This review deals with a phenomenon which, although it has been known for five decades, has not been recognized until recently as a suitable tool for investigations of neuronal-glial interactions an the interesting consequences of the non-linearities arising from these cooperative effects, such as the transition from quiescent states to the propagation of excitation. For neurophysiologists interested in the excitability control of neuronal populations, the retinal spreading depression wave can also be very useful, especially as a basic model for epileptic activity triggering and propagation mechanisms. In the isolated eye cup, spreading depression waves (RSDs) can be observed with ease. In fact, the RSD wave can be seen with the naked eye, which gives the observer a complete and non-invasive two-dimensional view of propagation. In the intrinsic optical signal of the RSD, several components can be separated, either by their spectral preferences or by their temporal and spatial characteristics and experimental manipulations. Glial membrane channel activity and physical changes in the composition of the extracellular medium appear to the major contributions for the optical changes during RSDs. Different components are also found in the electrophysiological concomitants of the waves, some with neuronal (synaptic terminals) and some with glial predominance. Besides the clinical and physiological aspects, the RSDs are part of a general class of self-organizing spatiotemporal structures that arise in systems far from equilibrium known as dissipative structures. In the retina, low dimensional dissipative structures self-organized, self-sustained and spatially structured wave activity, can be maintained for hours either as a soliton 'circling wave' or as a complex sequence of interacting spirals. Therefore, the RSD can serve as a powerful tool for cross-disciplinary research in the field of non-linear dynamics.164657690Adey, W.R., Molecular aspects of cell membranes as substrates for interaction with electromagnetic fields (1983) Synergetics of the Brain, pp. 201-213. , E. Basar, H. Flohr, H. Haken and A. J. Mandell, eds. Springer, BerlinAdey, W.R., Cell membranes, electromagnetic fields and intercellular communication (1989) Brain Dynamics, pp. 26-42. , E. Basar and T. H. Bullock, eds. Springer, BerlinAmit, D.J., (1988) Modelling Brain Function, , The World of Attractor Neural Networks. Cambridge University Press, CambridgeBallany, K.P., Graphe, P., Bruggencate, G., Ion activities and potassium uptake mechanism of glial cells in guinea pig olphactory cortex slices (1987) J. Physiol., 382, pp. 159-174Bawin, S.M., Kazmarek, L.K., Adey, W.R., Effects of modulated VHF fields on the central nervous system (1975) Ann. N. Y. Acad. Sci., 247, pp. 74-91Bawin, S.M., Adey, W.R., Sensitivity of calcium binding in cerebral tissue to weak environmental electric fields oscillatint at low frequencies (1976) Proc. Natn. Acad. Sci. U.S.A., 73, pp. 1999-2003Brandt, S., Hanke, W., Temporal delay of onset of retinal spreading depression waves after mechanical stimulation of the tissue (1996) J. Brain Res., 37 (2), pp. 202-203Bures, J., Block of Leão's spreading depression by bivalent cations (1960) Physiol. Bohemoslov., 9, pp. 202-209Bures, J., Buresova, O., Krivanek, J., (1974) The Mechanism and Applications of Leão's Spreading Depression of Electroencephalogram, , Academic Press, New YorkBures, J., Buresova, O., Krivaneck, J., Brain and behaviour paradigms for research (1988) Neural Mechanisms, , Academia, PrahaBures, J., Buresova, O., Krivaneck, J., Susceptibility to spreading depression and anoxia, regional differences and drug control (1988) Mechanisms of Cerebral Ischemia and Stroke, pp. 253-267. , G. Somjem, ed., Plenum Press, New YorkBures, J., History of spreading depression (1993) Migraine: Basic Mechanisms and Treatment, pp. 279-292. , A. Lehmenküller, K. H. Grotemeyer and F. Tegtmeier, eds. Urban-Schwarzenberg, MunichCastellucci, V.F., Goldring, S., Contribution to steady potential shift of slow