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.     

Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina

In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL), a laminar region that is conventionally divided into five major parallel sublaminae. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs) and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo for the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes.     

乌梢蛇视网膜的显微结构观察

采用光镜观察了乌梢蛇(Zoacys dhumnades)视网膜的结构,测量并比较了外核层、内核层与节细胞层的细胞数量,分析了视细胞的分布特征,研究了其视网膜结构与生活习性的关系.结果表明,乌梢蛇视网膜中央区分布着大量的视锥细胞,外核层与节细胞层的细胞数量相当,色素上皮层的细胞有许多突起伸向视杆视锥层内,说明乌梢蛇是一种昼行性蛇类.视网膜盲部接近视部处有椭圆形突起,该突起呈连续分布而形成一圈,突起内可见血窦及丰富的红细胞,该突起可能与锥状突和/或栉膜具有同源关系.     

Substance P-immunoreactive retinal ganglion cells and their central axon terminals in the rabbit

Retinal ganglion cells are the projection neurons that link the retina to the brain. Peptide immunoreactive cells in the ganglion cell layer (GCL) of the mammalian retina have been noted but their identity has not been determined. We now report that, in the rabbit, 25-35% of all retinal ganglion cells contain substance P-like (SP) immunoreactivity. They were identified by either retrograde transport of fluorescent tracers injected into the superior colliculus, or by retrograde degeneration after optic nerve section. SP immunoreactive cells are present in all parts of the retina and have medium to large cell bodies with dendrites that ramify extensively in the proximal inner plexiform layer. Their axons terminate in the dorsal lateral geniculate nucleus, superior colliculus and accessory optic nuclei, and these terminals disappear completely after contralateral optic nerve section and/or eye enucleation. In the dorsal lateral geniculate nucleus large, beaded, immunoreactive axons and varicosities make up a narrow plexus just below the optic tract, where they define a new geniculate lamina. The varicosities make multiple synaptic contacts with dendrites of dorsal lateral geniculate nucleus projection neurons and presumptive interneurons in complex glomerular neuropil. This is direct evidence that some mammalian retinal ganglion cells contain substance P-like peptides and strongly suggests that, in the rabbit, substance P (or related tachykinins) may be a transmitter or modulator in a specific population or populations of retinal ganglion cells.     

Two types of orientation-sensitive responses of amacrine cells in the mammalian retina.

Neurons sensitive to the orientation of light stimuli exist throughout the mammalian visual system, suggesting that this spatial feature is a fundamental cue used by the brain to decipher visual information. The most peripheral neurons known to show orientation sensitivity are the retinal ganglion cells. Considerable morphological and pharmacological data suggest that the orientation sensitivity of ganglion cells is formed, at least partly, by the amacrine cells, which are laterally oriented interneurons presynaptic to the ganglion cells in the inner plexiform layer. So far there have been few studies of the responses of amacrine cells to oriented visual stimuli and their role in forming orientation-sensitive responses in the retina remains unclear. Here I report the novel finding of a population of amacrine cells in the rabbit retina which are orientation-sensitive. These amacrine cells can be divided into two subtypes, whose orientation sensitivity is manufactured by two distinct mechanisms. The orientation sensitivity of the first subtype of amacrine cell is formed from the interactions of excitatory, centre-receptive field synaptic inputs and inhibitory inputs of opposite polarity, whereas that for cells of the second subtype seems to be the product of a marked asymmetry in their dendritic arbors.     

