The nervous system has a modular architecture with neurons of the same type commonly organized in nonrandom arrays or mosaics. Modularity is essential to parallel processing of sensory information and has provided a key element for brain evolution, but we still know very little of the way neuronal mosaics form during development. Here we have identified the immature elements of two retinal mosaics, the choline acetyltransferase (ChAT) amacrine cells, by their early expression of the homeodomain protein Islet-1, and we show that spatial ordering is an intrinsic property of the two Islet-1 mosaics, dynamically maintained while new elements are inserted into the mosaics. Migrating Islet-1 cells do not show this spatial ordering, indicating that they must move tangentially as they enter the mosaic, under the action of local mechanisms. Clonal territory analysis in X-inactivation transgenic mice confirms the lateral displacement of ChAT amacrine cells away from their clonal columns of origin, and mathematical models show how short-range cellular interactions can guide the assemblage of these mosaics via a simple biological rule. Key words: retina; LIM proteins; Islet-1; X-inactivation transgenic mouse; ChAT amacrine; tangential migration; Voronoi domainsThe retina is one of the best examples of modular organization in neural circuitry. The five main types of retinal neurons are organized into three cell layers. Photoreceptors occupy the outer nuclear layer, bipolar, horizontal, and amacrine cells the inner nuclear layer (I N L), and ganglion cells and displaced amacrine cells the ganglion cell layer (GCL). Each principal class of retinal neurons can be divided f urther into subtypes, which differ in morphology and connectivity as well as biochemical and physiological properties (for review, see Ramon y C ajal, 1892;Rodieck, 1973;Dowling, 1987;Wässle and Boycott, 1991). Within each layer, neurons of the same type are commonly spaced in an orderly manner, forming planar arrays that uniformly tile the retina. Such arrays are known as neuronal mosaics (Wässle and Riemann, 1978) because they bring to mind the regular arrangement of the tesserae of a mosaic.Although the orderly organization of retinal cells is known to be f undamental to the parallel processing of visual information in the retina, little is known of the way neuronal mosaics form during development. Postmitotic retinal neurons migrate to their final positions from the proliferative neuroepithelium, but known markers for retinal mosaics are expressed only after the cells have attained a regular spatial arrangement (Wässle and Riemann, 1978;Mitrofanis et al., 1988;Vaney, 1990;C asini and Brecha, 1991;Wikler and Rakic, 1991;Hutsler and Chalupa, 1995;Scheibe et al., 1995), making it difficult to understand how such regularity comes about.Here we report that the transcription factor Islet-1 is an early marker for cholinergic amacrine cells. Islet-1, a member of the LIM homeodomain family known to be involved in vertebrate and invertebrate development (Thor et al...
The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are-strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes.
The distributions of rod and cone photoreceptors have been determined in the retina of the California ground squirrel, Spermophilus beecheyi. Retinas were fixed by perfusion and the rods and cones were detected with indirect immunofluorescence using opsin antibodies. Local densities were determined at 2-mm intervals across the entire retina, from which total numbers of each receptor type were estimated and isodensity distributions were constructed. The ground squirrel retina contains 7.5 million cones and 1.27 million rods. The peak density for the cones (49,550/mm2) is found in a horizontal strip of central retina 2 mm ventral to the elongated optic nerve head, falling gradually to half this value in the dorsal and ventral retinal periphery. Of the cones, there are 14 M cones for every S cone. S cone density is relatively flat across most of the retina, reaching a peak (4500/mm2) at the temporal end of the visual streak. There is one exception to this, however: S cone density climbs dramatically at the extreme dorso-nasal retinal margin (20,000/mm2), where the local ratio of S to M cones equals 1. Rod density is lowest in the visual streak, where the rods comprise less than 5% of the local photoreceptor population, increasing conspicuously in the ventral retina, where the rods achieve 30% of the local photoreceptor population (13,000/mm2). The functional importance of the change in S to M cone ratio at the dorsal circumference of the retina is compromised by the extremely limited portion of the visual field subserved by this retinal region. The significance for vision, if any, remains to be determined. By contrast, the change in rod/cone ratio between the dorsal and ventral halves of the retina indicates a conspicuous asymmetry in the ground squirrel's visual system, suggesting a specialization for maximizing visual sensitivity under dim levels of illumination in the superior visual field.
Elevated intraocular pressure may lead to retinal ganglion cell injury and consequent visual deficits. Chronic intraocular pressure increase is a major risk factor for glaucoma, a leading blinding disease, and permanent visual deficits can also occur following acute pressure increments due to trauma, acute glaucoma or refractive surgery. How pressure affects retinal neurons is not firmly established. Mechanical damage at the optic nerve head, reduced blood supply, inflammation and cytotoxic factors have all been called into play. Reasoning that the analysis of retinal neurons soon after pressure elevation would provide useful cues, we imaged individual ganglion cells in isolated rat retinas before and after short hydrostatic pressure increments. We found that slowly rising pressure to peaks observed in trauma, acute glaucoma or refractive surgery (50-90 mmHg) did not damage ganglion cells, whereas a rapid 1 min pulse to 50 mmHg injured 30% of these cells within 1 h. The severity of damage and the number of affected cells increased with stronger or repeated insults. Degrading extracellular ATP or blocking the P2X receptors for ATP prevented acute pressure-induced damage in ganglion cells. Similar effects were observed in vivo. A short intraocular pressure transient increased extracellular ATP levels in the eye fluids and damaged ganglion cells within 1 h. Reducing extracellular ATP in the eye prevented damage to ganglion cells and accelerated recovery of their response to light. These data show that rapid pressure transients induce acute ganglion cell injury and unveil the causal role of extracellular ATP elevation in such injury.
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