Heinz Wässle

The morphological types of ganglion cells of the domestic cat's retina.

1. Three distinct morphological types of cat retinal ganglion cells have been identified and categorized as α, β and γ. Alpha ganglion cells have dendritic field diameters from 180 to 1000 μm; β, about 25 to 300 μm; γ, 180 to 800 μm, possibly more.

Immunocytochemical analysis of the mouse retina

Transgenic mice provide a new approach for studying the structure and function of the mammalian retina. In the past, the cellular organization of the mammalian retina was investigated preferentially in primates, cats, and rats but rarely in mice. In the current study, the authors applied 42 different immunocytochemical markers to sections of the mouse retina and studied their cellular and synaptic localization by using confocal microscopy. The markers applied were from three major groups: 1) antibodies against calcium‐binding proteins, such as calbindin, parvalbumin, recoverin, or caldendrin; 2) antibodies that recognize specific transmitter systems, such as glycine, γ‐aminobutyric acid, or acetylcholine; and 3) antibodies that recognize transmitter receptors and show their aggregation at specific synapses. Only a few markers labeled only one cell type: Most antibodies recognized specific groups of neurons. These were analyzed in more detail in double‐labeling experiments with different combinations of the antibodies. In light of their results, the authors offer a list of immunocytochemical markers that can be used to detect possible changes in the retinal organization of mutant mice. J. Comp. Neurol. 424:1–23, 2000.

The Mosaic of Nerve Cells in the Mammalian Retina

Cells from three different layers of the retina were tested for regular horizontal arrangement or random distribution. Monkey cones, cat cones, cat A-type horizontal cells and cat alpha-ganglion cells are all arranged in a regular mosaic. This was assessed by measuring the distance to the nearest neighbour of each cell. The nearest neighbour distributions differed significantly from those of random dot patterns. The precision of the mosaic decreased in the order monkey cones, cat cones, cat A-type horizontal cells, cat alpha-ganglion cells. All four cell types were - independent of density - more regularly arranged in the centre of the retina than in the periphery. The advantages of a regular arrangement compared with a random distribution and mechanisms which could generate a regular mosaic are discussed.

GlyR α3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization

Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR α3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR α3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR α3 not only lack the inhibition of glycinergic neurotransmission by PGE2 seen in wild-type mice but also show a reduction in pain sensitization induced by spinal PGE2 injection or peripheral inflammation. Thus, GlyR α3 may provide a previously unrecognized molecular target in pain therapy.

Types of bipolar cells in the mouse retina.

We studied the morphology of bipolar cells in fixed vertical tissue sections (slices) of the mouse retina by injecting the cells with Lucifer Yellow and Neurobiotin. Nine different cone bipolar cell types and one rod bipolar cell type were distinguished. The major criteria for classifying the cells were the branching pattern and stratification level of their axon terminals in the inner plexiform layer (IPL). To assess this, the IPL was subdivided into five strata of equal width. The slices were immunostained for calretinin, which labels three horizontal bands serving as a standard measure for the precise localization of the axon terminals. Immunostaining the retina with antibodies against the G‐protein Gγ13, a marker for ON‐bipolar cells, made it possible to separate OFF‐ and ON‐bipolar cells. At least two OFF‐cone bipolar cells (Types 1 and 2) were immunolabeled with antibodies against the neurokinin 3 receptors (NK3R). A further OFF‐ and an ON‐cone bipolar cell (Types 3 and 5) were immunostained with antibodies against the calcium‐binding protein CaB5. The bipolar cell types described here were compared with previous schemes of rat and primate bipolar cells. Homologous types between the three species are discussed. J. Comp. Neurol. 469:70–82, 2004.

Morphology and mosaic of on- and off-beta cells in the cat retina and some functional considerations

The beta type of ganglion cell can be subdivided in Golgi-stained whole mounts of the cat retina according to the branching level of the dendritic tree in the inner plexiform layer. The dendritic branching level of on-beta cells is nearer to the cell body; that of off-beta cells is about 10 μm further outwards. After horseradish peroxidase (HRP) injection into the lateral geniculate nucleus all beta cells were labelled. In this way it is shown that about 55% of all ganglion cells, irrespective of retinal topography, are beta cells. The spatial distribution of on- and off-beta cells was studied from the HRP-labelled material. On-beta cells form a lattice with regular inter-cell spacings ; off-beta cells are also regularly arrayed. The two lattices are superimposed independently of each other. Beta cells are commonly assumed to be associated with the resolution of fine detail in the cat visual system. The mosaic of beta cells imposes some constraints and permits some predictions to be made with respect to the cat’s visual discrimination.

