PubMed Health⌕ Search

Biomedical subjects

D M Dacey

Publications and source records attributed to D M Dacey.

At least 19 recordsLinked to original sources

Characterization and use of a digital light projector for vision research.

For creating stimuli in the laboratory, digital light projection (DLP) technology has the potential to overcome the low output luminance, lack of pixel independence, and limited chromaticity gamut of the cathode ray tube (CRT). We built a DLP-based stimulator for projecting patterns on the in vitro primate retina. The DLP produces high light levels and has good contrast. Spatial performance was similar to that of a CRT. Temporal performance was limited by the refresh rate (63 Hz). The chromatic gamut was modestly larger than that of a CRT although the primary spectra varied to a small degree with light output and numerical aperture.

Analog-Digital Conversion↗

Primate horizontal cell dynamics: an analysis of sensitivity regulation in the outer retina.

The human cone visual system maintains sensitivity over a broad range of illumination, from below 1 troland to 1,000,000 trolands. While the cone photoreceptors themselves are an important locus for sensitivity regulation-or light adaptation-the degree to which they contribute in primates remains unclear. To determine the range of sensitivity regulation in the outer retina, the temporal dynamics, neural gain control, and response range compression were measured in second-order neurons, the H1 horizontal cells, of the macaque retina. Situated at the first synapse in the retina, H1 cells receive input from a large population of cones. Lee et al. have previously shown that sensitivity regulation in H1 cells is both cone type-specific and spatially restricted. The sensitivity regulation seen in H1 cells at moderate illuminances thus takes place before the summation of cone signals in these cells, and the data establish the H1 cell as a convenient locus for analyzing cone signals. In the present study, cone-driven responses of primate H1 cells to temporally modulated sine-wave stimuli and to increment pulses were measured at steady levels of 1-1,000 trolands. The H1 cell gave a modulated response to sine-wave stimuli and hyperpolarized to increment pulses with overshoots at stimulus onset and offset. The temporal amplitude sensitivity function was primarily low-pass in shape, with a small degree of low-frequency roll off and a resonance shoulder near 40 Hz. A model incorporating a cascade of first-order filters together with an underdamped second-order filter could describe both temporal sinusoidal and pulse hyperpolarizations. Amplitude sensitivity was estimated from both pulse and sine-wave data as a function of the steady adaptation level. Sensitivity at low light levels (1 troland) showed a slowing in temporal dynamics, indicating time-dependent sensitivity regulation. Sensitivity was reduced at light levels above approximately 10 trolands, reflecting both response range compression and neural gain control. Thus the outer retina is a major locus for sensitivity regulation in primates.

Animals↗

Parallel pathways for spectral coding in primate retina.

The primate retina is an exciting focus in neuroscience, where recent data from molecular genetics, adaptive optics, anatomy, and physiology, together with measures of human visual performance, are converging to provide new insights into the retinal origins of color vision. Trichromatic color vision begins when the image is sampled by short- (S), middle- (M) and long- (L) wavelength-sensitive cone photoreceptors. Diverse retinal cell types combine the cone signals to create separate luminance, red-green, and blue-yellow pathways. Each pathway is associated with distinctive retinal architectures. Thus a blue-yellow pathway originates in a bistratified ganglion cell type and associated interneurons that combine excitation from S cones and inhibition from L and M cones. By contrast, a red-green pathway, in which signals from L and M cones are opposed, is associated with the specialized anatomy of the primate fovea, in which the "midget" ganglion cells receive dominant excitatory input from a single L or M cone.

Animals↗

Interindividual and topographical variation of L:M cone ratios in monkey retinas.

We analyzed the ratio of L:M cone photopigment mRNA in the retinas of Old World monkeys, using the method of rapid polymerase chain reaction-single-strand conformation polymorphism. The L:M cone pigment mRNA ratio in whole retina ranged from 0.6 to 7.0, with a mean of approximately 1.6 (standard deviation, +/- 0.56; n = 26). There was no change in this ratio with eccentricity up to 9 mm (approximately 45 degrees), though the ratio was approximately 30% greater in temporal than in nasal retina. The mRNA ratios are in good agreement with the L:M cone ratio in these same retinas, inferred from electrophysiological recordings of cone signal gain in horizontal cell interneurons. The correlation between mRNA ratios and physiological cone gain ratio supports the conclusion that both measures reflect the relative number of L and M cones.

