A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina

2003 ◽  
Vol 20 (6) ◽  
pp. 589-600 ◽  
Author(s):  
SILKE HAVERKAMP ◽  
FRANCOISE HAESELEER ◽  
ANITA HENDRICKSON
Keyword(s):  
Bipolar Cell ◽  
Horizontal Cell ◽  
Outer Part ◽  
Amacrine Cells ◽  
Cell Types ◽  
Macaque Monkey ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Double Labeling ◽  
Wide Range

As more human retinas affected with genetic or immune-based diseases become available for morphological analysis, it is important to identify immunocytochemical markers for specific subtypes of retinal neurons. In this study, we have focused on bipolar cell markers in central retina. We have done single and double labeling using several antisera previously utilized in macaque monkey or human retinal studies and two new antisera (1) to correlate combinations of antisera labeling with morphological types of bipolar cells in human retina, and (2) to compare human labeling patterns with those in monkey retina. Human bipolar cells showed a wide range of labeling patterns with at least ten different bipolar cell types identified from their anatomy and marker content. Many bipolar cell bodies in the outer part of the inner nuclear layer contained combinations of protein kinase C alpha (PKCα), Islet-1, glycine, and Goα. Bipolar cells labeled with these markers had axons terminating in the inner half of the inner plexiform layer (IPL), consistent with ON bipolar cells. Bipolar cell bodies adjacent to the amacrine cells and with axons in the outer half of the IPL contained combinations of recoverin, glutamate transporter-1, and PKCβ, or CD15 and calbindin. Bipolar cells labeled with these markers were presumed OFF bipolar cells. Calcium-binding protein 5 (CaB5) labeled both putative ON and OFF bipolar cells. Using this cell labeling as a criteria, most cell bodies close to the horizontal cells were ON bipolar cells and almost all bipolar cells adjacent to the amacrine cells were OFF with a band in the middle 2–3 cell bodies thick containing intermixed ON and OFF bipolar cells. Differences were found between human and monkey bipolar cell types labeled by calbindin, CaB5, and CD15. Two new types were identified. One was morphologically similar to the DB3, but labeled for CD15 and CaB5. The other had a calbindin-labeled cell body adjacent to the horizontal cell bodies, but did not contain any accepted ON markers. These results support the use of macaque monkey retina as a model for human, but caution against the assumption that all labeling patterns are identical in the two primates.

Glycine receptors in the rod pathway of the macaque monkey retina

1996 ◽  
Vol 13 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Ulrike Grünert ◽  
Heinz Wässle
Keyword(s):  
Calcium Binding ◽  
Ganglion Cells ◽  
Glycine Receptor ◽  
Outer Part ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Macaque Monkey ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Chemical Synapse

AbstractThe distribution of glycinergic synapses in macaque monkey retina was investigated. The monoclonal antibody (mAb2b) against the αl subunit of the glycine receptor produced a punctate immunoreactivity that was localized to synapses. In central retina about 70% of the αl subunit-containing synapses were located in strata 1 and 2 of the inner plexiform layer, about 30% were located in strata 3 and 4, and immunoreactivity was absent in stratum 5. Electron microscopy showed that the majority of the synapses in strata 1 and 2 were on cone bipolar axons. The presynaptic profile always belonged to an amacrine cell. Presynaptic and postsynaptic profiles were further characterized using double-label immunofluorescence with cell-type specific antibodies against calcium-binding proteins. An antiserum against calretinin was used to label A<doubt/>II amacrine cells and an antiserum against recoverin was used to label flat midget bipolar cells. In the outer part of the IPL, 75% of the αl-immunoreactive puncta were colocalized with calretinin-immunoreactive An processes and 61% of the αl-immunoreactive puncta were colocalized with recoverin-positive midget bipolar axons. These results suggest that the αl subunit of the glycine receptor is present at the chemical synapse made by A<doubt/>II amacrine cells with flat midget bipolar cells, thus providing a pathway for rod signals to reach midget ganglion cells.

