Spatiotemporal Features of Retinal Waves Instruct the Wiring of the Visual Circuitry

Abstract

Coordinated spontaneous activity is present in different sensory systems during early stages of development. This activity is thought to play a critical role in the development of sensory representations before the maturation of sensory experience. In the visual system, the mechanisms by which spatiotemporal properties of retinal spontaneous activity, called retinal waves, drive developmental events has been well studied. Recent advancements in pharmacological, genetic, and optogenetic manipulations have provided further understanding of the contribution of specific spatiotemporal properties of retinal waves to eye-specific segregation and retinotopic refinement of retinofugal projections. Here we review some of the recent progress in understanding the role of retinal waves in the early stages of visual system development, prior to the maturation of vision.

Keywords: activity-dependent development; eye-specific segregation; ferret; mouse; retinal waves; retinotopy.

Figure 1

Spontaneous retinal waves mediate eye-specific segregation and retinotopic refinement of retinofugal projections. The axons of retinal ganglion cells (RGCs) target the dorsal lateral geniculate nucleus (dLGN) of the thalamus and the superior colliculus (SC). RGC projections from opposite eyes are segregated into ipsilateral and contralateral regions (black/gray oppositions). RGC projections from each retina are retinotopically organized (colored regions). Note that for simplicity we have depicted retinotopic maps only for one eye. Retinotopic maps and eye-specific segregations form for both eyes.

Figure 2

Distinct spatiotemporal patterns of retinal waves instruct different features of retinofugal projections in mice. (A–D) Top: schematic of retinal wave firing patterns. Dots are representative of RGCs with larger dots indicating elevated firing rates during a single retinal wave. Bottom: schematic of retinogeniculate wiring using same code as Figure 1—colored hexagons represent retinotopy while gray/black regions represent eye-specific segregation. (A) Under normal conditions, RGCs exhibit high local correlations while activity of the two retinas is minimally correlated. This pattern of activity supports both eye-specific segregation and retinotopic maps in both the dLGN and SC. (B) High correlations between retinal waves of opposite retinas induced by optogenetic stimulation is detrimental to eye-specific segregation while retinotopic maps are unaffected (Zhang et al., 2011). (C) Disruption of local correlations either by an increase in uncorrelated firing or by abnormally elevated correlations between distant RGCs (global correlations), such as that observed in β2KO and Retβ2-cKO mice, is detrimental to retinotopic map formation. Local correlations are sufficient for normal retinotopic maps in Retβ2-cKO, Rxβ2-cKO and β2(TG) (Xu et al., , ; Burbridge et al., 2014). (D) High global correlations paired with high inter-retina correlations such as that observed in the β2KO mouse, is detrimental to both eye-specific segregation and retinotopic maps (Xu et al., ; Burbridge et al., 2014).