title: Model for the pharmacological basis of spontaneous synchronous activity in developing retinas.
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.
authors.affiliation: Smith-Kettlewell Eye Research Institute, San Francisco, California 94115.
authors.forename: P Y
authors.initials: PY
authors.lastname: Burgi
authors.forename: N M
authors.initials: NM
authors.lastname: Grzywacz
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002586:Cesium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003198:Computer Simulation; D004594:Electrophysiology; D006801:Humans; D008959:Models, Neurological; D026902:Potassium Channel Blockers; D012160:Retina / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D002586:Cesium; D003035:Cobalt; D019789:Tetraethylammonium