Saccadic oscillations facilitate ocular perfusion from the avian pecten

THE evolution of the eye is constrained by two conflicting requirements--good vascular perfusion of the retina, and an optical path through the retina that is unobstructed by blood vessels. Birds are interesting in that they have higher metabolic rates and thicker retinas than mammals, but have no retinal blood vessels. Nutrients and oxygen must thus reach the neurons of the inner retina either from the choroid through 300 micron of metabolically very active retina, or from the pecten, a pleated vascular structure protruding from the head of the optic nerve into the vitreous chamber, and more than a centimetre away from some retinal neurons. Despite the diffusional distance involved, several lines of evidence indicate that the pecten is the primary source of nutrients for the inner retina: the presence of an oxygen gradient from pecten to retina, the large surface area produced by macroscopic folds and by microscopic infoldings of the luminal and external surfaces of the capillary endothelium, extrusion of circulating fluorescein, high content of carbonic anhydrase and alkaline phosphatase, and retinal impairments after pecten ablation. Another peculiarity of birds, their saccadic oscillations, occur with a large cyclotor-sional component during every saccadic eye movement. In different species, saccades, which occur at intervals of 0.5-40 s, have up to 13 oscillations with frequencies of 15-30 Hz and ampliá-tudes of about 10 degrees. Therefore, as much as 12% of some birds' total viewing time may be subject to the image instability caused by the oscillations. Using fluorescein angiography, we show here that during every saccade, the pecten acts as an agitator which propels perfusate towards the central retina much more effectively than is observed during intersaccadic intervals.     

Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina

Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them. These lamina-specific circuits determine the visual features to which RGC subtypes respond. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2 (ref. 10)--are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.     

大鼠不完全性视网膜缺血的组织学变化

采用双侧颈总动脉阻断血流（２ＶＯ）的方法，造成大鼠不完全性视网膜缺血，用组织学方法观察了不同缺血时间（３０、９０ｍｉｎ，４、７、３０ｄ）的缺血后再灌注与不再灌流对视网膜变化的影响。结果显示：缺血３０和９０ｍｉｎ再灌流４ｄ后，内炕网膜（包括外网层、内核层、内网层、节细胞层、神经纤维怪和内界膜）明显增厚；其他不再灌流的缺血组，厚度趋向减少。节细胞计数随缺血时间延长逐渐减少；缺血４ｄ后明显减少。提示不完     

Low retinal noise in animals with low body temperature allows high visual sensitivity

The weakest pulse of light a human can detect sends about 100 photons through the pupil and produces 10-20 rhodopsin isomerizations in a small retinal area. It has been postulated that we cannot see single photons because of a retinal noise arising from randomly occurring thermal isomerizations. Direct recordings have since demonstrated the existence of electrical 'dark' rod events indistinguishable from photoisomerization signals. Their mean rate of occurrence is roughly consistent with the 'dark light' in psychophysical threshold experiments, and their thermal parameters justify an identification with thermal isomerizations. In the retina of amphibians, a small proportion of sensitive ganglion cells have a performance-limiting noise that is low enough to be well accounted for by these events. Here we study the performance of dark-adapted toads and frogs and show that the performance limit of visually guided behaviour is also set by thermal isomerizations. As visual sensitivity limited by thermal events should rise when the temperature falls, poikilothermous vertebrates living at low temperatures should then reach light sensitivities unattainable by mammals and birds with optical factors equal. Comparison of different species at different temperatures shows a correlation between absolute threshold intensities and estimated thermal isomerization rates in the retina.     

Ganglion cell dendrites are presynaptic in catfish retina

The retinal ganglion cells are third-order, spike-generating neurones whose axons transmit the output of the retina to the rest of the brain. It has long been believed that the dendrites of the retinal ganglion cells, like the dendrites of most other Golgi type I neurones, are only postsynaptic. Here we have studied the synapses made onto the ganglion cells in the catfish (Ictalurus punctatus), and we report that the distal dendrites of large-field ganglion cells make conventional chemical synapses onto other inner plexiform layer processes. We have also found that, more than 100 microns away from the cell perikaryon, the synapses made onto and by these ganglion cell dendrites are often tightly clustered. These synaptic clusters appear to be quite regularly spaced along the dendrites. Our results have important implications for the identification of ganglion cell dendrites within the inner plexiform layer as well as for the understanding of the ganglion cell response and receptive field generation.     