Organization of the primate retina: Light microscopy, with an appendix: A second type of midget bipolar cell in the primate retina

1969 ◽  
Vol 255 (799) ◽  
pp. 109-184 ◽  
Keyword(s):  
Ganglion Cell ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Horizontal Cell ◽  
Light And Electron Microscopy ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Inner Plexiform Layer ◽  
Axon Terminals

The structure of the human, but mainly of the rhesus monkey, retina as examined by Golgi-staining techniques is described and interpreted on evidence from both light and electron microscopy. One type of rod bipolar cell and two types of cone bipolar cell are recognized. The rod bipolar is exclusively connected to rods. The midget bipolar is postsynaptic to only one cone but each cone is also presynaptic to a diffuse cone (flat) bipolar. Such flat bipolar cells are in synaptic relationship with about seven cones. No other bipolar cell types have been found. The brush bipolar of Polyak is interpreted as probably a distorted rod bipolar, while Polyak’s centrifugal bipolar is a misinterpretation of the morphology of diffuse amacrine cells. When presumptive centrifugal bipolars were observed they appeared to be a developmental stage of amacrine cells. In the outer plexiform layer two types of horizontal cell have been defined. Each type of horizontal cell has a single axon and two kinds of horizontal cell axon terminals are recognized. In the inner plexiform layer there are two main classes of amacrine cells: the stratified amacrines and the diffuse amacrines. Each class of amacrine has a wide variety of shapes. Polyak’s midget ganglion cell is confirmed and his five other kinds of ganglion cell are classified into diffuse and stratified ganglion cells according to the level at which their dendrites branch within the inner plexiform layer. A fuller summary is given by the diagram and in the legend of figure 98, p. 174. A new type of midget bipolar is described in the Appendix (p. 177).

scholarly journals Identification of retinal neurons in a regressive rodent eye (the naked mole-rat)

2004 ◽  
Vol 21 (2) ◽  
pp. 107-117 ◽  
Author(s):  
STEPHEN L. MILLS ◽  
KENNETH C. CATANIA
Keyword(s):  
Ganglion Cells ◽  
Horizontal Cell ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Heterocephalus Glaber ◽  
Mole Rat ◽  
Naked Mole Rat

The retina consists of many parallel circuits designed to maximize the gathering of important information from the environment. Each of these circuits is comprised of a number of different cell types combined in modules that tile the retina. To a subterranean animal, vision is of relatively less importance. Knowledge of how circuits and their elements are altered in response to the subterranean environment is useful both in understanding processes of regressive evolution and in retinal processing itself. We examined common cell types in the retina of the naked mole-rat,Heterocephalus glaberwith immunocytochemical markers and retrograde staining of ganglion cells from optic nerve injections. The stains used show that the naked mole-rat eye has retained multiple ganglion cell types, 1–2 types of horizontal cell, rod bipolar and multiple types of cone bipolar cells, and several types of common amacrine cells. However, no labeling was found with antibodies to the dopamine-synthesizing enzyme, tyrosine hydroxylase. Although most of the well-characterized mammalian cell types are present in the regressive mole-rat eye, their structural organization is considerably less regular than in more sighted mammals. We found less precision of depth of stratification in the inner plexiform layer and also less precision in their lateral coverage of the retina. The results suggest that image formation is not very important in these animals, but that circuits beyond those required for circadian entrainment remain in place.

scholarly journals Characterization of a novel large-field cone bipolar cell type in the primate retina: Evidence for selective cone connections

2010 ◽  
Vol 28 (1) ◽  
pp. 29-37 ◽  
Author(s):  
HANNAH R. JOO ◽  
BETH B. PETERSON ◽  
TONI J. HAUN ◽  
DENNIS M. DACEY
Keyword(s):  
Giant Cell ◽  
Bipolar Cell ◽  
Visual Information ◽  
Dendritic Tree ◽  
Cell Types ◽  
Giant Cells ◽  
Bipolar Cells ◽  
Large Field ◽  
Inner Plexiform Layer ◽  
Dendritic Field