depolarisation in cells presumed to be glia (1970) EEG Clin. Neurophysiol., 28, pp. 109-118Chance, B., Cohen, F.F., Jöbsis, B., Schoener, B., Intracellular oxidation-reduction states in vivo (1962) Science, 137, pp. 499-508Chesler, M., Kraig, R.P., Intracellular pH transients of mammalian astrocytes (1987) J. Neurosci., 9, pp. 159-174Cohen, L.B., Keynes, R.D., Changes in light scattering associated with the action potential in crab nerves (1971) J. Physiol. (Lond.), 212, pp. 259-275Coveney, P., Highfield, R., (1990) The Arrow of Time, , Fawcett Columbine, New YorkDavidenko, J.M., Pertsov, A.V., Salomonz, R., Baxter, W., Jalife, J., Stationary and drifting spiral waves of excitation in isolated cardiac muscle (1992) Nature, 355, pp. 349-351DoCarmo, R.J., (1992) Spreading Depression, , Springer, BerlinDoCarmo, R., Martins-Ferreira, H., Spreading depression of Leão probed with ion-sensitive microelectrodes in isolated chicken retina (1984) Ann. Acad. Bras. Cienc., 56, pp. 401-421Dowling, J., (1987) The Retina: An Approachable Part of the Brain, , Harvard University Press, Cambridge, USADutta, S.K., Subramanian, A., Ghosh, B., Parshad, R., Microwave radiation-induced calcium efflux from brain tissue (1984) Bioelectromagnetism, 5, pp. 71-78Fernandes De Lima, V.M., Goldermann, M., Hanke, W., Calcium waves in grey matter are due to voltage-sensitive glial membrane channels (1994) Brain Res., 663, pp. 77-83Fernandes De Lima, V.M., Hanke, W., Observations of non-stationarities in extracellular potassium within the grey matter neuropil during self-sustained SDs (1996) J. Brain Res., , in pressFernandes De Lima, Goldermann, M., Hanke, W., The Retinal Spreading Depression: A Tool for Interdisciplinary Research, , Cambridge Academic Press (in press)Fernandes De Lima, V.M., Hanke, W., Long range interactions in the triggering and onset of retinal spreading depression waves (1996) J. Brain Res., 37 (2), pp. 200-201Fernandes De Lima, V.M., Hanke, W., Schlue, W.R., The SD in the chicken retina as a model of self-organized, sustained and structured activity within the CNS (1993) Migraine Basic Mechanisms and Treatment, pp. 563-572. , A. Lemehnkhüler, K. H. Grotemeyer and F. Tegtmeyer, eds. Urban-Schwarzenberg, MunichFernandes De Lima, V.M., Scheller, D., Hanke, W., Tegtmeyer, F., Schlue, W.R., Neuronal-glia interactions during 'en masse' propagating activity. The retinal SD as a good pharmacological tool (1993) Migraine Basic Mechanisms and Treatment, pp. 547-562. , A. Lehmenküler, K. H. Grotemeyer and F. Tegtmeyer, eds. Urban-Schwarzenberg, MunichFernandes De Lima, V.M., Scheller, D., Tegmeyer, F., Hanke, W., Schlue, W.R., Self-sustained spreading depression in the chicken retina and short term neuronal-glial interactions within the gray matter neuropil (1993) Brain Res., 614, pp. 45-51Fernandes De Lima, V.M., Pijn, J.P., Nunes Felipe, C.M., Lopes Da Silva, F.H., The role of the hippocampal commissures in the interhemispheric transfer of epileptiform after discharges in the rat: A study using linear and non-linear regression analysis (1990) EEG Clin. Neurophysiol., 76, pp. 520-539Gainer, H., Wolfe, S., Obaid, A.L., Salzberg, B.M., Action potentials and frequency dependent secretion in the mouse neurohypophysis (1986) Neuroendocrinology, 43, pp. 557-563Goldermann, M., Hanke, W., Long distance interactions in excitation-depression events of the central nervous system (1996) J. Brain Res., 37 (2), p. 210Gorelova, N., Bures, J., Spiral waves of spreading depression in isolated chicken retina (1983) J. Neurobiol., 19, pp. 154-171Gouras, P., Spreading depression of activity in amphibian retina (1958) Am. J. Physiol., 195, pp. 28-32Grossman, R.G., Glial-neural interaction studied with intracellular injections of ions into glial cells (1978) Dynamic Properties of Glial Cells, , E. Schoffeniels, G. Franck, L. Hertz and D. B. Tower, eds. Pergamon Press, OxfordGrossman, R.G., Hampton, T.L., Depolarisation of cortical glial cells during electrocortical activity (1968) Brain Res., 11, pp. 