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The Journal of Neuroscience, November 10, 2004, 24(45):10149-10158; doi:10.1523/JNEUROSCI.3203-04.2004

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Development/Plasticity/Repair
Glutamate-Evoked Alterations of Glial and Neuronal Cell Morphology in the Guinea Pig Retina

Ortrud Uckermann,1 Lydia Vargová,2,3 Elke Ulbricht,1 Christoph Klaus,1 Michael Weick,1,3 Katja Rillich,1 Peter Wiedemann,4 Andreas Reichenbach,1 Eva Syková,2,3 and Andreas Bringmann4

1Paul-Flechsig-Institute of Brain Research, University of Leipzig, D-04109 Leipzig, Germany, 2Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic, 3Department of Neuroscience, Charles University Second Medical School, Prague 116 36, Czech Republic, and 4Department of Ophthalmology and Eye Clinic, University of Leipzig, D-04103 Leipzig, Germany

Neuronal activity is accompanied by transmembranous ion fluxes that cause cell volume changes. In whole mounts of the guinea pig retina, application of glutamate resulted in fast swelling of neuronal cell bodies in the ganglion cell layer (GCL) and the inner nuclear layer (INL) (by ~40%) and a concomitant decrease of the thickness of glial cell processes in the inner plexiform layer (IPL) (by ~40%) that was accompanied by an elongation of the glial cells, by a thickening of the whole retinal tissue, and by a shrinkage of the extracellular space (by ~18%). The half-maximal effect of glutamate was observed at ~250 µM, after ~4 min. The swelling was caused predominantly by AMPA-kainate receptor-mediated influx of Na+ into retinal neurons. Similar but transient morphological alterations were induced by high K+ and dopamine, which caused release of endogenous glutamate and subsequent activation of AMPA-kainate receptors. Apparently, retinal glutamatergic transmission is accompanied by neuronal cell swelling that causes compensatory morphological alterations of glial cells. The effect of dopamine was elicitable only during light adaptation but not in the dark, and glutamate and high K+ induced strong ereffects in the dark than in the light. This suggests that not only the endogenous release of dopamine but also the responsiveness of glutamatergic neurons to dopamine is regulated by light-dark adaptation. Similar morphological alterations (neuronal swelling and decreased glial process thickness) were observed in whole mounts isolated immediately after experimental retinal ischemia, suggesting an involvement of AMPA-kainate receptor activation in putative neurotoxic cell swelling in the postischemic retina.

Key words: glutamate; dopamine; ATP; neuroglia; circadian phase; ischemia; retina


Received May 4, 2004; revised September 15, 2004; accepted October 1, 2004.




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