AbstractParallel processing of visual information begins at the first synapse in the retina between the photoreceptors and bipolar cells. Ten bipolar cell types have been previously described in the primate retina: one rod and nine cone bipolar types. In this paper, we describe an 11th type of bipolar cell identified in Golgi-stained macaque retinal whole mount and vertical section. Axonal stratification depth, in addition to dendritic and axonal morphology, distinguished the “giant” cell from all previously well-recognized bipolar cell types. The giant bipolar cell had a very large and sparsely branched dendritic tree and a relatively large axonal arbor that costratified with the DB4 bipolar cell near the center of the inner plexiform layer. The sparseness of the giant bipolar’s dendritic arbor indicates that, like the blue cone bipolar, it does not contact all the cones in its dendritic field. Giant cells contacting the same cones as midget bipolar cells, which are known to contact single long-wavelength (L) or medium-wavelength (M) cones, demonstrate that the giant cell does not exclusively contact short-wavelength (S) cones and, therefore, is not a variant of the previously described blue cone bipolar. This conclusion is further supported by measurement of the cone contact spacing for the giant bipolar. The giant cell contacts an average of about half the cones in its dendritic field (mean ± s.d. = 52 ± 17.6%; n = 6), with a range of 27–82%. The dendrites from single or neighboring giant cells that converge onto the same cones suggest that the giant cell may selectively target a subset of cones with a highly variable local density, such as the L or M cones.

scholarly journals Heterocellular coupling between amacrine cell and ganglion cells

2018 ◽  
Author(s):  
Robert E. Marc ◽  
Crystal Sigulinsky ◽  
Rebecca L. Pfeiffer ◽  
Daniel Emrich ◽  
James R. Anderson ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Ganglion Cell ◽  
Bipolar Cell ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Tem Analysis

AbstractAll superclasses of retinal neurons display some form of electrical coupling including the key neurons of the inner plexiform layer: bipolar cells (BCs), amacrine or axonal cells (ACs) and ganglion cells (GCs). However, coupling varies extensively by class. For example, mammalian rod bipolar cells form no gap junctions at all, while all cone bipolar cells form class-specific coupling arrays, many of them homocellular in-superclass arrays. Ganglion cells are unique in that classes with coupling predominantly form heterocellular cross-class arrays of ganglion cell::amacrine cell (GC::AC) coupling in the mammalian retina. Ganglion cells are the least frequent superclass in the inner plexiform layer and GC::AC gap junctions are sparsely arrayed amidst massive cohorts of AC::AC, bipolar cell BC::BC, and AC::BC gap junctions. Many of these gap junctions and most ganglion cell gap junctions are suboptical, complicating analysis of specific ganglion cells. High resolution 2 nm TEM analysis of rabbit retinal connectome RC1 allows quantitative GC::AC coupling maps of identified ganglion cells. Ganglion cells classes apparently avoid direct cross-class homocellular coupling altogether even though they have opportunities via direct membrane touches, while transient OFF alpha ganglion cells and transient ON directionally selective (DS) ganglion cells are strongly coupled to distinct amacrine / axonal cell cohorts.A key feature of coupled ganglion cells is intercellular metabolite flux. Most GC::AC coupling involves GABAergic cells (γ+ amacrine cells), which results in significant GABA flux into ganglion cells. Surveying GABA coupling signatures in the ganglion cell layer across species suggests that the majority of vertebrate retinas engage in GC::AC coupling.Multi-hop synaptic queries of the entire RC1 connectome clearly profiles the coupled amacrine and axonal cells. Photic drive polarities and source bipolar cell class selec-tivities are tightly matched across coupled cells. OFF alpha ganglion cells are coupled to OFF γ+ amacrine cells and transient ON DS ganglion cells are coupled to ON γ+ amacrine cells including a large interstitial axonal cell (IAC). Synaptic tabulations show close matches between the classes of bipolar cells sampled by the coupled amacrine and ganglion cells. Further, both ON and OFF coupling ganglion networks show a common theme: synaptic asymmetry whereby the coupled γ+ neurons are also presynaptic to ganglion cell dendrites from different classes of ganglion cells outside the coupled set. In effect, these heterocellular coupling patterns enable an excited ganglion cell to directly inhibit nearby ganglion cells of different classes. Similarly, coupled γ+ amacrine cells engaged in feedback networks can leverage the additional gain of bipolar cell synapses in shaping the signaling of a spectrum of downstream targets based on their own selective coupling with ganglion cells.

