RESUMO
The Old World macaque monkey and New World common marmoset provide fundamental models for human visual processing, yet the human ancestral lineage diverged from these monkey lineages over 25 Mya. We therefore asked whether fine-scale synaptic wiring in the nervous system is preserved across these three primate families, despite long periods of independent evolution. We applied connectomic electron microscopy to the specialized foveal retina where circuits for highest acuity and color vision reside. Synaptic motifs arising from the cone photoreceptor type sensitive to short (S) wavelengths and associated with "blue-yellow" (S-ON and S-OFF) color-coding circuitry were reconstructed. We found that distinctive circuitry arises from S cones for each of the three species. The S cones contacted neighboring L and M (long- and middle-wavelength sensitive) cones in humans, but such contacts were rare or absent in macaques and marmosets. We discovered a major S-OFF pathway in the human retina and established its absence in marmosets. Further, the S-ON and S-OFF chromatic pathways make excitatory-type synaptic contacts with L and M cone types in humans, but not in macaques or marmosets. Our results predict that early-stage chromatic signals are distinct in the human retina and imply that solving the human connectome at the nanoscale level of synaptic wiring will be critical for fully understanding the neural basis of human color vision.
Assuntos
Visão de Cores , Conectoma , Animais , Humanos , Callithrix , Percepção de Cores/fisiologia , Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Macaca , CercopithecidaeRESUMO
The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single-cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Müller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post-mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell-derived cone photoreceptors and an adult Müller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.
Assuntos
Degeneração Neural/genética , RNA Longo não Codificante/genética , Retina/química , Análise de Célula Única/métodos , Transcriptoma , Autopsia , Análise por Conglomerados , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Humanos , Especificidade de Órgãos , Células Fotorreceptoras Retinianas Bastonetes/química , Análise de Sequência de RNA , Aprendizado de Máquina não SupervisionadoRESUMO
Two main subcortical pathways serving conscious visual perception are the midget-parvocellular (P), and the parasol-magnocellular (M) pathways. It is generally accepted that the P pathway serves red-green color vision, but the relative contribution of P and M pathways to spatial vision is a long-standing and unresolved issue. Here, we mapped the spatial sampling properties of P and M pathways across the human retina. Data were obtained from immunolabeled vertical sections of six postmortem male and female human donor retinas and imaged using high-resolution microscopy. Cone photoreceptors, OFF-midget bipolar cells (P pathway), OFF-diffuse bipolar (DB) types DB3a and DB3b (M pathway), and ganglion cells were counted along the temporal horizontal meridian, taking foveal spatial distortions (postreceptoral displacements) into account. We found that the density of OFF-midget bipolar and OFF-midget ganglion cells can support one-to-one connections to 1.05-mm (3.6°) eccentricity. One-to-one connections of cones to OFF-midget bipolar cells are present to at least 10-mm (35°) eccentricity. The OFF-midget ganglion cell array acuity is well-matched to photopic spatial acuity measures throughout the central 35°, but the OFF-parasol array acuity is well below photopic spatial acuity, supporting the view that the P pathway underlies high-acuity spatial vision. Outside the fovea, array acuity of both OFF-midget and OFF-DB cells exceeds psychophysical measures of photopic spatial acuity. We conclude that parasol and midget pathway bipolar cells deliver high-acuity spatial signals to the inner plexiform layer, but outside the fovea, this spatial resolution is lost at the level of ganglion cells.SIGNIFICANCE STATEMENT We make accurate maps of the spatial density and distribution of neurons in the human retina to aid in understanding human spatial vision, interpretation of diagnostic tests, and the implementation of therapies for retinal diseases. Here, we map neurons involved with the midget-parvocellular (P pathway) and parasol-magnocellular (M pathway) through human retina. We find that P-type bipolar cells outnumber M-type bipolar cells at all eccentricities. We show that cone photoreceptors and P-type pathway bipolar cells are tightly connected throughout the retina, but that spatial resolution is lost at the level of the ganglion cells. Overall, the results support the view that the P pathway is specialized to serve both high acuity vision and red-green color vision.
