Cells In Peripheral Retina Research Articles

Amacrine and bipolar inputs to midget and parasol ganglion cells in marmoset retina

Retinal ganglion cells receive excitatory synapses from bipolar cells and inhibitory synapses from amacrine cells. Previous studies in primate suggest that the strength of inhibitory amacrine input is greater to cells in peripheral retina than to foveal (central) cells. A comprehensive study of a large number of ganglion cells at different eccentricities, however, is still lacking. Here, we compared the amacrine and bipolar input to midget and parasol ganglion cells in central and peripheral retina of marmosets (Callithrix jacchus). Ganglion cells were labeled by retrograde filling from the lateral geniculate nucleus or by intracellular injection. Presumed amacrine input was identified with antibodies against gephyrin; presumed bipolar input was identified with antibodies against the GluR4 subunit of the AMPA receptor. In vertical sections, about 40% of gephyrin immunoreactive (IR) puncta were colocalized with GABAA receptor subunits, whereas immunoreactivity for gephyrin and GluR4 was found at distinct sets of puncta. The density of gephyrin IR puncta associated with ganglion cell dendrites was comparable for midget and parasol cells at all eccentricities studied (up to 2 mm or about 16 degrees of visual angle for midget cells and up to 10 mm or >80 degrees of visual angle for parasol cells). In central retina, the densities of gephyrin IR and GluR4 IR puncta associated with the dendrites of midget and parasol cells are comparable, but the average density of GluR4 IR puncta decreased slightly in peripheral parasol cells. These anatomical results indicate that the ratio of amacrine to bipolar input does not account for the distinct functional properties of parasol and midget cells or for functional differences between cells of the same type in central and peripheral retina.

Transmission of colour and acuity signals by parvocellular cells in marmoset monkeys

The red-green axis of colour vision evolved recently in primate evolutionary history. Signals serving red-green colour vision travel together with signals serving spatial vision, in the parvocellular (PC) division of the subcortical visual pathway. However, the question of whether receptive fields of PC pathway cells are specialized to transmit red-green colour signals remains unresolved. We addressed this question in single-cell recordings from the lateral geniculate nucleus of anaesthetized marmosets. Marmosets show a high proportion of dichromatic (red-green colour-blind) individuals, allowing spatial and colour tuning properties of PC cells to be directly compared in dichromatic and trichromatic visual systems. We measured spatial frequency tuning for sine gratings that provided selective stimulation of individual photoreceptor types. We found that in trichromatic marmosets, the foveal visual field representation is dominated by red-green colour-selective PC cells. Colour selectivity of PC cells is reduced at greater eccentricities, but cone inputs to centre and surround are biased to create more selectivity than predicted by a purely 'random wiring' model. Thus, one-to-one connections in the fovea are sufficient, but not necessary, to create colour-selective responses. The distribution of spatial tuning properties for achromatic stimuli shows almost complete overlap between PC cells recorded in dichromatic and trichromatic marmosets. These data indicate that transmission of red-green colour signals has been enabled by centre-surround receptive fields of PC cells, and has not altered the capacity of PC cells to serve high-acuity vision at high stimulus contrast.

Modulation sensitivity of ganglion cells in peripheral retina of macaque

There is ample psychophysical evidence that flicker is more salient in the peripheral than the central visual field, but the physiological basis of this eccentricity-dependant change is unclear. Here, we compared responsivity to temporal modulation of ganglion cells in central and peripheral primate retina. Above 30 Hz modulation frequency, both magnocellular (MC) and parvocellular (PC) pathway cells are more responsive in peripheral retina. This suggests that an increase in high-frequency temporal responsiveness arises in outer retina before the MC and PC pathways diverge. In both central and peripheral retina, the critical fusion frequency of MC cells is higher than that of PC cells. This result is consistent with other evidence that psychophysical flicker sensitivity is mediated by the MC pathway.

Chromatic sensitivity of ganglion cells in the peripheral primate retina.

Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field.

The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation.

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 microm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

Number of neurons in the retinal ganglion cell layer of the quokka wallaby do not change throughout life.