Animals↗

Physiology of L- and M-cone inputs to H1 horizontal cells in the primate retina.

In the primate retina, H1 horizontal cells form an electrically coupled network and receive convergent input from long- (L-) and middle- (M-) wavelength-sensitive cones. Using an in vitro preparation of the intact retina to record the light-evoked voltage responses of H1 cells, we systematically varied the L- and M-cone stimulus contrast and measured the relative L- and M-cone input strength for 137 cells across 33 retinas from three Old World species (Macaca nemestrina, M. fascicularis, and Papio anubis). We found that the L- and the M-cone inputs were summed by the H1 cell in proportion to the stimulus cone contrast, which yielded a measure of what we term L- and M-cone contrast gain. The proportion of L-cone contrast gain was highly variable, ranging from 25% to 90% [mean +/- standard deviation, (60 +/- 14)%]. This variability was accounted for by retinal location within an individual, with the temporal retina showing a consistently higher percentage of L-cone gain, and by large overall variation across individuals, with the mean percentage of L-cone gain ranging from 32% to 80%. We hypothesize that the relative L- and M-cone contrast gain is determined simply by the relative number of L and M cones in the H1 cell's receptive field and that the variability in L- and M-cone contrast gain reflects a corresponding variability in the mosaic of L and M cones.

Animals↗

Horizontal cells reveal cone type-specific adaptation in primate retina.

The human cone visual system maintains contrast sensitivity over a wide range of ambient illumination, a property known as light adaptation. The first stage in light adaptation is believed to take place at the first neural step in vision, within the long, middle, and short wavelength sensitive cone photoreceptors. To determine the properties of adaptation in primate outer retina, we measured cone signals in second-order interneurons, the horizontal cells, of the macaque monkey. Horizontal cells provide a unique site for studying early adaptational mechanisms; they are but one synapse away from the photoreceptors, and each horizontal cell receives excitatory inputs from many cones. Light adaptation occurred over the entire range of light levels evaluated, a luminance range of 15-1,850 trolands. Adaptation was demonstrated to be independent in each cone type and to be spatially restricted. Thus, in primates, a major source of sensitivity regulation occurs before summation of cone signals in the horizontal cell.

Adaptation, Physiological↗

Sensitivity and dynamics of rod signals in H1 horizontal cells of the macaque monkey retina.

We measured the sensitivity, temporal frequency response, latency, and receptive field diameter of rod input to the H1 horizontal cell type in an in vitro preparation of the macaque retina. The H1 cell has both a cone-connected dendritic tree and a long axon-like process that terminates in a rod-connected arbor. We recorded from the H1 cell body where rod signals were distinguished by sensitivity to short wavelength light after dark adaptation. Receptive fields of rod vs. cone mediated responses were coextensive, indicating that the rod signal is transmitted via rod-cone gap junctions. Sensitivity of the H1 cell rod signal was approximately 1 log unit higher than that of the cone signal. Below cone threshold rod signals were temporally low-pass, with a cutoff frequency below 10 Hz. Rod signals became faster and more transient with increasing light levels. We conclude that the H1 cell rod signal is not sensitive in the low scotopic range and, by comparison with the rod signal recorded directly in cones (Schneeweis & Schnapf (1995) Science, 268, 1053-1056), signal transmission across the cone-H1 synapse does not significantly filter the temporal properties of the rod signal.

Adaptation, Ocular↗

Primate retina: cell types, circuits and color opponency.

