Gap junctions set the speed and nucleation rate of stage I retinal waves

Abstract

Spontaneous waves in the developing retina are essential in the formation of the retinotopic mapping in the visual system. From experiments in rabbits, it is known that the earliest type of retinal waves (stage I) is nucleated spontaneously, propagates at a speed of 451±91 μ m/sec and relies on gap junction coupling between ganglion cells. Because gap junctions (electrical synapses) have short integration times, it has been argued that they cannot set the low speed of stage I retinal waves. Here, we present a theoretical study of a two-dimensional neural network of the ganglion cell layer with gap junction coupling and intrinsic noise. We demonstrate that this model can explain observed nucleation rates as well as the comparatively slow propagation speed of the waves. From the interaction between two coupled neurons, we estimate the wave speed in the model network. Furthermore, using simulations of small networks of neurons (N≤260), we estimate the nucleation rate in the form of an Arrhenius escape rate. These results allow for informed simulations of a realistically sized network, yielding values of the gap junction coupling and the intrinsic noise level that are in a physiologically plausible range.

On the potential role of lateral connectivity in retinal anticipation

“…This effect is negligible for symmetric gap junctions. Note that symmetric gap junctions are known to favour waves propagation, for example in the early development (stage I, see [ 49 ] and the reference therein for a recent numerical investigation). Here, gap junctions are considered in a different context due to the presence of a nonstationary stimulus triggering the wave.…”

Circuit mechanisms underlying embryonic retinal waves

“…Interestingly, pure gap junction-mediated waves, such as those we observed in the β2-nAChR KO mouse, are considerably slower than waves in WT retina. A recent computational model of gap junction-mediated stage 1 waves, where waves are initiated by RGCs undergoing rare and random depolarizations that propagate entirely via electrical synapses, argues that the speed of propagation is limited by the slow rate at which the junctional currents charge up the membrane capacitance of neighboring RGCs ( Kähne et al, 2019 ). Hence, the faster speed of waves mediated by a combination of nAChRs and gap junctions indicates that diffuse release of ACh leads to faster propagation than electrical synapses alone.…”

On the potential role of lateral connectivity in retinal anticipation

“…This effect is negligible for symmetric gap junctions. Note that symmetric gap junctions are known to favour waves propagation, for example in the early development (stage I, see [42] and reference therein for a recent numerical investigation). Here gap junctions are considered in a different context, due to the presence of a non stationary stimulus, triggering the wave.…”