Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina

The development of orderly connections in the mammalian visual system depends on action potentials in the optic nerve fibers, even before the retina receives visual input. In particular, it has been suggested that correlated firing of retinal ganglion cells in the same eye directs the segregation of their synaptic terminals into eye-specific layers within the lateral geniculate nucleus. Such correlations in electrical activity were found by simultaneous recording of the extracellular action potentials of up to 100 ganglion cells in the isolated retina of the newborn ferret and the fetal cat. These neurons fired spikes in nearly synchronous bursts lasting a few seconds and separated by 1 to 2 minutes of silence. Individual bursts consisted of a wave of excitation, several hundred micrometers wide, sweeping across the retina at about 100 micrometers per second. These concerted firing patterns have the appropriate spatial and temporal properties to guide the refinement of connections between the retina and the lateral geniculate nucleus.     

The nasotemporal division in primate retina: the neural bases of macular sparing and splitting

In primates, each hemisphere contains a representation of the contralateral visual hemifield; unilateral damage to the visual pathways results in loss of vision in half of the visual field. Apparently similar severe, unilateral lesions to the central visual pathways can result in two qualitatively different central visual field defects termed macular sparing and macular splitting. In macular sparing a 2 degrees to 3 degrees region around the fovea is spared from the effects of unilateral damage to the visual pathways. In macular splitting there is no such spared region and the scotoma produced by unilateral brain damage bisects the fovea. The patterns of decussation of the different classes of retinal ganglion cells in both New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have been determined by horseradish peroxidase injection. In both species the distributions of ipsilaterally and contralaterally projecting ganglion cells in the central retina are different from those in other mammals and suggest neural bases for macular sparing and splitting, respectively.     

Hyperacuity in cat retinal ganglion cells

Cat X retinal ganglion cells that can resolve sine gratings of only 2.5 cycles per degree can nevertheless respond reliably to displacements of a grating of approximately 1 minute of arc. This is a form of hyperacuity comparable in magnitude to that seen in human vision. A theoretical analysis of this form of hyperacuity reveals it to be a result of the high gain and low noise of ganglion cells. The hyperacuity expected for the best retinal ganglion cells is substantially better than that observed in behavioral experiments. Thus the brain, rather than improving on the retinal signal-to-noise ratio by pooling signals from many ganglion cells, is unable to make use of all the hyperacuity information present in single ganglion cell responses.     

Formation of retinal ganglion cell topography during prenatal development

A fundamental feature of the mammalian visual system is the nonuniform distribution of ganglion cells across the retinal surface. To understand the ontogenetic processes leading to the formation of retinal ganglion cell topography, changes in the regional density of these neurons were studied in relation to ganglion cell loss and the pattern of retinal growth in the fetal cat. Midway through the gestation period, the density of these neurons was only two to three times greater in the area centralis than in the peripheral retina, whereas shortly before birth this central-to-peripheral difference was nearly 20-fold. Age-related changes in the ganglion cell distribution were found not to correspond in time or magnitude to the massive loss of ganglion cells that occurs during prenatal development. Rather, the formation of ganglion cell density gradients can be accounted for by unequal expansion of the growing fetal retina-peripheral regions expand more than the central region, thereby diluting the peripheral density of ganglion cells to a greater degree. Nonuniform growth, in conjunction with differential periods of neurogenesis of the different types of retinal cells, appears to be a dominant factor regulating overall retinal topography. These results suggest that the differential regional expansion of the fetal retina underlies the formation of magnification factors in the developing visual system.     

Dendritic-tree anatomy codes form-vision physiology in tadpole retina

In tadpole frog retina, the development of four classes of visual form detectors matched the growth of four types of ganglion cell dendritic trees. From this correlation of electrophysiology and anatomy we concluded that the structure of retinal ganglion cell dendritic trees provides the code for detection of visual shapes.     

Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture

Functional nicotinic cholinergic receptors are found on mammalian retinal ganglion cell neurons in culture. The neurotransmitter acetylcholine (ACh) can be detected in the medium of many of these retinal cultures, after release presumably from the choline acetyltransferase-positive amacrine cells. The postsynaptic effect of endogenous or applied ACh on the ganglion cells can be blocked with specific nicotinic antagonists. Here it is shown that within 24 hours of producing such a pharmacologic blockade, the retinal ganglion cells begin to sprout or regenerate neuronal processes. Thus, the growth-enhancing effect of nicotinic antagonists may be due to the removal of inhibition to growth by tonic levels of ACh present in the culture medium. Since there is a spontaneous leak of ACh in the intact retina, the effects of nicotinic cholinergic drugs on process outgrowth in culture may reflect a normal control mechanism for growth or regeneration of retinal ganglion cell processes that is exerted by ACh in vivo.     

