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.     

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.     

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.     

Long-distance intraretinal connections in birds

Electrophysiological experiments have shown in both birds and mammals that remote parts of the retina, several millimetres apart, interact at the retinal level. The anatomical basis of this is poorly understood, although in mammals some cells in the ganglion cell layer have axons that terminate in the inner plexiform layer several millimetres from the cell body. In birds, the longest previously reported intraretinal connections were from amacrine cells, extending only a few hundred microns. But we here describe very long connections that span almost the entire extent of the retina in chicks and chick embryos. The parent cell bodies are in the inner nuclear layer of the ventral half of the retina, and they project in topographical order onto the dorsal half. They do not project to the brain. They may be involved in selective switching of attention between the upper and lower parts of the visual field, at an unprecedentedly early stage of visual processing.     

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.     

Effect of impulse blockage on cytochrome oxidase activity in monkey visual system

Cytochrome oxidase (cytochrome c oxidase; ferrocytochrome c: oxygen oxidoreductase, EC 1.9.2.1) has been introduced as an oxidative metabolic marker for neurones in the central nervous system. Previous studies have shown that mature neurones remained sensitive to altered functional demands, and that both developing and adult neurones responded to sensory deprivation or deafferentation by reducing their cytochrome oxidase (Cyt. Ox.) activity. More recently, we showed that the blockage of retinal impulse transmission with tetrodotoxin led to a reversible reduction in Cyt. Ox. staining of affected lateral geniculate (LGN) and striate neurones in adult cats. The present study sought to extend these findings to adult monkeys, where Cyt. Ox. 'puffs' or 'blobs' are uniquely present in the visual cortex. We found that, while the retina remained histologically intact, with only moderate decreases in Cyt. Ox. staining of large ganglion cells and the two plexiform layers, subtle changes occurred in the LGN as early as 1 day post-tetrodotoxin injection, and clear reduction in enzyme levels was evident in both the LGN and the visual cortex by 3 days. Changes became progressively more severe up to 4 weeks post-injection. Within area 17, alternating bands of high and low Cyt. Ox. staining occurred in lamina IV, with alternating rows of dark and lightly reactive puffs superimposed in exact register. Thus, the mature visual neurones in the primate remain extremely sensitive to the cessation of retinal impulse transmission, and plastic metabolic changes occur through several synapses along the sensory pathway.     

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     

Synaptic connectivity of a local circuit neurone in lateral geniculate nucleus of the cat

Although receptive fields of relay cells in the lateral geniculate nucleus of the cat nearly match those of their retinal afferents, only 10-20% of the synapses on these cells derive from the retina and are excitatory. Many more (30-40%) are inhibitory and largely control the gating of retinogeniculate transmission. These inhibitory synapses derive chiefly from two cell types: intrinsic local circuit neurones and cells in the adjacent perigeniculate nucleus. It has been difficult to study the functional organization of these inhibitory pathways; most efforts have relied on indirect approaches. Here we describe the use of direct techniques to study a local circuit neurone by iontophoresing horseradish peroxidase (HRP) into it, which completely labels the soma and processes of cells for subsequent light- and electron microscopic analysis. Although the response properties of the labelled cell are virtually indistinguishable from those of many relay cells, its morphology is typical of 'class 3' neurones (see Fig. 1 legend), which are widely believed to be interneurones (but see ref. 12). Here, we refer to the cell as a 'local circuit neurone', which allows for the possibility of a projection axon, rather than as an 'interneurone', a term that commonly excludes a projection axon. We find that the labelled cell has a myelinated axon, but that the axon loses its myelin within 50 microns of the soma and has not yet been traced further. The dendrites of the labelled cell possess presynaptic terminals that act as intrinsic sources of inhibition on geniculate relay cells. We also characterize other morphological aspects of this inhibitory circuitry.     

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.     

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.     

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.     

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.     

初孵扬子鳄大脑皮层组织学结构观察

本文用光镜对扬子鳄大脑皮层的组织学结构进行了研究 .扬子鳄大脑皮层可分为外网状层、细胞层和内网状层三层 ,神经细胞绝大多数集中于细胞层内 ,内、外网状层中零星分布一些小细胞 .从内侧到外侧 ,大脑皮层可分为海马、新皮质和梨状皮质三部分 ,三者之间无明显界线 ,细胞排布有所区别 .本文对扬子鳄的大脑皮层同其他脊椎动物的进行了比较讨论 .     

ATP excites a subpopulation of rat dorsal horn neurones

The peripheral receptive properties and central projections of different classes of dorsal root ganglion neurones are well characterized. Much less is known about the transmitters used by these neurones. Excitatory amino acids have been proposed as sensory transmitters but the sensitivity of virtually all central neurones to those compounds has made it difficult to assess their precise role in sensory transmission. Several neuropeptides have been localized within discrete subclasses of primary sensory neurones that project to the superficial dorsal horn of the spinal cord and may be afferent transmitters. However, only about one-third of spinal sensory neurones have been shown to contain neuropeptides. We have recently described the presence of a 5'-nucleotide hydrolysing acid phosphatase in a separate subpopulation of dorsal root ganglion neurones that project to the superficial dorsal horn. This enzyme also appears in certain autonomic and endocrine cells that contain high concentrations of releasable nucleotides in their storage granules. It is possible that the presence of this enzyme in sensory neurones is also associated with a releasable pool of nucleotides. Holton and Holton have provided evidence that ATP is released from the peripheral terminals of unmyelinated sensory fibres and have suggested that release of ATP might also occur from central sensory terminals. To investigate the possibility that nucleotides act as central sensory transmitters we have examined their actions on rat dorsal horn and dorsal root ganglion neurones maintained in dissociated cell culture. We report here a selective and potent excitation of subpopulations of both neuronal types by ATP.     

