The role of early neural activity in the maturation of turtle retinal function

Abstract

In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials long before the eye becomes exposed to sensory experience at birth. These early bursts are synchronised between neighbouring retinal ganglion cells (RGCs), yielding unique spatiotemporal patterns: ‘waves’ of activity sweep across large retinal areas every few minutes. Both at retinal and extraretinal levels, these embryonic retinal waves are believed to guide the wiring of the visual system using hebbian mechanisms of synaptic strengthening.

In the first part of this review, we recapitulate the evidence for a role of these embryonic spontaneous bursts of activity in shaping developing complex receptive field properties of RGCs in the turtle embryonic retina. We also discuss the role of visual experience in establishing RGC visual functions, and how spontaneous activity and visual experience interact to bring developing receptive fields to maturation. We have hypothesised that the physiological changes associated with development reflect modifications in the dendritic arbours of RGCs, the anatomical substrate of their receptive fields. We demonstrate that there is a temporal correlation between the period of receptive field expansion and that of dendritic growth. Moreover, the immature spontaneous activity contributes to dendritic growth in developing RGCs. Intracellular staining of RGCs reveals, however, that immature receptive fields only rarely show direct correlation with the layout of the corresponding dendritic tree. To investigate the possibility that not only the presence of the spontaneous activity, but even the precise spatiotemporal patterns encoded in retinal waves might contribute to the refinement of retinal neural circuitry, first we must clarify the mechanisms mediating the generation and propagation of these waves across development. In the second part of this review, we present evidence that turtle retinal waves, visualised using calcium imaging, exhibit profound changes in their spatiotemporal patterns during development. From fast waves sweeping across large retinal areas and recruiting many cells on their trajectory at early stages, waves become slower and eventually stop propagating towards hatching, when they become stationary patches of neighbouring coactive RGCs. A developmental switch from excitatory to inhibitory GABA_A responses appears to mediate the modification in spontaneous activity patterns while the retina develops. Future chronic studies using specific spatiotemporal alterations of the waves will shed a new light on how the wave dynamics help in sculpting retinal receptive fields.