Corresponding spatial gradients of TOP molecules in the developing retina and optic tectum

The topographic map of cell position in the avian retina is inverted in its projection to the optic tectum. Dorsal retinal ganglion cell axons project to ventral tectum, and ventral retinal ganglion cells project to dorsal tectum. Topographic gradients of toponymic (TOP) cell surface molecules along the dorsoventral axes of retina and tectum also are inverted. TOP molecules are most abundant in dorsal retina and ventral tectum and least abundant in ventral retina and dorsal tectum during the period of initial retinal-tectal interaction. Thus, TOP molecules may be involved in orienting the retinotectal map.     

Direction-selective units in rabbit retina: distribution of preferred directions

The preferred directions of 102 direction-selective ganglion cells in the rabbit retina have been determined. Cells of the "on-off" type form four nonoverlapping groups; cells of the "on" type fall into three groups. The on-off groups appear to correspond to the directions of apparent object displacement produced by contractions of the four rectus muscles. Each group of cells could, without further processing, provide the error signal for a visual servo-systerm minimizing retinal image motion.     

GDF11 controls the timing of progenitor cell competence in developing retina

The orderly generation of cell types in the developing retina is thought to be regulated by changes in the competence of multipotent progenitors. Here, we show that a secreted factor, growth and differentiation factor 11 (GDF11), controls the numbers of retinal ganglion cells (RGCs), as well as amacrine and photoreceptor cells, that form during development. GDF11 does not affect proliferation of progenitors-a major mode of GDF11 action in other tissues-but instead controls duration of expression of Math5, a gene that confers competence for RGC genesis, in progenitor cells. Thus, GDF11 governs the temporal windows during which multipotent progenitors retain competence to produce distinct neural progeny.     

Spontaneous impulse activity of rat retinal ganglion cells in prenatal life

The existence of spontaneous neural activity in mammalian retinal ganglion cells during prenatal life has long been suspected. This activity could play a key role in the refinement of retinal projections during development. Recordings in vivo from the retinas of rat fetuses between embryonic day 17 and 21 found action potentials in spontaneously active ganglion cells at all the ages studied.     

Eye-specific retinogeniculate segregation independent of normal neuronal activity

The segregation of initially intermingled left and right eye inputs to the dorsal lateral geniculate nucleus (DLGN) during development is thought to be in response to precise spatial and temporal patterns of spontaneous ganglion cell activity. To test this hypothesis, we disrupted the correlated activity of neighboring ganglion cells in the developing ferret retina through immunotoxin depletion of starburst amacrine cells. Despite the absence of this type of correlated activity, left and right eye inputs segregated normally in the DLGN. By contrast, when all spontaneous activity was blocked, the projections from the two eyes remained intermingled. Thus, certain features of normal neural activity patterns are not required for the formation of eye-specific projections to the DLGN.     

Lateral interactions at inner plexiform layer of vertebrate retina: antagonistic responses to change

Lateral interactions at the inner plexiform layer of the retina of the mudpuppy were studied intracellularly after they were isolated from interactions at the outer plexiform layer with a special stimulus. The isolation was confirmed by recording no surround effect at bipolar cells under conditions that elicited a strong surround effect at ganglion cells. It appears that amacrine cell, which respond to spatiotemporal change at one retinal region, inhibit the response to change in on-off ganglion cells at adjacent sites.     

Distribution of cones in human and monkey retina: individual variability and radial asymmetry

The distribution of photoreceptors is known for only one complete human retina and for the cardinal meridians only in the macaque monkey retina. Cones can be mapped in computer-reconstructed whole mounts of human and monkey retina. A 2.9-fold range in maximum cone density in the foveas of young adult human eyes may contribute to individual differences in acuity. Cone distribution is radially asymmetrical about the fovea in both species, as previously described for the distribution of retinal ganglion cells and for lines of visual isosensitivity. Cone density was greater in the nasal than in the temporal peripheral retina, and this nasotemporal asymmetry was more pronounced in monkey than in human retina.     

