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Evelyne Sernagor, Matthias Hennig, Alessandro Maccione, Mauro Gandolfo, Jens-Oliver Muthmann, Stephen Eglen, Luca Berdondini; Following the Ontogeny of Retinal Waves: Pan-Retinal Recordings of Population Dynamics in the Neonatal Mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4563.
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© ARVO (1962-2015); The Authors (2016-present)
The immature retina is characterized by spontaneous waves of spiking activity sweeping across the ganglion cell layer (GCL) during a limited postnatal developmental period. The spatiotemporal patterns encoded in the waves are believed to be instructive for the wiring of functional connections throughout the visual system. This would imply a thorough understanding of how the dynamics of the waves change with development. However, the ontogeny of retinal waves is still poorly understood because most studies have investigated them at low spatiotemporal resolution within restricted retinal areas and over a narrow developmental time range. To address this important issue, we have investigated the ontogeny of mouse retinal waves at near-cellular resolution and at pan-retinal level from birth until eye opening.
We recorded waves from the GCL in retinal wholemounts isolated from wild type (C57Bl6) and cone rod homeobox (Crx) knockout mice (model of Leber congenital amaurosis) using the Active Pixel Sensor multielectrode array, a novel large-scale, high-density system consisting of 4,096 electrodes (21x21 μm size, 42 μm separation, 64x64 configuration) covering an active area of 7.12 mm2 (Berdondini et al., Lab on Chip, 2009), virtually encompassing the entire neonatal mouse retina and recording from ~20% of the entire GCL .
We found that early cholinergic waves propagate with random trajectories over large areas, recruiting few ganglion cells in their path. They become slower and smaller when GABAA signalling matures, beyond postnatal day (P) 7, and at the same time they become denser. Glutamatergic influences dominate from P10, coinciding with profound changes in activity dynamics. Indeed, at that time waves cease to be random, beginning to show repetitive trajectories confined to a few localized hotspots. These hotspots gradually tile the retina with time, and disappear at eye opening.
Our novel observations demonstrate that retinal waves undergo major spatiotemporal changes during ontogeny. These changes could not have been detected with more conventional recording approaches. Our results support the hypothesis that cholinergic waves guide the refinement of retinal targets while glutamatergic waves may support the wiring of retinal receptive fields. In support, patterned spontaneous activity is strongly perturbed from P10 in the Crx-/- mouse.
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