The link between morphology and physiology for some of the cell types of the macaque monkey retina is reviewed with emphasis on understanding the neural mechanism for spectral opponency in the light response of ganglion cells. An in vitro preparation of the retina is used in which morphologically identified cell types are selectively targeted for intracellular recording and staining under microscopic control. The goal is to trace the physiological signals from the long (L), middle (M) and short-wavelength sensitive (S) cones to identified cell types that participate in opponent and non-opponent signal pathways. Heterochromatic modulation photometry and silent substitution are used to characterize L-, M- or S-cone inputs to the receptive fields of distinct horizontal cell, bipolar cell, ganglion cell and amacrine cell types. The majority of the retinal cell types await detailed analysis, and knowledge of the mechanisms of opponency remains incomplete. However results thus far have established: (1) Horizontal cell interneurons make preferential connections with the three cone types, but cannot provide a basis for spectral opponency in the circuitry of the outer retina. (2) A morphologically distinctive bistratified ganglion cell type transmits a blue-ON yellow-OFF spectral opponent signal to the parvocellular division of lateral geniculate nucleus. The morphology of this ganglion cell type suggests a simple synaptic mechanism for blue yellow opponency via converging input from an S-cone connecting ON-bipolar cell and an L - M cone connecting OFF-bipolar cell. (3) Midget ganglion cells, whose axons project to the parvocellular layers of the lateral geniculate nucleus and are assumed to be the origin of red/green opponent signals, show a non-opponent, achromatic physiology when recorded in the retinal periphery the underlying circuitry for red green opponency thus remains controversial, and (4) recent recordings from identified bipolar and amacrine cells in macaque suggest that a more complete accounting of opponent circuitry is a realistic goal.

Animals↗

Horizontal cells of the primate retina: cone specificity without spectral opponency.

The chromatic dimensions of human color vision have a neural basis in the retina. Ganglion cells, the output neurons of the retina, exhibit spectral opponency; they are excited by some wavelengths and inhibited by others. The hypothesis that the opponent circuitry emerges from selective connections between horizontal cell interneurons and cone photoreceptors sensitive to long, middle, and short wavelengths (L-, M-, and S-cones) was tested by physiologically and anatomically characterizing cone connections of horizontal cell mosaics in macaque monkeys. H1 horizontal cells received input only from L- and M-cones, whereas H2 horizontal cells received a strong input from S-cones and a weaker input from L- and M-cones. All cone inputs were the same sign, and both horizontal cell types lacked opponency. Despite cone type selectivity, the horizontal cell cannot be the locus of an opponent transformation in primates, including humans.

Animals↗

Circuitry for color coding in the primate retina.

Human color vision starts with the signals from three cone photoreceptor types, maximally sensitive to long (L-cone), middle (M-cone), and short (S-cone) wavelengths. Within the retina these signals combine in an antagonistic way to form red-green and blue-yellow spectral opponent pathways. In the classical model this antagonism is thought to arise from the convergence of cone type-specific excitatory and inhibitory inputs to retinal ganglion cells. The circuitry for spectral opponency is now being investigated using an in vitro preparation of the macaque monkey retina. Intracellular recording and staining has shown that blue-ON/yellow-OFF opponent responses arise from a distinctive bistratified ganglion cell type. Surprisingly, this cone opponency appears to arise by dual excitatory cone bipolar cell inputs: an ON bipolar cell that contacts only S-cones and an OFF bipolar cell that contacts L- and M-cones. Red-green spectral opponency has long been linked to the midget ganglion cells, but an underlying mechanism remains unclear. For example, receptive field mapping argues for segregation of L-and M-cone signals to the midget cell center and surround, but horizontal cell interneurons, believed to generate the inhibitory surround, lack opponency and cannot contribute selective L- or M-cone input to the midget cell surround. The solution to this color puzzle no doubt lies in the great diversity of cell types in the primate retina that still await discovery and analysis.

Animals↗

The 'blue-on' opponent pathway in primate retina originates from a distinct bistratified ganglion cell type.

Colour vision in humans and Old World monkeys begins with the differential activation of three types of cone photoreceptor which are maximally sensitive to short (S), medium (M) and long (L) wavelengths. Signals from the three cone types are relayed to the retinal ganglion cells via cone-specific bipolar cell types. Colour-coding ganglion cells fall into two major physiological classes: the red-green opponent cells, which receive antagonistic input from M- and L-sensitive cones, and the blue-yellow opponent cells, which receive input from S-sensitive cones, opposed by combined M- and L-cone input. The neural mechanisms producing colour opponency are not understood. It has been assumed that both kinds of opponent signals are transmitted to the lateral geniculate nucleus by one type of ganglion cell, the midget cell. We now report that a distinct non-midget ganglion cell type, the small bistratified cell, corresponds to the physiological type that receives excitatory input from S cones, the 'blue-on' cell. Our results thus demonstrate an anatomically distinct pathway that conveys S-cone signals to the brain. The morphology of the blue-on cell also suggests a novel hypothesis for the retinal circuitry underlying the blue-yellow opponent response.