Receptive fields in the cat retina: a new type

A new type of receptive field of cat retinal ganglion cells is described and termed the "suppressed-by-contrast" type. The firing rate of these cells is suppressed by a variety of visual stimuli. However, it has not been possible to find a stimulus that increases the firing rate above the maintained level.     

Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells

The central nervous system (CNS) loses the ability to regenerate early during development, but it is not known why. The retina has long served as a simple model system for study of CNS regeneration. Here we show that amacrine cells signal neonatal rat retinal ganglion cells (RGCs) to undergo a profound and apparently irreversible loss of intrinsic axon growth ability. Concurrently, retinal maturation triggers RGCs to greatly increase their dendritic growth ability. These results suggest that adult CNS neurons fail to regenerate not only because of CNS glial inhibition but also because of a loss of intrinsic axon growth ability.     

Transient morphological features of identified ganglion cells in living fetal and neonatal retina

The function and morphology of retinal ganglion cells in the adult mammalian visual system has been well studied, but little is known about how the adult state is achieved. To address this question, the morphological changes that retinal ganglion cells undergo during development were studied. Ganglion cells were first identified by retrograde labeling with rhodamine latex microspheres deposited in retinorecipient targets in fetal and early postnatal cats. The structure of ganglion cells was then revealed by intracellular injection of Lucifer yellow in living retinas removed and maintained in vitro. As early as 2 weeks before birth, a morphologically diverse assortment of ganglion cells is present, some of which resemble the alpha, beta, and gamma classes found in the adult. However, in contrast to the adult, developing ganglion cells exhibit several transient features, including excessive axonal and dendritic branching and exuberant somatic and dendritic spines. These morphological features indicate that there is a transient network of connectivity that could play an important role in the final determination of retinal ganglion cell form and function.     

Centrifugal effects in the avian retina

Electrical stimulation of the centrifugal fibers to the avian retina can disturb the balance between the excitatory and inhibitory system within the receptive fields of individual retinal ganglion cells. Although the mechanisms may vary from one unit to another, the effect is always to make them fire more readily and to a wider range of visual inputs.     

Synaptic connections of the centrifugal fibers in the pigeon retina

The centrifugal fibers in the pigeon retina end in the inner nuclear layer and form two kinds of terminals, convergent and divergent. In the inner nuclear layer the fibers synapse with amnacrine and displaced ganglion cells. Because of their great number and their even distribution these fibers appear to constitute a system for the localized centrifugal control of the retinal functions.     

Seeing more clearly: recent advances in understanding retinal circuitry

Among 10 breakthroughs that Science announced at the end of 2002 was the discovery of a photosensing (melanopsin-containing) retinal ganglion cell (RGC) and its role in entraining the circadian clock. This breakthrough exemplifies the ultimate goal of neuroscience: to understand the nervous system from molecules to behavior. Light-sensing RGCs constitute one of a dozen discrete RGC populations coding various aspects of visual scenes by virtue of their unique morphology, physiology, and coverage of the retina. Interestingly, the function of the melanopsin-containing RGCs in entraining the circadian clock need not involve much retinal processing, making it the simplest form of processing in the retina. This review focuses on recent advances in our understanding of retinal circuitry, visual processing, and retinal development demonstrated by innovative experimental techniques. It also discusses the advantages of using the retina as a model system to address some of the key questions in neuroscience.     

Conduction velocity variations minimize conduction time differences among retinal ganglion cell axons

The visual system is able to accurately represent the spatiotemporal relations among the elements of a changing visual scene as the image moves across the retinal surface. This precise spatiotemporal mapping occurs despite great variability in retinal position and conduction velocity even among retinal ganglion cells of the same physiological class-a variability that would seem to reduce the precision with which spatiotemporal information can be transmitted to central visual areas. There was a strong negative relation between the intraretinal and extraretinal conduction time for axons of individual ganglion cells of the X-cell class. The effect of this relation was to produce a nearly constant total transmission time between the soma of a retinal X cell and its central target site. Thus, the variation in the conduction velocities of retinal ganglion cell axons may ensure that, regardless of the constraints imposed by retinal topography, a precise spatiotemporal central representation of the retinal image is maintained.