Assuntos
Retina/citologia , Retina/fisiologia , Vias Visuais/citologia , Vias Visuais/fisiologia , Adulto , Feminino , Fóvea Central/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Células Bipolares da Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/fisiologia , Acuidade VisualRESUMO
Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium-binding protein calbindin. These calbindin-rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation. Further, the K layers and IPul are both involved in visual processing and have similar connections with retina and superior colliculus. Here, we confirmed the continuity between calbindin-rich cells in LGN K layers and the central lateral division of IPul (IPulCL) in marmoset monkeys. By employing a high-throughput neuronal tracing method, we found that both the K layers and IPulCL form comparable patterns of connections with striate and extrastriate cortices; these connections are largely different to those of the parvocellular and magnocellular laminae of LGN. Retrograde tracer-labelled cells and anterograde tracer-labelled axon terminals merged seamlessly from IPulCL into LGN K layers. These results support continuity between LGN K layers and IPulCL, providing an anatomical basis for functional congruity of this region of the dorsal thalamic matrix and calling into question the traditional segregation between LGN and the inferior pulvinar nucleus.
Assuntos
Corpos Geniculados/patologia , Pulvinar/patologia , Córtex Visual/patologia , Vias Visuais/fisiologia , Animais , Corpos Geniculados/fisiologia , Neurônios/fisiologia , Terminações Pré-Sinápticas/patologia , Terminações Pré-Sinápticas/fisiologia , Pulvinar/fisiologia , Tálamo/patologia , Tálamo/fisiologia , Córtex Visual/fisiologiaRESUMO
In primate retina, the calcium-binding protein calbindin is expressed by a variety of neurons including cones, bipolar cells, and amacrine cells but it is not known which type(s) of cell express calbindin in the ganglion cell layer. The present study aimed to identify calbindin-positive cell type(s) in the amacrine and ganglion cell layer of human and marmoset retina using immunohistochemical markers for ganglion cells (RBPMS and melanopsin) and cholinergic amacrine (ChAT) cells. Intracellular injections following immunolabeling was used to reveal the morphology of calbindin-positive cells. In human retina, calbindin-labeled cells in the ganglion cell layer were identified as inner and outer stratifying melanopsin-expressing ganglion cells, and ON ChAT (starburst amacrine) cells. In marmoset, calbindin immunoreactivity in the ganglion cell layer was absent from ganglion cells but present in ON ChAT cells. In the inner nuclear layer of human retina, calbindin was found in melanopsin-expressing displaced ganglion cells and in at least two populations of amacrine cells including about a quarter of the OFF ChAT cells. In marmoset, a very low proportion of OFF ChAT cells was calbindin-positive. These results suggest that in both species there may be two types of OFF ChAT cells. Consistent with previous studies, the ratio of ON to OFF ChAT cells was about 70 to 30 in human and 30 to 70 in marmoset. Our results show that there are species-related differences between different primates with respect to the expression of calbindin.
Assuntos
Células Amácrinas/metabolismo , Calbindinas/metabolismo , Neurônios Colinérgicos/metabolismo , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Adulto , Animais , Callithrix/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Injeções Intraoculares , Masculino , Especificidade da EspécieRESUMO
Visual signals are segregated into parallel pathways at the first synapse in the retina between cones and bipolar cells. Within the OFF pathways of mammals, the selective expression of AMPA or kainate-type glutamate receptors in the dendrites of different OFF-bipolar cell types is thought to contribute to formation of distinct temporal channels. AMPA receptors, with rapid recovery from desensitization, are proposed to transmit high temporal frequency signals, whereas kainate receptors (KARs) are presumed to encode lower temporal frequencies. Here we studied the glutamate receptors expressed by OFF-bipolar cells in slice preparations of macaque monkey retina, where the low (midget/parvocellular) and high-frequency (parasol/magnocellular) temporal channels are well characterized. We found that all OFF-bipolar types receive input primarily through KARs and that KAR antagonists block light-evoked input to both OFF-midget and OFF-parasol ganglion cells. KAR subunits were differentially expressed in OFF-bipolar types; the diffuse bipolar (DB) cells, DB2 and DB3b, expressed GluK1 and showed transient responses to glutamate and the KAR agonist, ATPA. In contrast, flat midget bipolar, DB1, and DB3a cells lacked GluK1 and showed relatively sustained responses. Finally, we found that the KAR accessory protein, Neto1, is expressed at the base of cone pedicles but is not colocalized with the GluK1 subunit. In summary, the results indicate that transient signaling in the OFF pathway of macaques is not dependent on AMPA receptors and that heterogeneity of KARs and accessory proteins may contribute to the formation of parallel temporal channels.
