  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.
