A reaction-diffusion model of cholinergic retinal waves

TL;DR

This paper presents a reaction-diffusion model of cholinergic retinal waves that captures their dynamics and links wave features to physiological parameters, aiding experimental manipulation and understanding of retinal development.

Contribution

It introduces a biophysically consistent reaction-diffusion model that connects retinal wave dynamics to underlying cellular and molecular mechanisms, surpassing previous simulation-based approaches.

Findings

Model accurately reproduces observed wave patterns in mouse retina

ACh concentration modulates wave activity and size

Refractory period influences wave variability

Abstract

Prior to receiving visual stimuli, spontaneous, correlated activity called retinal waves drives activity-dependent developmental programs. Early-stage waves mediated by acetylcholine (ACh) manifest as slow, spreading bursts of action potentials. They are believed to be initiated by the spontaneous firing of Starburst Amacrine Cells (SACs), whose dense, recurrent connectivity then propagates this activity laterally. Their extended inter-wave intervals and shifting wave boundaries are the result of the slow after-hyperpolarization of the SACs creating an evolving mosaic of recruitable and refractory cells, which can and cannot participate in waves, respectively. Recent evidence suggests that cholinergic waves may be modulated by the extracellular concentration of ACh. Here, we construct a simplified, biophysically consistent, reaction-diffusion model of cholinergic retinal waves capable of recapitulating wave dynamics observed in mice retina recordings. The dense, recurrent connectivity of SACs is modeled through local, excitatory coupling occurring via the volume release and diffusion of ACh. In contrast with previous, simulation-based models, we are able to use non-linear wave theory to connect wave features to underlying physiological parameters, making the model useful in determining appropriate pharmacological manipulations to experimentally produce waves of a prescribed spatiotemporal character. The model is used to determine how ACh mediated connectivity may modulate wave activity, and how the noise rate and sAHP refractory period contributes to critical wave size variability.