316-324Guedes, R.A., DoCarmo, R., Influence of ionic disturbances produced by gastric washing on cortical spreading depression (1980) Exp. Brain Res., 39, pp. 341-349Hanawa, I., Kuge, K., Matsumura, K., Studies on the slow depressive potential of the isolated frog retina (1967) Japan. J. Physiol., 17, pp. 321-334Hanke, W., Fernandes De Lima, V.M., Schlue, W.R., Single ion-channels behaviour measured in the intact chicken retina during spreading depression (1993) Migraine Basic Mechanisms and Treatment, pp. 573-582. , A. Lehmenkhüler, K. H. Grotemeyer and F. Tegtmeyer, eds. Urban-Schwarzenberg, MunichHill, D.K., Keynes, R.D., Opacity changes in stimulated nerve (1949) J. Physiol. (Lond.), 108, pp. 278-281Hoch, M., Jackle, H., Pattern formation in the early Drosophilla embryo (1992) Spatio-Temporal Organization in Nonequilibrium Systems, pp. 96-99. , S. Müller and Plesser, eds. Projekt, DortmundKarahashi, Y., Goldring, S., Intracellular potentials from 'idle' cells in cerebral cortex of cat (1966) EEG Clin. Neurophysiol., 20, pp. 600-607Kinzell, W., Spin glasses as models systems for neural networks (1986) Complex-Systems, Operational Approaches, pp. 107-114. , H. Haken, ed. Springer, BerlinKow, L.-M., Van Harreveld, A.V., Ion and water movement in isolated chicken retinas during spreading depression (1972) J. Neurobiol., 2, pp. 61-69Krivanek, J., Some metabolic changes accompanying Leão's spreading cortical depression in the rat (1961) J. Neurochem., 6, pp. 183-189Lauritzen, M., Cortical spreading depression as a putative migraine mechanism (1987) Trends Neurosci., 10, pp. 8-13Lauritzen, M., Cortical spreading depression as a migraine mechanism: Clinical and experimental aspects (1992) Spreading Depression, pp. 7-16. , R. J. DoCarmo, ed., Springer, BerlinLeão, A.A.P., Spreading depression of activity in cerebral the cortex (1944) J. Neurophysiol., 7, pp. 359-390Leão, A.A.P., Pial circulation and spreading depression of activity in the cerebral cortex (1944) J. Neurophysiol., 10, pp. 391-396Leão, A.A.P., Further observation on the spreading depression of activity in the cerebral cortex J. Neurophysiol., 10, pp. 409-419Leão, A.A.P., Martins-Ferreira, H., Alteração da impedancia elétrica no decurso da depressão alastrante da atividade do cortex cerebral (1953) Ann. Acad. Bras. Cienc., 25, pp. 259-266Leão, A.A.P., Morrison, R.S., (1945) Propagation of Spreading Cortical DepressionLechleiter, J.D., Clapham, D., Intracellular calcium waves: Propagation, annihilation and excitability Spatio-Temporal Organization in Nonequilibrium Systems, pp. 135-137. , S. Müller and T. Plesser, eds. Projekt, DortmundLev-Ram, V., Grinvald, A., AC and K-dependent communication between central nervous system oligodendrocytes revealed by voltage-sensitive dyes (1986) Proc. Natn. Acad. Sci. U.S.A., 83, pp. 6651-6656Lin-Liu, S., Adey, W.R., Low frequency, amplitude-modulated microwave fields change calcium efflux rates from synaptosomes (1982) Bioelectromagnetics, 3, pp. 309-322MacVicar, B.A., Hochmann, D., Imaging of synaptically evoked intrinsic optical signals in hippocampal slice (1991) J. Neurosci., 11 (5), pp. 1458-1489Marshall, W.H., Spreading cortical depression of Leão (1959) Physiol. Rev., 39, pp. 239-279Martins-Ferreira, H., Spreading depression in the chicken retina (1983) The Brain and Behaviour of the Fowl, pp. 317-333. , T. Ookawa, ed., Japan Scientific Society Press, TokyoMartins-Ferreira, H., Propagation of spreading depression in isolated chicken retina (1993) Migraine: Basic Mechanisms and Treatment, pp. 533-546. , A. Lehmenküller, K. H. Grotemeyer and F. Tegtmeier, eds. Urban-Schwarzenberg, MunichMartins-Ferreira, H., Oliveira E Castro, G., Spreading depression in isolated chick retina (1971) Vision Res. Suppl., 3, pp. 171-184Martins-Ferreira, H., Oliveira E Castro, G., Light scattering changes accompanying spreading depression in the isolated chicken retina (1966) J. Neurophysiol., 29, pp. 715-726Martins-Ferreira, H., Oliveira Castro, G., Struchiner, C.J., Rodrigues, P.S., Circling spreading depression in isolated