Localization of NMDA receptor subunits and mapping NMDA drive within the mammalian retina

2004 ◽  
Vol 21 (4) ◽  
pp. 587-597 ◽  
Author(s):  
MICHAEL KALLONIATIS ◽  
DANIEL SUN ◽  
LISA FOSTER ◽  
SILKE HAVERKAMP ◽  
HEINZ WÄSSLE
Keyword(s):  
Nmda Receptor ◽  
Distribution Pattern ◽  
Splice Variants ◽  
Horizontal Cell ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Metabotropic Receptors ◽  
Ionotropic Receptor

Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.

Morphological and functional identifications of catfish retinal neurons. I. Classical morphology

1975 ◽  
Vol 38 (1) ◽  
pp. 53-71 ◽  
Author(s):  
K. Naka ◽  
N. R. Garraway
Keyword(s):  
Ganglion Cells ◽  
Horizontal Cell ◽  
Dendritic Tree ◽  
Amacrine Cells ◽  
Cell Types ◽  
Bipolar Cells ◽  
Inner Nuclear Layer ◽  
Horizontal Cells ◽  
Specific Cell ◽  
Definition Of

The morphology of the catfish horizontal cells is comparable to that in other fish retinas. The external horizontal cells contact cone receptors and are stellate in shape; the intermediate horizontal cells are even more so and contact rod receptors. The internal horizontal cells constitute the most proximal layer of the inner nuclear layer and may possibly be, in reality, extended processes from the other two horizontal cell types. Bipolar cells resemble those in other teleost retinas: the size and shape of their dendritic tree encompass a continuous spectrum ranging from what is known as the small to the large bipolar cells. The accepted definition of amacrine cells is sufficiently vague to justify our originating a more descriptive and less inferential name for the (axonless) neurons in the inner nuclear layer which radiate processes throughout the inner synaptic layer. These starbust and spaghetti cells vary considerably in the character and extent of their dendritic spread, but correlates exist in other vertebrate retinas. Ganglion cells are found not only in the classical ganglion layer but displaced into the inner nuclear layer as well. Several types can be distinguished on the basis of cell geometry and by the properties of their dendritic tree. Not all of the categorization corresponds with previous descriptions; our findings suggest that some reorganization may be necessary in the accepted classification of cells in the proximal areas of the vertebrate retina. A subtle yet remarkable pattern underlies the entire structure of the catfish retina; there exists a definite gradient of size within a particular class of cells, and of configuration among the subclasses of a specific cell type. It remains to be seen if these morphological spectra bear any functional consequences. The fact that the structure of the catfish retina most closely resembles those of other phylogenetically ancient animals, such as the skate and the dogfish shark, testifies to its primitive organization; morphological and functional mechanisms discernible in this simple system may, therefore, be applicable to the retinas of higher ordered vertebrates.

The interplexiform cell system II. Effects of dopamine on goldfish retinal neurones

1978 ◽  
Vol 201 (1142) ◽  
pp. 27-55 ◽  
Keyword(s):  
Horizontal Cell ◽  
Cell Activity ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell System ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Inner Plexiform Layer ◽  
Specific Effects ◽  
Β Blocker

The effects of atomized solutions of dopamine and certain related com­pounds have been tested on the intracellularly recorded activity of receptor, horizontal, bipolar and amacrine cells in the goldfish retina. Dopamine depolarizes the cone L-type horizontal cells and reduces the amplitude of light-evoked responses. These effects on L-type horizontal cells are completely abolished by the α-adrenergie blocker, phentolamine, but only partially depressed by the β-blocker, propanolol. L-Dopa, noradrenalin, and serotonin do not have effects on L-type horizontal cells when applied at concentrations similar to those that cause maximal dopamine effects. The results suggest that the effects of dopamine on L-type horizontal cells are specific, and we propose that they mimic the effects of interplexiform cell activity. Dopamine has no effects on rod horizontal cells in goldfish and variable effects on C-type horizontal cells. On bipolar cells, dopamine alters the dark membrane potential, enhances the central response to light, and depresses the surround response. Dopamine also decreases the horizontal cell feedback evident in cone responses. Finally, dopamine strongly depolarizes the transient type of amacrine cells, but it has no significant effect on the sustained type of amacrine cells. Assuming that dopamine is the transmitter of interplexiform cells, we suggest that these neurons regulate lateral inhibitory effects mediated by L-type horizontal cells in the outer plexiform layer and transient amacrine cells in the inner plexiform layer. In addition, it appears as if interplexiform cells have specific effects on bipolar cells and are capable of regulating centre-surround antagonism in these cells. The net effect of interplexiform cell activity is to isolate the bipolars from the influence of the surround.

