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Model for the pharmacological basis of spontaneous synchronous activity in developing retinas

Grzywacz, Norberto M.
Published in Journal of Neuroscience. 1994, vol. 14, no. 12, p. 7426-39
Abstract Spontaneous waves of bursts of action potentials propagate across the ganglion-cell surface of developing retinas. A recent biophysical model postulated that this propagation is mediated by an increase in extracellular K+, following its ejection from ganglion cells during action potentials. Moreover, the model hypothesized that bursts might terminate due to the accumulation of intracellular Ca2+ and the subsequent activation of a Ca(2+)-dependent K+ conductance in the cells' dendrites. Finally, the model proposed that an excitatory synaptic drive causes a neuromodulation of the waves' properties. To test the feasibility of the model, we performed computer simulations of the network of developing ganglion cells under control and pharmacological-manipulation conditions. In particular, we simulated the effects of neostigmine, Cs+ and TEA, low Ca2+ concentrations, and Co2+. A comparison of the simulations with electrophysiological and pharmacological experimental data recently obtained in turtles (Sernagor and Grzywacz, 1993a), and cats and ferrets (Meister et al., 1991; Wong et al., 1993), showed that the model for the most part is consistent with the behavior of developing retinas. Moreover, modifications of the model to allow for GABAergic inputs onto ganglion cells (Sernagor and Grzywacz, 1994) and poor [K+]out buffering (Connors et al., 1982) improved the model's fits. These results lent further support to important roles of extracellular K+ concentration and synaptic drive for the propagation of waves.
Keywords Aging/physiologyAnimalsCesium/pharmacologyCobalt/pharmacologyComputer SimulationElectrophysiologyHumansModels, NeurologicalPotassium Channel BlockersRetina/drug effects/growth & development/physiologyRetinal Ganglion Cells/physiologyTetraethylammoniumTetraethylammonium Compounds/pharmacology
PMID: 7996185
Note Cover picture (Supplemental data): Computer simulations of spontaneous waves of bursty activity propagating through the ganglion cell layer of developing retinas. The simultaneous activation of two spatially separated groups of ganglion cells at the layer's border results in colliding and annihilating waves. The extracellular potassium concentration, shown in the first sequence of frames, rises up to 10 mM, following extrusion of this ion from the bursting cells. This concentration is about four times the resting concentration, visible in green. Such increase in potassium concentration depolarizes neighbor ganglion cells, causing them to fire (and to real ease more potassium) as shown in the second sequence of frames. Time step between frames is 1 sec, and the corresponding physical dimensions of this 241 ganglion cell layer are 364 um for the width and 240 um for the height. See Burgi and Grzywacz, pp. 7426-7439.
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BURGI, Pierre-Yves, GRZYWACZ, Norberto M. Model for the pharmacological basis of spontaneous synchronous activity in developing retinas. In: Journal of Neuroscience, 1994, vol. 14, n° 12, p. 7426-39.

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Deposited on : 2011-11-18

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