Abstract
During early development, waves of activity propagate across the retina and play a key role in the proper wiring of the early visual system. During a particular phase of the retina development (stage II) these waves are triggered by a transient network of neurons, called Starburst Amacrine Cells (SACs), showing a bursting activity which disappears upon further maturation. The underlying mechanisms of the spontaneous bursting and the transient excitability of immature SACs are not completely clear yet. While several models have attempted to reproduce retinal waves, none of them is able to mimic the rhythmic autonomous bursting of individual SACs and reveal how these cells change their intrinsic properties during development. Here, we introduce a mathematical model, grounded on biophysics, which enables us to reproduce the bursting activity of SACs and to propose a plausible, generic and robust, mechanism that generates it. The core parameters controlling repetitive firing are fast depolarizing V-gated calcium channels and hyperpolarizing V-gated potassium channels. The quiescent phase of bursting is controlled by a slow after hyperpolarization (sAHP), mediated by calcium-dependent potassium channels. Based on a bifurcation analysis we show how biophysical parameters, regulating calcium and potassium activity, control the spontaneously occurring fast oscillatory activity followed by long refractory periods in individual SACs. We make a testable experimental prediction on the role of voltage-dependent potassium channels on the excitability properties of SACs and on the evolution of this excitability along development. We also propose an explanation on how SACs can exhibit a large variability in their bursting periods, as observed experimentally within a SACs network as well as across different species, yet based on a simple, unique, mechanism. As we discuss, these observations at the cellular level have a deep impact on the retinal waves description.
Highlights
Retinal waves, observed in many vertebrate species - chicks[1], ferrets[2], mice[3], turtles[4], macaques[5] etc. are spontaneous bursts of activity propagating in the developing retina and playing a fundamental role in shaping the visual system and retinal circuitry
Starburst Amacrine Cells (SACs), which are cells forming a lattice right above the ganglion cells layer, are found to exhibit spontaneous intrinsic rhythmic bursting activity, which disappears upon maturation[6]
We derive a biophysical set of equations, describing the bursting activity of immature SACs, following experimental observations regarding the ionic currents involved in their bursting[6]
Summary
Retinal waves, observed in many vertebrate species - chicks[1], ferrets[2], mice[3], turtles[4], macaques[5] etc. are spontaneous bursts of activity propagating in the developing retina and playing a fundamental role in shaping the visual system and retinal circuitry. During early development, these cells have a different role; they are responsible for eliciting stage II retinal waves via their spontaneous bursting behavior induced by autonomous intrinsic cellular mechanisms[6]. This activity disappears completely upon maturation[6]. Cells return back to the quiescent state allowing a long after hyperpolarization phase This bifurcation analysis reveals a mechanism for SACs rhythmic bursting, interpretable with respect to biophysics and the experiments of Zheng et al.[6,14] on individual immature SACs dynamics. We include a short review on the comparison of existing models
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