scholarly journals Morphology and function of three VIP-expressing amacrine cell types in the mouse retina

2015 ◽  
Vol 114 (4) ◽  
pp. 2431-2438 ◽  
Author(s):  
Alejandro Akrouh ◽  
Daniel Kerschensteiner
Keyword(s):  
Mammalian Species ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Light Responses ◽  
Wide Range ◽  
Asymmetric Distributions ◽  
And Function

Amacrine cells (ACs) are the most diverse class of neurons in the retina. The variety of signals provided by ACs allows the retina to encode a wide range of visual features. Of the 30–50 AC types in mammalian species, few have been studied in detail. Here, we combine genetic and viral strategies to identify and to characterize morphologically three vasoactive intestinal polypeptide-expressing GABAergic AC types (VIP1-, VIP2-, and VIP3-ACs) in mice. Somata of VIP1- and VIP2-ACs reside in the inner nuclear layer and somata of VIP3-ACs in the ganglion cell layer, and they show asymmetric distributions along the dorsoventral axis of the retina. Neurite arbors of VIP-ACs differ in size (VIP1-ACs ≈ VIP3-ACs > VIP2-ACs) and stratify in distinct sublaminae of the inner plexiform layer. To analyze light responses and underlying synaptic inputs, we target VIP-ACs under 2-photon guidance for patch-clamp recordings. VIP1-ACs depolarize strongly to light increments (ON) over a wide range of stimulus sizes but show size-selective responses to light decrements (OFF), depolarizing to small and hyperpolarizing to large stimuli. The switch in polarity of OFF responses is caused by pre- and postsynaptic surround inhibition. VIP2- and VIP3-ACs both show small depolarizations to ON stimuli and large hyperpolarizations to OFF stimuli but differ in their spatial response profiles. Depolarizations are caused by ON excitation outweighing ON inhibition, whereas hyperpolarizations result from pre- and postsynaptic OFF-ON crossover inhibition. VIP1-, VIP2-, and VIP3-ACs thus differ in response polarity and spatial tuning and contribute to the diversity of inhibitory and neuromodulatory signals in the retina.

Expression of glycine and the glycine transporter Glyt-1 in the developing rat retina

2000 ◽  
Vol 17 (1) ◽  
pp. 1-9 ◽  
Author(s):  
DAVID V. POW ◽  
ANITA E. HENDRICKSON
Keyword(s):  
Ganglion Cells ◽  
Outer Part ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Inner Plexiform Layer ◽  
Rat Retina ◽  
Glycine Transporter ◽  
Developing Rat

Previous studies show that glycine transporter-1 (glyt-1) is a consistent membrane marker of adult retinal neurons that are likely to release glycine at their synaptic terminals (Pow, 1998; Vaney et al., 1998; Pow & Hendrickson, 1999). The current study investigated when glyt-1 immunoreactivity appeared in the postnatal rat retina, and whether all glycine-containing neurons also labelled for glyt-1. Ganglion cells, horizontal cells, and photoreceptors showed transient labelling. Many cells in the ganglion cell layer are immunoreactive for both glycine and glyt-1 at postnatal day (Pd) 1 but both are minimal by Pd5. Transient immunoreactivity for both glyt-1 and glycine was observed in presumptive horizontal cells between Pd5 and Pd10. At Pd1 many cells in the outer part of the retina which resembled immature photoreceptors were heavily labelled for glycine, but did not express glyt-1; these disappeared at older ages. These findings suggest diverse mechanisms and transient roles for glycine in the developing rat retina. In the adult rat retina, a subpopulation of amacrine cells are prominently immunoreactive for both glycine and glyt-1. These cells labelled for glycine at Pd1, but did not express significant levels of glyt-1 until Pd5. Processes from these amacrine cells did not reach the inner half of the inner plexiform layer until Pd10–14. Bipolar cells became glycine-IR between Pd10 and Pd14, but consistently lacked any glyt-1 immunoreactivity. This temporal pattern of labelling strongly indicates that bipolar cells label for glycine when gap junctions become functional between glycine/glyt-1 immunoreactive amacrine cells and cone bipolar cells.

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