Horizontal cell synapses onto glycine-accumulating interplexiform cells

Horizontal cells mediate lateral transmission of signals in the outer plexiform layer of the vertebrate retina, and are presumed to contribute to surround properties of photoreceptors and bipolar cells by chemical transmission. The cell bodies and dendrites of fish horizontal cells possess presynaptic specializations characteristic of conventional chemical synapses. Horizontal cell axon terminals have not so far been shown to contain presynaptic specializations nor have the targets of the somatic and dendritic synapses been fully characterized. Using electron microscope autoradiography of retinas labelled by high-affinity 3H-glycine uptake, we show here that goldfish horizontal cells make somatodendritic and axodendritic synapses on glycinergic interplexiform cells (Gly-IPCs) as apposed to dopaminergic interplexiform cells. Thus, horizontal cells have at least three postsynaptic targets: photoreceptors, bipolar cells and Gly-IPCs. Gly-IPCs may constitute a major alternative pathway for horizontal cell signals to reach the inner plexiform layer.     

Centrifugal fibres synapse on dopaminergic interplexiform cells in the teleost retina

In teleost fish, centrifugal fibres originating in the olfactory bulb and containing FMRFamide-like and luteinizing hormone releasing hormone (LHRH)-like peptides project to the retina and terminate along the border of the inner nuclear and inner plexiform layers. Using a novel simultaneous two-colour immunolabelling technique, we have found that these centrifugal fibres are often closely apposed to the dopaminergic interplexiform cells. Contacts between centrifugal fibres and dopaminergic interplexiform cells were observed by electron microscopy to be conventional type synaptic junctions. Since the dopaminergic interplexiform cells make synapses on horizontal and bipolar cells, providing an intraretinal centrifugal pathway for information flow from the inner to the outer plexiform layers, we conclude that every neuron in the teleost retina is potentially susceptible to central influences via these centrifugal fibres and dopaminergic interplexiform cells.     

Cortical magnification factor and the ganglion cell density of the primate retina

It has long been contentious whether the large representation of the fovea in the primate visual cortex (V1) indicates a selective magnification of this part of the retina, or whether it merely reflects the density of retinal ganglion cells. The measurement of the retinal ganglion-cell density is complicated by lateral displacements of cells around the fovea and the presence of displaced amacrine cells in the ganglion cell layer. We have now identified displaced amacrine cells by GABA immunohistochemistry and by retrograde degeneration of ganglion cells. By reconstructing the fovea from serial sections, we were able to compare the densities of cones, cone pedicles and ganglion cells; in this way we found that there are more than three ganglion cells per foveal cone. Between the central and the peripheral retina, the ganglion cell density changes by a factor of 1,000-2,000, which is within the range of estimates of the cortical magnification factor. There is therefore no need to postulate a selective magnification of the fovea in the geniculate and/or the visual cortex.     

Vertical interactions across ten parallel, stacked representations in the mammalian retina

The mammalian visual system analyses the world through a set of separate spatio-temporal channels. The organization of these channels begins in the retina, where the precise laminations of both the axon terminals of bipolar cells and the dendritic arborizations of ganglion cells suggests the presence of a vertical stack of neural strata at the inner plexiform layer (IPL). Conversely, many inhibitory amacrine cell classes are multiply or diffusely stratified, indicating that they might convey information between strata. On the basis of the diverse stratification and physiological properties of ganglion cells, it was suggested that the IPL contains a parallel set of representations of the visual world embodied in the strata and conveyed to higher centres by the classes of ganglion cells whose dendrites ramify at that stratum. Here we show that each stratum receives unique and substantively different excitatory and inhibitory neural inputs that are integrated to form at least ten different, parallel space-time spiking outputs. The response properties of these strata are ordered in the time domain. Inhibition through GABAC receptors extracts spatial edges in neural representations and seems to separate the functional properties of the strata. We describe a new form of neuronal interaction that we call 'vertical inhibition' that acts not laterally, but between strata.     

Novel pathway connecting the outer and inner vertebrate retina

In many fish retinas, thin axons from the external horizontal cells extend through the inner nuclear layer and expand into large terminal processes that lie along the border of the inner nuclear and inner plexiform layers. Although the horizontal-cell axon terminals are structurally very prominent, their function is unknown. Here we report morphological and functional evidence that signals from catfish (Ictalurus punctatus) horizontal-cell axon terminals can be transmitted directly to amacrine cells. Current injected into horizontal-cell axon terminals produces responses from both transient and sustained amacrine cells very similar to those elicited by light stimuli. Electron microscope observations show chemical synapses from the axon terminals onto amacrine cell perikarya and processes. These data suggest that amacrine cells in the catfish retina receive two inputs, one from bipolar cells and the other from horizontal-cell axon terminals.     

