MODEL FOR THE PHARMACOLOGICAL BASIS OF SPONTANEOUS SYNCHRONOUS ACTIVITY IN DEVELOPING RETINAS

Spontaneous waves of bursts of action potentials propagate across the ganglion-cell surface of developing retinas. A recent biophysical mode l postulated that this propagation is mediated by an increase in extra cellular K+, following its ejection from ganglion cells during action potentials. Moreover, the model hypothesized that bursts might termina te due to the accumulation of intracellular Ca2+ and the subsequent ac tivation of a Ca2+-dependent K+ conductance in the cells' dendrites. F inally, the model proposed that an excitatory synaptic drive causes a neuromodulation of the waves' properties. To test the feasibility of t he model, we performed computer simulations of the network of developi ng ganglion cells under control and pharmacological-manipulation condi tions. In particular, we simulated the effects of neostigmine, Cs+ and TEA, low Ca2+ concentrations, and Co2+. A comparison of the simulatio ns with electrophysiological and pharmacological experimental data rec ently obtained in turtles (Sernagor and Grzywacz, 1993a), and cats and ferrets (Meister et al., 1991; Wong et al., 1993), showed that the mo del for the most part is consistent with the behavior of developing re tinas. Moreover, modifications of the model to allow for GABAergic inp uts onto ganglion cells (Sernagor and Grzywacz, 1994) and poor [K+](ou t) buffering (Conners et al., 1982) improved the model's fits. These r esults lent further support to important roles of extracellular K+ con centration and synaptic drive for the propagation of waves.