Synaptically-induced sodium transients in glial cells
Final Report Abstract
At glutamatergic synapses, astrocytes mediate the clearance of glutamate from the extracellular space by the high-affinity transporters GLAST and GLT-1. Glutamate uptake is energized by the inward transport of three sodium ions and one proton, while one potassium ion is transported out of the cell. Is has been shown earlier in astrocytes in culture, that activation of glutamate transport causes significant increases in the intracellular sodium concentration. Because such sodium elevations stimulate Na+/K+-ATPase and cause increased glucose uptake, it was suggested that they might serve as key signals in neuro-metabolic coupling. Our goal was to unravel the properties and spatial profiles of sodium transients in glial cells that accompany synaptic transmission in the intact tissue, which were still largely unexplored. Using quantitative sodium imaging our work provided for the first time a detailed description and analysis of activity-induced Na+ transients in Bergmann glial cells and Purkinje neurons of cerebellar tissue slices of the mouse brain. We could show that synaptic activity induces Na+ transients of up to 9 mM in the processes of Bergmann glial cells, which are mainly caused by activation of glutamate uptake. Our findings indicated that sodium transients in Bergmann glial cells, in concert with a membrane depolarization and changes in the concentrations of other ions, result in a long-lasting reduction of the driving force for glutamate uptake. They might thus provide a negative feedback mechanism on glutamate uptake promoting the diffusion of glutamate and the activation of extrasynaptic glutamate receptors. Synaptically-induced sodium transients were also detected in astrocytes of the CA1 "stratum radiatum" of the juvenile mouse hippocampus. Hippocampal astrocytes displayed differences in amplitude and time course of activity-induced sodium signals between different cellular regions. With low stimulation intensities, sodium signals were defined to one-two primary branches and adjacent fine processes, whereas increasing the number of activated synapses resulted in global sodium transients that included the soma. Sodium transients in astrocytes were mainly mediated by activation of glutamate transport. They were however not restricted to the site of sodium influx, but spread along processes of individual astrocytes at an initial velocity of >60 µm/s, a value several times higher than that of classical calcium waves. Sodium signals spread in a radial manner to virtually all neighbouring astrocytes, a process which was primarily based on diffusion through gap junctions composed of Cx30 and Cx43. Our finding that long-lasting sodium signals are present in astrocytes following neuronal release of glutamate supports the proposed tight link between excitatory neuronal activity, glutamate transport, sodium signals and glucose utilization by astrocytes.
Publications
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Properties of the new fluorescent Na+ indicator CoroNa Green: Comparison with SBFI and confocal Na+ Imaging. Journal of Neuroscience Methods, Vol. 155. 2006, Issue 2, pp. 251–259.
Meier SD, Kovalchuk Y, Rose CR
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Imaging glial glutamate uptake in the cerebellum. Proceedings Glial Cells in Health and Disease, London, 4 – 8 September 2007, Neuron Glia Biology, Vol.3. 2007, Suppl. S1–S32.
Bennay, M., Kafitz, K.W., Meier, S.D., Rose, C.R.
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Sodium signals in cerebellar Purkinje neurons and Bergmann glial cells evoked by glutamatergic synaptic transmission. Glia, Vol. 56.2008, Issue 10, pp. 1138–1149.
Bennay, M., Langer, J., Meier, S.D., Kafitz, K.W., Rose, C.R.
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Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nature Neuroscience, Vol. 12. 2009, pp. 1285 - 1292.
Filosa A, Paixão S, Honsek SD, Carmona M, Becker L, Feddersen B, Gaitanos L, Rudhard Y, Schoepfer R, Klopstock T, Kullander K, Rose CR, Pasquale EB, Klein R.
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Synaptically-induced sodium signals in hippocampal astrocytes in situ. The Journal of Physiology, Vol. 587. 2009, Issue 24, pp. 5859–5877.
Langer J., Rose C.R.
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Ion changes and signalling in perisynaptic glia. Brain Research Reviews, Vol. 63. 2010, Issues 1–2, pp. 113–129.
Deitmer, J.W., & Rose C.R.
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Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ. Glia, Vol. 60. 2012, Issue 2, pp. 239–252.
Langer J, Stephan J, Theis M, Rose CR