A cell surface molecule distributed in a dorsoventral gradient in the perinatal rat retina

Brain topography may have its earliest expression as spatial gradients of molecules controlling the deposition of neurones and neuronal processes. In the vertebrate visual system there is evidence that the stereotyped alignment of central retinal projections relies on an initial spatially organized distribution of molecules in both the retina and its central target nuclei. We used an immunological approach to look for molecules that are so organized and produced a monoclonal antibody (JONES) which shows a pronounced dorsal to ventral gradient of binding in the rat retina throughout the period when retinal ganglion cell axons are forming topographically organized projections within the central nervous system (CNS). Binding is present throughout the radial thickness of the retinal epithelium in regions where postmitotic neurones are generated but is not associated with any consistent histological characteristic of the tissue. The antibody was shown to bind on the cell surface of freshly dissociated retinal cells, and dorsal retinal quadrants were found in vitro to have nearly twice as much antigen as ventral retinal quadrants. Initial biochemical characterization of the target epitope reveals that it is a lipid present in chloroform/methanol extracts from perinatal retina and is sensitive to neuraminidase digestion.     

Rapid BDNF-induced retrograde synaptic modification in a developing retinotectal system

In cultures of hippocampal neurons, induction of long-term synaptic potentiation or depression by repetitive synaptic activity is accompanied by a retrograde spread of potentiation or depression, respectively, from the site of induction at the axonal outputs to the input synapses on the dendrites of the presynaptic neuron. We report here that rapid retrograde synaptic modification also exists in an intact developing retinotectal system. Local application of brain-derived neurotrophic factor (BDNF) to the Xenopus laevis optic tectum, which induced persistent potentiation of retinotectal synapses, led to a rapid modification of synaptic inputs at the dendrites of retinal ganglion cells (RGCs), as shown by a persistent enhancement of light-evoked excitatory synaptic currents and spiking activity of RGCs. This retrograde effect required TrkB receptor activation, phospholipase Cgamma activity and Ca2+ elevation in RGCs, and was accounted for by a selective increase in the number of postsynaptic AMPA-subtype glutamate receptors at RGC dendrites. Such retrograde information flow in the neuron allows rapid regulation of synaptic inputs at the dendrite in accordance to signals received at axon terminals, a process reminiscent of back-propagation algorithm for learning in neural networks.     

Elimination of action potentials blocks the structural development of retinogeniculate synapses

Although the influence of electrical activity on neural development has been studied extensively, experiments have only recently focused on the role of activity in the development of the mammalian central nervous system (CNS). Using tetrodotoxin (TTX) to abolish sodium-mediated action potentials, studies on the visual system show that impulse activity is essential both for the normal development of neuronal size and responsivity in the lateral geniculate nucleus (LGN), and for the eye-specific segregation of geniculo-cortical axons. There have been no anatomical studies to investigate the influence of action potentials on CNS synaptic development. We report here the first direct evidence that elimination of action potentials in the mammalian CNS blocks the growth of developing axon terminals and the formation of normal adult synaptic patterns. Our results show that when TTX is used to eliminate retinal ganglion-cell action potentials in the cat from birth to 8 weeks, the connections made by ganglion cell axons with LGN neurones, retinogeniculate synapses, remain almost identical morphologically to those in the newborn kitten.     

An opiate system in the goldfish retina

Recently, in addition to conventional neurotransmitters such as acetylcholine, dopamine, glycine and gamma-aminobutyric acid (GABA), putative neuroactive peptide transmitters have been localized to specific retinal amacrine cells. In particular, opiate receptors 2,3, assayable enkephalin immunoreactivity and enkephalin-immunoreactive neurones 1,5 have been described in avian and mammalian retinae. However, little physiological evidence has been obtained for the involvement of neuropeptides in retinal function. Here we report that exogenous opiates affect both the release of GABA from GABAergic amacrine cells and the firing patterns of ganglion cells in the goldfish retina. Our results show that the output of the retina is modulated by an opiate system whose neural organization and pharmacological properties resemble those described elsewhere in the vertebrate central nervous system.     

Retinal ganglion cells lose response to laminin with maturation

The decisive role played by adhesive interactions between neuronal processes and the culture substrate in determining the form and extent of neurite outgrowth in vitro has greatly influenced ideas about the mechanisms of axonal growth and guidance in the vertebrate nervous system. These studies have also helped to identify adhesive molecules that might be involved in guiding axonal growth in vivo. One candidate molecule is laminin, a major glycoprotein of basal laminae which has been shown to induce a wide variety of embryonic neurones to extend neurites in culture. Moreover, laminin is found in large amounts in injured nerves that can successfully regenerate but is absent from nerves where regeneration fails. However, it is unclear to what extent the mechanisms that regulate axonal regeneration also operate in the embryo when axon outgrowth is initiated. Here we have examined the substrate requirements for neurite outgrowth in vitro by chick embryo retinal ganglion cells, the only cells in the retina to send axons to the brain. We show that while retinal ganglion cells from embryonic day 6 (E6) chicks extend profuse neurites on laminin, those from E11 do not, although they retain the ability to extend neurites on astrocytes via a laminin-independent mechanism. This represents the first evidence that central nervous system neurones may undergo a change in their substrate requirements for neurite outgrowth as they mature.