Morphological Classification of Bipolar Cells of the Primate Retina

Bipolar cells were studied in Golgi‐Colonnier‐stained whole mounts of macaque monkey retinae. A piece of retina, at 6–7 mm eccentricity, was particularly well stained for the analysis of the different bipolar cell types. Many midget bipolar cells were encountered and the dichotomy into flat and invaginating midget bipolars was confirmed. Six types of diffuse cone bipolar cell are distinguished. They differ in their dendritic branching pattern, in the number of cones contacted–usually between five and ten–and in the shape and branching level of their axons. The size, shape and stratification of the axons were found to be the most reliable distinguishing features for classifying diffuse cone bipolar cells. The stratification of the axons in the inner plexiform layer (IPL), whether closer to the amacrine or ganglion cells, was used to name diffuse cone bipolar cells in the order DB1 to DB6. Blue cone and rod bipolar cells were confirmed as distinct types. Axon terminals of diffuse cone bipolars were found to tile their sublamina of the IPL in a territorial manner. From this the density of each type could be estimated, and it is shown that a single cone is likely to be in contact with as many as 15 individual diffuse bipolar cells, as well as two midget bipolars. The diffuse bipolar cells observed contact all the cone pedicles in their dendritic fields. It is, therefore, unlikely that they carry a chromatic signal into the inner retina. The presence of many midget bipolar cells, which make contact with one cone pedicle only, suggests that midget bipolars provide chromatic input to ganglion cells in peripheral retina as well as in the fovea. The data show that the P‐ and M‐cell pathways of the primate visual system are, to a significant extent, already anatomically discrete at the photoreceptor synapse.

Morphology and Topography of on- and off-Alpha Cells in the Cat Retina

Neurofibrillar staining methods were found to stain all alpha cells of the cat retina completely, that is the perikaryon, the axon and the dendritic branches. The dendrites of the alpha cells in vertical sections were found to be unistratified and to occupy two narrow strata in the outer half of the inner plexiform layer. This difference in branching level could also be observed in whole-mount preparations and it has been demonstrated in the preceding paper (Peichl & Wässle 1981) that it corresponds to the physiological on‒off dichotomy. Thus the topographical distribution of on- and off-alpha cells could be studied. They were found to occur in about equal numbers. Both on- and off-alpha cell perikarya form a regular lattice and both lattices are superimposed independently. The dendritic branches of neighbouring alpha cells overlap and each retinal point is covered by the dendritic field of at least one on- and one off-alpha cell. The dendritic trees of on-alpha cells seem to have more small branches and are on the average smaller than those of off-alpha cells. The density of alpha cells was found to peak in the central area whence it continuously decreased towards the retinal periphery.

Retinal ganglion cell density and cortical magnification factor in the primate.

The question of whether the large area occupied by the primate fovea in the visual cortex (V1) is the result of a selective amplification of the central visual field, or whether it merely reflects the ganglion cell density of the retina, has been a subject of debate for many years. Measurements of the ganglion cell densities are made difficult by lateral displacements of cells around the fovea and the occurrence of amacrine cells in the ganglion cell layer. We have now identified and counted these amacrine cells by GABA immunocytochemistry and by retrograde degeneration of ganglion cells. By reconstructing the fovea from vertical and horizontal serial sections, we were able to measure the densities of cones, cone pedicles and ganglion cells within the same retina. We found 3-4 ganglion cells for every foveal cone. This ratio decreased to one ganglion cell per cone at an eccentricity of 15-20 deg (3-4 mm) and in peripheral retina there are more cones than ganglion cells. The ganglion cell density changes by a factor of 1000-4000 between peripheral and central retina. A comparable gradient has been reported for the representation of the peripheral and central visual field in V1. We suggest that ganglion cell density can fully account for the cortical magnification factor and there is no need to postulate a selective amplification of the foveal representation.

Cone Contacts, Mosaics, and Territories of Bipolar Cells in the Mouse Retina

We report a quantitative analysis of the different bipolar cell types of the mouse retina. They were identified in wild-type mice by specific antibodies or in transgenic mouse lines by specific expression of green fluorescent protein or Clomeleon. The bipolar cell densities, their cone contacts, their dendritic coverage, and their axonal tiling were measured in retinal whole mounts. The results show that each and all cones are contacted by at least one member of any given type of bipolar cell (not considering genuine blue cones). Consequently, each cone feeds its light signals into a minimum of 10 different bipolar cells. Parallel processing of an image projected onto the retina, therefore, starts at the first synapse of the retina, the cone pedicle. The quantitative analysis suggests that our proposed catalog of 11 cone bipolar cells and one rod bipolar cell is complete, and all major bipolar cell types of the mouse retina appear to have been discovered.