Circuit mechanisms underlying embryonic retinal waves

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated stage 1 waves. Using a custom-built macroscope to record spontaneous calcium transients from whole embryonic retinas, we show that stage 1 waves are initiated at several locations across the retina and propagate across a broad range of areas. Blocking gap junctions reduced the frequency and size of stage 1 waves, nearly abolishing them. Global blockade of nAChRs similarly nearly abolished stage 1 waves. Thus, stage 1 waves are mediated by a complex circuitry involving subtypes of nAChRs and gap junctions. Stage 1 waves in mice lacking the beta 2 subunit of the nAChRs (beta 2-nAChR-KO) persisted with altered propagation properties and were abolished by a gap junction blocker. To assay the impact of stage 1 waves on retinal development, we compared the spatial distribution of a subtype of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), which undergo a significant amount of cell death, in WT and beta 2-nAChR-KO mice. We found that the developmental decrease in ipRGC density is preserved between WT and beta 2-nAChR-KO mice, indicating that processes regulating ipRGC numbers and distributions are not influenced by spontaneous activity.

Automated summary

Spontaneous activity plays an important role in the development of neural systems. This study focuses on embryonic retinal waves, specifically stage 1 waves, and reveals their spatiotemporal properties and underlying mechanisms. The results suggest that stage 1 waves are mediated by a circuit involving specific types of receptors and gap junctions. The impact of stage 1 waves on retinal development, particularly on the distribution of a subtype of retinal ganglion cells, is also investigated.