Direct signaling from astrocytes to neurons in cultures of mammalian brain cells.

Although astrocytes have been considered to be supportive, rather than transmissive, in the adult nervous system, recent studies have challenged this assumption by demonstrating that astrocytes possess functional neurotransmitter receptors. Astrocytes are now shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons. When a focal electric field potential was applied to single astrocytes in mixed cultures of rat forebrain astrocytes and neurons, a prompt elevation of calcium occurred in the target cell. This in turn triggered a wave of calcium increase, which propagated from astrocyte to astrocyte. Neurons resting on these astrocytes responded with large increases in their concentration of cytosolic calcium. The gap junction blocker octanol attenuated the neuronal response, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically. This neuronal response to local astrocytic stimulation may mediate local intercellular communication within the brain.

[1]  K. Willecke,et al.  Differential expression of three gap junction proteins in developing and mature brain tissues. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Hertzberg,et al.  Gap junction protein in rat hippocampus: Correlative light and electron microscope immunohistochemical localization , 1989, The Journal of comparative neurology.

[3]  W G Wier,et al.  Rapid communication between neurons and astrocytes in primary cortical cultures , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  S. B. Kater,et al.  Local increases in intracellular calcium elicit local filopodial responses in helisoma neuronal growth cages , 1992, Neuron.

[5]  S Kriegler,et al.  Calcium signaling of glial cells along mammalian axons , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  C. Giaume,et al.  Effects of General Anesthetics on Intercellular Communications Mediated by Gap Junctions between Astrocytes in Primary Culture , 1993, Anesthesiology.

[7]  M. Sanderson,et al.  Intercellular calcium signaling via gap junctions in glioma cells , 1992, The Journal of cell biology.

[8]  S. Robinson,et al.  Unidirectional coupling of gap junctions between neuroglia. , 1993, Science.

[9]  A. Charles,et al.  Intercellular signaling in glial cells: Calcium waves and oscillations in response to mechanical stimulation and glutamate , 1991, Neuron.

[10]  A. Hansen,et al.  Effect of anoxia on ion distribution in the brain. , 1985, Physiological reviews.

[11]  A. Jensen,et al.  Fluorescence measurement of changes in intracellular calcium induced by excitatory amino acids in cultured cortical astrocytes , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  J. Trosko,et al.  A fluorescence photobleaching assay of gap junction-mediated communication between human cells. , 1986, Science.

[13]  Stephen J. Smith,et al.  Neuronal activity triggers calcium waves in hippocampal astrocyte networks , 1992, Neuron.

[14]  R. Yuste,et al.  Extensive dye coupling between rat neocortical neurons during the period of circuit formation , 1993, Neuron.

[15]  T. Murphy,et al.  Spontaneous synchronous synaptic calcium transients in cultured cortical neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  W. Pulsinelli,et al.  Acid-induced death in neurons and glia , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  S. Finkbeiner,et al.  Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. , 1990, Science.

[18]  W. Loewenstein,et al.  Asymmetrically permeable membrane channels in cell junction. , 1980, Science.

[19]  D. Spray,et al.  Gap junctions in the brain: where, what type, how many and why? , 1993, Trends in Neurosciences.

[20]  S. Finkbeiner Calcium waves in astrocytes-filling in the gaps , 1992, Neuron.

[21]  S. J. Smith,et al.  Neurally evoked calcium transients in terminal Schwann cells at the neuromuscular junction. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Nicholson,et al.  Tetrodotoxin resistant propagation and extracellular sodium changes during spreading depression in rat cerebellum , 1982, Brain Research.