Animals↗

Physiology, morphology and spatial densities of identified ganglion cell types in primate retina.

The use of in vitro preparations of primate retina provides new perspectives on the mosaic organization and physiological properties of three ganglion cell types that project to the lateral geniculate nucleus: the parasol, midget and small bistratified cells. Dendritic field sizes and coverage for the three types suggest that their relative densities vary with eccentricity. Of the total ganglion cells in the human fovea, midget cells constitute about 90%, parasol cells about 5%, and small bistratified cells about 1%. In the periphery, midget cells make up about 40-45%, parasol cells about 20% and small bistratified cells about 10% of the total. Thus from peripheral to central retina the number of midget ganglion cells progressively increases relative to the parasol and small bistratified types. Physiological properties of these cells have recently been studied in macaque (Macaca nemestrina) retina by combining intracellular recording and dye injection. As expected, parasol cells, projecting to geniculate magnocellular layers, give phasic, non-opponent light responses. Midget cells, which project to geniculate parvocellular layers, show opponent responses sensitive to only mid and long wavelengths; no evidence of short-wavelength-sensitive cone (S-cone) input to any midget ganglion cell has been found. However, the small bistratified cells, which also project to the parvocellular geniculate layers, give a strong blue-ON response to stimuli designed to modulate S-cones. Thus, S-cone and medium- or long-wavelength-sensitive cone opponent signals arise from morphologically distinct ganglion cell types that project in parallel to the lateral geniculate nucleus.

Animals↗

The mosaic of midget ganglion cells in the human retina.

To study their detailed morphology, ganglion cells of the human retina were stained by intracellular tracer injection, in an in vitro, whole-mount preparation. This report focuses on the dendritic morphology and mosaic organization of the major, presumed color-opponent, ganglion cell class, the midget cells. Midget cells in the central retina were recognized by their extremely small dendritic trees, approximately 5-10 microns in diameter. Between 2 and 6 mm eccentricity, midget cells showed a steep, 10-fold increase in dendritic field size, followed by a more shallow, three- to fourfold increase in the retinal periphery, attaining a maximum diameter of approximately 225 microns. Despite large local variation in dendritic field size, midget cells formed one morphologically distinctive class at all retinal eccentricities. Two midget cell types were distinguished by their dendritic stratification in either the inner or outer portion of the inner plexiform layer (IPL), and presumably correspond to ON- and OFF-center cells respectively. The mosaic organization of the midget cells was examined by intracellularly filling neighboring cells in small patches of retina. For both the inner and outer midget populations, adjacent dendritic trees apposed one another but did not overlap, establishing a coverage of no greater than 1. The two mosaics differed in spatial scale, however: the outer midget cells showed smaller dendritic fields and higher cell density than the inner midget cells. An outer:inner cell density ratio of 1.7:1 was found in the retinal periphery. An estimate of total midget cell density suggested that the proportion of midget cells increases from about 45% of total ganglion cell density in the retinal periphery to about 95% in the central retina. Nyquist frequencies calculated from midget cell spacing closely match a recent measure of human achromatic spatial acuity (Anderson et al., 1991), from approximately 6 degrees to 55 degrees eccentricity. Outside the central retina, midget cell dendrites arborized in clusters within the overall dendritic field. With increasing eccentricity, the dendritic clusters increased in number and remained small (approximately 10-20 microns diameter) relative to the size of the dendritic field. Because neighboring midget cell dendritic trees do not overlap, the mosaic as a whole showed a pattern of clusters and holes. We hypothesize that midget cell dendritic trees may contact individual axon terminals of some midget bipolar cells and avoid contacting others, providing a basis for the formation of cone-specific connections in the IPL.

Color Perception↗

Dendritic field size and morphology of midget and parasol ganglion cells of the human retina.