chicken retina (1975) J. Neurophysiol., 37, pp. 773-783Mayevsky, A., Chance, B., Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat (1974) Brain Res., 65, pp. 529-533Mayevsky, A., Zarchin, N., Sonn, J., Brain redox state and O2 balance in experimental spreading depression ischemia (1993) Migraine: Basic Mechanisms and Treatment, pp. 379-394. , A. Lehmenkühller, K. H. Grotemeyer and F. Tegtmeier, eds. Urban-Schwarzenberg, MunichMilner, P.M., Note on a possible correspondence between the scotomas of migraine and spreading depression of Leão (1958) EEG Clin. Neurophysiol., 10, p. 705Mori, S., Miller, W.H., Tomita, T., Müller cell function during spreading depression (SD) in frog retina (1976) Proc. Natn. Acad. Sci. U.S.A., 73, pp. 1351-1354Mori, S., Miller, W.H., Tomita, T., Microelectrode study of spreading depression (SD) in frog retina -general observations of filed potential associated with SD (1976) Japan. J. Physiol., 26, pp. 203-217Mori, S., Miller, W.H., Tomita, T., Microelectrode study of spreading depression in frog retina - Müller cell activity and [K]o during SD (1976) Japan. J. Physiol., 73, pp. 219-233Müller, S.C., Spatial patterns in (Bio)-chemical reactions (1988) From Chemical to Biological Organization, pp. 83-98. , M. Markus, S. C. Müller and G. Nicholis, eds. Springer BerlinNewmann, E.A., Electrophysiology of retinal glial cells (1989) Prog. Ret. Res., 8, pp. 153-171Oliveira E Castro, G., Martins-Ferreira, H., Dual nature of the peaks of light scattering during spreading depression in chick retina (1985) Ann. Acad. Bras. Cien., 57, pp. 95-103Prigogine, I., Stengers, I., (1984) Order Out of Chaos, , Heinemann, LondonRosenthal, M., Somjem, G.G., Spreading depression of cerebral cortex of cats (1973) J. Neurophysiol., 36, pp. 739-749Ross, J., Müller, S.C., Vidal, C., Chemical waves (1988) Science, 240, pp. 460-465Salzberg, B.M., Obaid, A.L., Gainer, H., Large and rapid optical changes in light scattering accompanying secretion in nerve terminals in the mammalian neurohypophysis (1985) J. Gen. Physiol., 86, pp. 395-413Scott, S.K., Chemical reactions as non-linear systems (1992) Non-Linear Sci. Today, 2, pp. 2-13Snow, R.W., Taylor, C.P., Dudek, F.E., Electrophysiological and optical changes in slices of rat hippocampus during spreading depression (1983) J. Neurophysiol., 50, pp. 561-572Somjem, G.G., Aitken, P.G., The ionic and metabolic responses associated with neuronal depression of Leão's type in cerebral cortex and hippocampal formation (1984) Ann. Acad. Bras. Cienc., 56 (4), pp. 495-504Stepnoski, R.A., LaPorta, A., Raccuia-Behling, F., Blonder, G.E., Slusher, R.E., Kleinfeld, D., Noninvasive detection of changes in membrane potential in cultured neurons by light scattering (1991) Proc. Natn. Acad. Sci. U.S.A., 88, pp. 9382-9386Streit, D.S., Ferreira, C.R., Martins-Ferreira, H., Spreading depression in isolated spinal cord (1995) J. Neurophysiol., 74, pp. 888-890Sugaya, E., Takato, M., Noda, Y., Neuronal and glial activity during spreading depression in cerebral cortex of cat (1975) J. Neurophysiol., 38, pp. 822-841Tasaki, I., Chang, J.J., Electric response of glial cells in cat brain (1958) Science, 128, pp. 1209-1220Tomita, T., Spreading depression potential in the frog retina (1984) Ann. Acad. Bras. Cienc., 56 (4), pp. 505-517Van Harreveld, A., Two mechanisms for spreading depression in the chicken retina (1978) J. Neurophysiol., 9 (6), pp. 419-431Van Harreveld, A., Visual concomitants of retinal spreading depression (1984) Ann. Acad. Bras. Cienc., 56 (4), pp. 520-523Wiedemann, M., Fernandes De Lima, V.M., Hanke, W., Effects of antimigraine drugs on the retinal spreading depression Naunyn-Schmiedeberg's Arch. Pharmac., , in pressYaary, Y., Konnerth, A., Heinemann, U., Non-synaptic epileptogenesys in the mammalian hippocampus in vitro. II Role of extracellular potassium (1986) J. Neurophysiol., 56 (2), pp. 424-438Zaitkin, A.N., Zhabotinsky, A.M., Concentration wave propagation in two dimensional liquid phase self-oscillation (1970) Nature, 225, pp. 35-537