Retinal astrocytes are immigrants from the optic nerve

The retina in most mammals contains two types of macroglial cells--Müller cells, which span the entire thickness of the retina, and astrocytes, which are mainly confined to the nerve fibre layer. Whereas Müller cells are diffusely distributed in all vertebrate retinae, the presence and distribution of retinal astrocytes correlate with the presence and distribution of retinal blood vessels: retinae that are avascular contain no astrocytes; those that are diffusely vascularized contain diffusely distributed astrocytes; and those that are vascularized in a restricted region contain astrocytes only in the vascularized region. This striking correlation between vascularization and the presence of astrocytes led Stone and Dreher to postulate that retinal astrocytes are immigrants that enter the retina with its vasculature, although others have suggested that they derive from Müller cells. Here we provide strong evidence that astrocytes in the diffusely vascularized rat retina are immigrants from the optic nerve.     

Generation of end-inhibition in the visual cortex via interlaminar connections

To understand the mechanisms by which the receptive field properties of visual cortical cells are generated, one must consider both the thalamic input to the cortex and the intrinsic cortical connections. In the cat striate cortex, layer 4 is the main recipient of input from the lateral geniculate nucleus, yet the cells in that layer possess several receptive field properties that are distinct from the geniculate input, including orientation specificity, binocularity, directionality and end-inhibition, the last of which allows cells to respond to edges of a restricted length. These properties could be generated by connections within the layer, by its input from the claustrum or by the massive projection that layer 4 receives from layer 6. In the present study, we attempted to determine the functional role of the layer 6 to layer 4 projection by reversible inactivation of layer 6 using the inhibitory transmitter gamma-aminobutyric acid (GABA). After inactivating layer 6, cells in layer 4 lost end-inhibition. Cells in layer 2 + 3, which receive their principal input from layer 4, were similarly affected. The elimination of end-inhibition was specific, other receptive field properties, such as direction selectivity or orientation specificity, remaining intact.     

GAP-43在锦鲤荒漠沙蜥和雉鸡视网膜内分布的免疫组化研究

GAP-43具有多种功能,主要与神经元轴突的生长、再生、神经递质的释放及膜泡的吞噬有关.本研究用免疫组织化学的方法观察了正常成年锦鲤、荒漠沙蜥和雉鸡视网膜内GAP-43分布.结果显示GAP-43主要分布在内网层,另外,在内核层、外网层、光感受器细胞层因动物不同也呈现不同的分布特点,而在节细胞层中3种动物均未发现GAP-43阳性染色.在锦鲤视网膜中GAP-43主要分布在内网层和内核层的无长突细胞;在荒漠沙蜥视网膜中GAP-43主要分布在内网层和外网层,在雉鸡视网膜中GAP-43主要分布在内网层、外网层、外核层和光感受器外节,其中在雉鸡视网膜外核层和光感受器外节中发现阳性分布是在脊椎动物此层发现GAP-43的首次报道.     

Bipolar cells in the mudpuppy retina use an excitatory amino acid neurotransmitter

The bipolar cells of the vertebrate retina are the principal neuronal elements which transmit photoreceptor activity from the outer to the inner retina. An important function of the bipolars is to segregate photoreceptor input into independent ON and OFF channels which are subserved, respectively, by the depolarizing and hyperpolarizing bipolar subtypes. Ultrastructural and physiological observations suggest that chemical neurotransmission is the predominant means of bipolar input to the inner retina. Both ON and OFF bipolars apparently release excitatory transmitters. Histological studies with cytotoxic agents and physiological studies indicate that third-order neurones have excitatory amino acid receptors. In ON-OFF amacrine and ganglion cells, which receive input from both bipolars, ON and OFF excitation have a similar ionic basis, suggesting that the same transmitter may be released by both types of bipolars. We have now found that (+/-)cis-2,3-piperidine dicarboxylic acid (PDA), a new excitatory amino acid antagonist, blocks bipolar input to the inner retina and thus suggests that an excitatory amino acid is a bipolar cell transmitter.