The visual system of the macaque monkey has provided a useful model for understanding the neural basis of human vision, yet, there are few detailed comparisons of neural populations other than photoreceptors for the two species. Using intracellular staining in an in vitro preparation of the isolated and intact human retina, we have characterized the relationship of dendritic field size to retinal eccentricity for the two major ganglion cell classes, the midget and the parasol cells. We report three findings. (i) The difference in dendritic field diameter between the parasol and midget cells increases from a ratio of approximately 3:1 in the retinal periphery to approximately 10:1 at 3 degrees eccentricity, suggesting that human midget cells may outnumber parasol cells by as much as 30:1 in the central retina. (ii) The dendritic fields of human ON-center parasol and midget cells are 30-50% larger in diameter than their OFF-center counterparts, suggesting a distinct asymmetry in the human ON-OFF visual pathways. (iii) The dendritic fields of parasol cells, but not midget cells, are larger in humans than in macaques. The difference increases from approximately 20% in the retinal periphery to approximately 90% at 5 degrees eccentricity. This result predicts that the human parasol cells should show a lower resolving ability and an increased sensitivity to luminance contrast than their equivalents in the macaque.

Animals↗

The dopaminergic amacrine cell.

The detailed morphology of the dopaminergic amacrine cell type has been characterized in the macaque monkey retina by intracellular injection of horseradish peroxidase (HRP). This cell type was recognized by its large soma in an in vitro, wholemount preparation of the retina stained with the fluorescent dye, acridine orange. HRP-fills revealed a large, sparsely branching, spiny dendritic tree and a number of extremely thin, axon-like processes that arose from the soma and proximal dendrites. The axon-like processes were studded with distinct varicosities and were traced for up to 3 mm beyond the dendritic tree. The true lengths of the axon-like processes were greater than 3 mm, however, because the HRP reaction product consistently diminished before an endpoint was reached. Both the dendrites and the axon-like processes were narrowly stratified close to the outer border of the inner plexiform layer, although in a few cases single axon-like processes projected into the outer nuclear and outer plexiform layers. The HRP-filled amacrines appeared equivalent to a subpopulation of neurons that are intensely immunoreactive for tyrosine hydroxylase (TH). TH-immunoreactive cells showed a nearly identical soma size and dendritic field size range, the same pattern of dendritic branching and spiny morphology, and also gave rise to distinct axon-like processes from both the soma and proximal dendrites. To test this correspondence more directly, the large acridine stained cells were injected with Lucifer Yellow and the retina was subsequently processed for TH immunoreactivity using diaminobenzidine as the chromagen. In all cases Lucifer Yellow injected cells also showed intense TH immunoreactivity. Spatial densities of the TH amacrine cells were therefore used to calculate coverage factors for the dendritic trees and for the axon-like components of the HRP-filled cells. The axon-like processes showed a coverage factor of at least 300, about 100 times that of the dendritic fields. This great overlap could be directly observed in TH-immunoreacted retinal wholemounts as a dense plexus of fine, varicose processes. The density of the TH plexus is greater than the density predicted from the lengths (1-3 mm) of the HRP-filled axon-like processes however, and suggests that the axon-like processes have an actual length of about 4-5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Acridine Orange↗

Monoamine-accumulating ganglion cell type of the cat's retina.

A monoamine-accumulating ganglion cell type has been identified in an in vitro preparation of the cat's retina by a catecholamine-like fluorescence that appears following intravitreal injections of dopamine and the indoleaminergic transmitter analog, 5,7-dihydroxytryptamine (5,7-DHT). A subpopulation of large, weakly fluorescing neurons were identified as composing a single, morphologically distinct ganglion cell type by intracellular injections of horseradish peroxidase (HRP). In a sample of 374 HRP-filled cells soma diameter ranged from 13-21 microns (mean +/- SD = 16.6 +/- 1.3). Dendritic field size increased with increasing retinal eccentricity from 150-200 microns diameter at 0.5 mm from the area centralis to 600-800 microns diameter in the far retinal periphery. Dendrites are thin (approximately 1 micron diameter), show a characteristic branching pattern, and are narrowly stratified at the outer border of the inner plexiform layer. The monoamine-accumulating ganglion cell and the outer (OFF-center) alpha cell occupy distinct strata within sublamina a of the inner plexiform layer separated by a gap of about 5 microns. The total number of monoamine-accumulating (MA) ganglion cells was estimated at 5,400, about 3.5% of the total ganglion cell population. Spatial density of the MA ganglion cells, calculated from cell counts made in vitro, ranges from 60 cells/mm2 near the area centralis to 5 cells/mm2 in the far retinal periphery. A coverage factor (density x dendritic field area) of 2.2 was maintained from central to peripheral retina. The nature of the dendritic overlap was observed directly by making HRP injections into several neighboring ganglion cells. Five to seven neighboring dendritic trees extensively overlapped a given cell's dendritic field. However the dendritic processes did not intersect randomly but tended to interdigitate such that a uniform interdendritic spacing and density of dendritic processes was constructed locally within the dendritic plexus. Rotation of individual dendritic trees from their normal orientation produced a dramatic 4-5-fold increase in the number of dendritic intersections, suggesting that an active, local mechanism operates in the precise placement of individual dendrites within the plexus. The monoamine-accumulating ganglion cell appears morphologically equivalent to the delta ganglion cell (Boycott and Wässle; J. Physiol. (Lond.) 240:397-419, '74; Kolb et al.; Vision Res. 21:1081-1114, '81) and to the recently recognized indoleamine-accumulating ganglion cell (Wässle et al: J. Neurosci. 7:1574-1585, '87).(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗

