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Timm Schubert, Blanca Arango-Gonzalez, Eberhart Zrenner, Thomas Euler, Wadood Haq; Network Oscillations in the Outer Retina in the Rod-Degenerated Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):717.
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© ARVO (1962-2015); The Authors (2016-present)
In the outer retina, neurons form highly conserved synaptic microcircuits. When photoreceptors degenerate, these microcircuits undergo structural alterations leading to remodeling of synaptic connectivity. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. This substantial remodeling of retinal microcircuits may lead to the generation of spontaneous oscillatory activity in the outer retina. Therefore, investigating activity in the remodeled outer rd1 retina is crucial in two ways: First, to understand what general synaptic mechanisms underlie oscillatory activity in the rd1 retina. Second, to identify potential means for suppressing such oscillatory activity. The latter is important, as it may greatly improve applicability of optogenetic approaches and electronic implants as treatments for vision loss.
To assess the neuronal connectivity in the remodeled, light-insensitive rd1 outer retina functionally, we recorded spontaneous population activity in rd1 retinal wholemounts using Ca2+ imaging and identified the participating cell types post-recording using immunolabeling.
Focusing on cones, horizontal cells (HCs) and RBCs, we found all recorded cell types displaying spontaneous oscillatory activity. Many cells formed synchronously active clusters, comprising cones and/or RBCs, but also pure HC clusters were observed. Our pharmacological data suggest that spontaneous synchronous oscillations were initiated by small “islands” of electrically-coupled remnant cones driving RBCs and HCs via ectopic glutamatergic synapses. Cone activity, in turn, was modulated by GABAergic feedback from HCs. Blocking gap junctions decoupled clusters and suppressed most activity except in a few cones, suggesting that electrical coupling plays a crucial role in generating synchronized oscillations in the rd1 outer retina.
In conclusion, degeneration-induced remodeling of the rd1 retina results in a self-sustained outer retinal oscillatory network that complements (and potentially drives) the recently described inner retinal oscillatory network consisting of amacrine cells, bipolar cells and ganglion cells.
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