During adult life, the topography of the retinal pigment epithelium (RPE) of the quokka wallaby changes gradually. Cells in peripheral retina enlarge in surface area while those in mid-temporal retina, adjacent to the area centralis, a high density region in the ganglion cell layer, decrease in area, implying that the tissue in this area is drawing together. We speculated that high ganglion cell densities in temporal regions might be maintained, in the face of cell loss due to aging, by this apparent drawing together of the RPE sheet. Therefore, we examined the retinal ganglion cell layer of the quokka in cresyl violet stained wholemounts from animals aged from 0. 55 to 13.5 years. We found that total neuron number in the retinal ganglion cell layer of the quokka did not decrease significantly throughout life even though individuals in captivity live long lives (9-15 years). Ganglion and amacrine cells were counted separately and identified by strict morphological criteria. Nevertheless, the proportion of ganglion to amacrine cells appeared to decrease linearly throughout life, indicating that the morphology of a proportion of neurons became more amacrine-like during aging. Mean cell size did not change throughout life. In the quokka, retinal area increases slowly throughout life and may account for the small reduction in cell density seen in most retinal regions.

Costratification of a population of bipolar cells with the direction-selective circuitry of the rabbit retina

We have stained a new population of bipolar cells in rabbit retina by using antibodies against the carbohydrate epitope, CD15. The CD15-positive bipolar cells comprise 6-8% of the total cone bipolar cells in peripheral retina. Their axonal and dendritic arbors are similar in size and range from 15 to 50 pm in diameter. The axonal arbors are narrowly stratified in sublamina b of the inner plexiform layer. Double label experiments using an antibody against the calcium binding protein, calbindin, or an antibody against protein kinase C, demonstrate that the CD15-positive bipolar cells are a separate population from the previously identified calbindin-positive cone bipolar cells and the rod bipolar cells. Labeling the processes of starburst amacrine cells with antibodies against choline acetyltransferase showed that the CD15-positive bipolar cells stratify within and slightly more distally to the processes of the ON-starburst amacrine cells. Confocal images of retinal wholemounts showed that the axons of the CD15-positive bipolar cells follow the pattern of the ON-starburst cells' processes. Axonal varicosities of the CD15-positive bipolar cells penetrate the bundles formed by the processes of the ON-starburst cells. This finding suggests that the CD15-positive bipolar cell provides input to the ON-starburst amacrine cells and/or the ON-plexus of the ON-OFF direction-selective ganglion cells.

Immunocytochemical characterization and spatial distribution of midget bipolar cells in the macaque monkey retina

Midget bipolar cells form the first distinct step in the parvocellular ( P)-pathway of the primate visual system, and are the major determinant of the receptive field properties of colour selective midget ganglion cells. This paper describes the sampling properties of the midget bipolar cell population and relates this to the processing of chromatic information in the P-pathway. Immunocytochemical markers were used to label midget bipolar cells so that their spatial density could be compared with that of cones and ganglion cells. Sections through macaque monkey retinae were immunostained with antibodies against cholecystokinin (CCK), and recoverin. In CCK-labelled sections, in addition to blue cone bipolar cells, numerous thin bipolar cell dendrites, which could be associated with individual cone pedicles are stained. CCK-immunoreactive midget bipolar cells are found throughout the retina. A different population of midget bipolar cells is revealed in recoverin-labelled sections. Based on a comparison with midget bipolar cells in Golgi-stained retinae we propose that ON-midget (invaginating) bipolars are imntunoreactive for CCK and confirm that OFF-midget (flat) bipolar cells are immunoreactive for recoverin [Milam, Dacey and Dizhoor (1993) Visual Neuroscience, 10, 1–12). The density of recoverin labelled midget bipolars matches the cone density to an eccentricity of about 10 mm; from there outwards it drops to 60% of the cone density. This suggests convergence of several cones to individual midget bipolar cells in peripheral retina. We conclude that midget bipolar cells are present throughout the entire primate retina, and could, in peripheral as well as in central retina, provide chromatically specific input to the P-pathway.

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.