Axon-bearing amacrine cells of the macaque monkey retina.

A new and remarkable type of amacrine cell has been identified in the primate retina. Application of the vital dye acridine orange to macaque retinas maintained in vitro produced a stable fluorescence in the somata of apparently all retinal neurons in both the inner nuclear and ganglion cell layers. Large somata (approximately 15-20 microns diam) were also consistently observed in the approximate center of the inner plexiform layer (IPL). Intracellular injections of horseradish peroxidase (HRP) made under direct microscopic control showed that the cells in the middle of the IPL constitute a single, morphologically distinct amacrine cell subpopulation. An unusual and characteristic feature of this cell type is the presence of multiple axons that arise from the dendritic tree and project beyond it to form a second, morphologically distinct arborization within the IPL; these cells have thus been referred to as axon-bearing amacrine cells. The dendritic tree of the axon-bearing amacrine cell is highly branched (approximately 40-50 terminal dendrites) and broadly stratified, spanning the central 50% of the IPL so that the soma is situated between the outermost and innermost branches. Dendritic field size increases from approximately 200 microns in diameter within 2 mm of the fovea to approximately 500 microns in the retinal periphery. HRP injections of groups of neighboring cells revealed a regular intercell spacing (approximately 200-300 microns in the retinal periphery), suggesting that dendritic territories uniformly cover the retina. One to four axons originate from the proximal dendrites as thin (less than 0.5 microns), smooth processes. The axons increase in diameter (approximately 1-2 microns) as they course beyond the dendritic field and bifurcate once or twice into secondary branches. These branches give rise to a number of thin, bouton-bearing collaterals that extend radially from the dendritic tree for 1-3 mm without much further branching. The result is a sparsely branched and widely spreading axonal tree that concentrically surrounds the smaller, more highly branched dendritic tree. The axonal tree is narrowly stratified over the central 10-20% of the IPL; it is approximately ten times the diameter of the dendritic tree, resulting in a 100 times greater coverage factor. The clear division of an amacrine cell's processes into distinct dendritic and axonal components has recently been observed in other, morphologically distinct amacrine cell types of the cat and monkey retina and therefore represents a property common to a number of functionally distinct cell types. It is hypothesized that the axon-bearing amacrine cells, like classical neurons,

Acridine Orange↗

Dopamine-accumulating retinal neurons revealed by in vitro fluorescence display a unique morphology.

Dopamine is the principal catecholamine neurotransmitter in the vertebrate retina. The shape of retinal neurons that accumulate dopamine has been demonstrated in an in vitro preparation of cat retina. This was achieved by the discovery that the combined uptake of dopamine and the indoleaminergic transmitter analog 5,7-dihydroxytryptamine leads to an intense, catecholamine-like fluorescence in the cell bodies and processes of presumed dopaminergic amacrine cells in the living retina. This fluorescence served as an in vitro marker for these cells, and their detailed morphology was analyzed after intracellular injection of horseradish peroxidase under direct microscopic control. The horseradish peroxidase-filled cells show an unprecedented neuronal morphology: each cell gives rise to multiple, axon-like processes that arise from, and extend for millimeters beyond, the dendritic tree. The unique structure of this type of amacrine cell suggests a function for dopamine in long-range lateral interactions in the inner plexiform layer.

Animals↗