions , 1996, Trends in Neurosciences.

[42]  F. Pfrieger,et al.  Synaptic efficacy enhanced by glial cells in vitro. , 1997, Science.

[43]  M. Bennett,et al.  Formation and Function of Synapses with Respect to Schwann Cells at the End of Motor Nerve Terminal Branches on Mature Amphibian (Bufo marinus) Muscle , 2001, The Journal of Neuroscience.

[44]  F. Pfrieger.  Role of cholesterol in synapse formation and function. , 2003, Biochimica et biophysica acta.

[45]  J. Trimmer,et al.  Developmental clustering of ion channels at and near the node of Ranvier. , 2001, Developmental biology.

[46]  P. Scheiffele.  Cell-cell signaling during synapse formation in the CNS. , 2003, Annual review of neuroscience.

[47]  F. Pfrieger,et al.  Glia‐derived signals induce synapse formation in neurones of the rat central nervous system , 2001, The Journal of physiology.

[48]  Wade Morishita,et al.  Control of Synaptic Strength by Glial TNFα , 2002, Science.

[49]  W. Kakegawa,et al.  Glia-Synapse Interaction Through Ca2+-Permeable AMPA Receptors in Bergmann Glia , 2001, Science.

[50]  H. Peng,et al.  Differential Effects of Neurotrophins and Schwann Cell-Derived Signals on Neuronal Survival/Growth and Synaptogenesis , 2003, The Journal of Neuroscience.

[51]  T. Sims,et al.  Schwann cell-induced loss of synapses in the central nervous system , 2000, Brain Research.

[52]  Mary Mazzanti,et al.  Astrocytes selectively enhance N‐type calcium current in hippocampal neurons , 2003, Glia.

[53]  Pierre J. Magistretti,et al.  The tripartite synapse: glia in synaptic transmission , 2002 .

[54]  N. Ziv,et al.  Molecular mechanisms of CNS synaptogenesis , 2002, Trends in Neurosciences.

[55]  Frank W Pfrieger,et al.  New views on synapse—glia interactions , 1996, Current Opinion in Neurobiology.

[56]  D. Poulain,et al.  Maternity leads to morphological synaptic plasticity in the oxytocin system. , 2001, Progress in brain research.

[57]  C. Lesuisse,et al.  Regulation of agrin expression in hippocampal neurons by cell contact and electrical activity. , 2000, Brain research. Molecular brain research.

[58]  B. Gusterson,et al.  Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain , 2001, Glia.

[59]  M. Poo,et al.  Retrograde signaling in the development and modification of synapses. , 1998, Physiological reviews.

[60]  K. Belmonte,et al.  Developmental Expression of Muscarinic Acetylcholine Receptors in Chick Retina: Selective Induction of M2 Muscarinic Receptor Expression In Ovo by a Factor Secreted by Müller Glial Cells , 2000, The Journal of Neuroscience.

[61]  A. Araque,et al.  Tripartite synapses: glia, the unacknowledged partner , 1999, Trends in Neurosciences.

[62]  R. Robitaille,et al.  Perisynaptic Schwann Cells at the Neuromuscular Junction: Nerve- and Activity-Dependent Contributions to Synaptic Efficacy, Plasticity, and Reinnervation , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[63]  Virginia M. Y. Lee,et al.  Functional synapses are formed between human NTera2 (NT2N, hNT) neurons grown on astrocytes , 1999, The Journal of comparative neurology.

[64]  F. Gage,et al.  Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons , 2002, Nature Neuroscience.

[65]  K. Svoboda,et al.  Activity-Dependent Synaptogenesis in the Adult Mammalian Cortex , 2002, Neuron.

[66]  Junhyong Kim,et al.  Unwrapping Glial Biology Gcm Target Genes Regulating Glial Development, Diversification, and Function , 2003, Neuron.

[67]  D. Spencer,et al.  Differential neurite growth on astrocyte substrates: interspecies facilitation in green fluorescent protein-transfected rat and human neurons , 1999, Neuroscience.

[68]  J. Sanes,et al.  Development of the vertebrate neuromuscular junction. , 1999, Annual review of neuroscience.