Spatial-Temporal Patterns of Retinal Waves Underlying Activity-Dependent Refinement of Retinofugal Projections

Abstract

During development, retinal axons project coarsely within their central visual targets before refining to form precisely organized synaptic connections. Spontaneous retinal activity, in the form of acetylcholine-driven retinal waves, is widely proposed to be necessary for establishing these precise projection patterns. In particular, both axonal terminations of retinal ganglion cells (RGCs) and the size of receptive fields of neurons in visual areas of the brain are larger in mice that lack the β2 subunit of the nicotinic acetylcholine receptor (β2KO). Here, using a large-scale, high-density multi-electrode array to record single-unit activity from hundreds of RGCs simultaneously, we present analysis of early post-natal retinal activity from both wild type (WT) and β2KO retinas. We find that β2KO retinas have correlated patterns of activity, but many aspects of these patterns differ from those of WT retina. Quantitative analysis of these differences suggests that wave directionality, coupled with short-distance correlated bursting patterns of RGCs, work together to drive refinement of retinofugal projections.

Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits

“…In particular, waves in β2KO mice were less frequent and many RGCs fired action potentials that were not associated with retinal waves and therefore were not significantly correlated with one another, in agreement with previous studies (8,9,21,24) (Fig. 1B).…”

“…In addition, rod and cone photoreceptors are not yet photosensitive and do not contribute to ganglion cell light responses (19). WT recordings confirmed previous observations (7,9,20,21), where RGCs fired periodic bursts of action potentials that swept across the retina as a wave (Fig. 1A).…”

“…The developing retina also shows robustness against perturbations in circuits that generate spontaneous retinal waves (4). For example, disruption of normal cholinergic transmission during the first postnatal week leads to the generation of waves via a distinct gap junction coupled network (7)(8)(9). These observations indicate that degenerate circuit mechanisms exist in the developing retina to maintain spontaneous activity.…”

Receptive field center size decreases and firing properties mature in ON and OFF retinal ganglion cells after eye opening in the mouse

“…Oscillatory release of neurotransmitter from bipolar cells may be an intrinsic property of retinal circuitry (Petit-Jacques et al 2005). Spontaneous retinal activity occurs in the early postnatal retina through the first week after eye opening (Blankenship et al 2009;Meister et al 1991;Stafford et al 2009;Wong 1999). While these retinal "waves" are well characterized, many neurons in the retina have been shown to exhibit spontaneous and light-driven oscillatory activity over a large range of frequencies and ages (Neuenschwander et al 1999;Petit-Jacques and Bloomfield 2008;Petit-Jacques et al 2005).…”

A Sparse Multiwavelet-Based Generalized Laguerre–Volterra Model for Identifying Time-Varying Neural Dynamics from Spiking Activities

“…A set of spontaneous retinal spike train recordings has been used to illustrate and reveal the potential properties of the neural dynamics [46]. The dataset contains 512 electrodes recordings from retina of rats.…”