Assuntos
Receptores de Ácido Caínico/fisiologia , Retina/fisiologia , Sinapses/fisiologia , Vias Visuais/fisiologia , Animais , Feminino , Macaca fascicularis/fisiologia , Macaca mulatta/fisiologia , Masculino , Técnicas de Cultura de Órgãos , Retina/citologia , Fatores de Tempo , Vias Visuais/citologiaRESUMO
Three well characterized pathways in primate vision (midget-parvocellular, parasol-magnocellular, bistratified-koniocellular) have been traced from the first synapse in the retina, through the visual thalamus (lateral geniculate nucleus, LGN), to the visual cortex. Here we identify a pathway from the first synapse in the retina to koniocellular layer K1 in marmoset monkeys (Callithrix jacchus). Particle-mediated gene transfer of an expression plasmid for the postsynaptic density 95-green fluorescent protein (PSD95-GFP) was used to label excitatory synapses on retinal ganglion cells and combined with immunofluorescence to identify the presynaptic bipolar cells. We found that axon terminals of one type of diffuse bipolar cell (DB6) provide dominant synaptic input to the dendrites of narrow thorny ganglion cells. Retrograde tracer injections into the LGN and photofilling of retinal ganglion cells showed that narrow thorny cells were preferentially labeled when koniocellular layer K1 was targeted. Layer K1 contains cells with high sensitivity for rapid movement, and layer K1 sends projections to association visual areas as well as to primary visual cortex. We hypothesize that the DB6-narrow thorny-koniocellular pathway contributes to residual visual functions ("blindsight") that survive injury to primary visual cortex in adult or early life.
Assuntos
Callithrix/anatomia & histologia , Corpos Geniculados/citologia , Retina/citologia , Células Ganglionares da Retina/citologia , Córtex Visual/citologia , Vias Visuais/citologia , Células Amácrinas/citologia , Células Amácrinas/ultraestrutura , Animais , Axônios , Forma Celular , Dendritos , Feminino , Microscopia Eletrônica , Marcadores do Trato Nervoso , Células Bipolares da Retina/citologia , Células Bipolares da Retina/ultraestrutura , Células Ganglionares da Retina/ultraestrutura , SinapsesRESUMO
Color information is encoded by two parallel pathways in the mammalian retina. One pathway compares signals from long- and middle-wavelength sensitive cones and generates red-green opponency. The other compares signals from short- and middle-/long-wavelength sensitive cones and generates blue-green (yellow) opponency. Whereas both pathways operate in trichromatic primates (including humans), the fundamental, phylogenetically ancient color mechanism shared among most mammals is blue-green opponency. In this review, we summarize the current understanding of how signals from short-wavelength sensitive cones are processed in the primate and nonprimate mammalian retina, with a focus on the inner plexiform layer where bipolar, amacrine, and ganglion cell processes interact to facilitate the generation of blue-green opponency.
Assuntos
Visão de Cores/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Neurônios Retinianos/fisiologia , Vias Visuais/fisiologia , Células Amácrinas/fisiologia , Animais , Opsinas dos Cones/metabolismo , Humanos , Mamíferos , Primatas , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologiaRESUMO
Purpose: A lesion to primary visual cortex (V1) in primates can produce retrograde transneuronal degeneration in the dorsal lateral geniculate nucleus (LGN) and retina. We investigated the effect of age at time of lesion on LGN volume and retinal ganglion cell (RGC) density in marmoset monkeys. Methods: Retinas and LGNs were obtained about 2 years after a unilateral left-sided V1 lesion as infants (n = 7) or young adult (n = 1). Antibodies against RBPMS were used to label all RGCs, and antibodies against CaMKII or GABAA receptors were used to label nonmidget RGCs. Cell densities were compared in the left and right hemiretina of each eye. The LGNs were stained with the nuclear marker NeuN or for Nissl substance. Results: In three animals lesioned within the first 2 postnatal weeks, the proportion of RGCs lost within 5 mm of the fovea was â¼twofold higher than after lesions at 4 or 6 weeks. There was negligible loss in the animal lesioned at 2 years of age. A positive correlation between RGC loss and LGN volume reduction was evident. No loss of CaMKII-positive or GABAA receptor-positive RGCs was apparent within 2 mm of the fovea in any of the retinas investigated. Conclusions: Susceptibility of marmoset RGCs to transneuronal degeneration is high at birth and declines over the first 6 postnatal weeks. High survival rates of CaMKII and GABAA receptor-positive RGCs implies that widefield and parasol cells are less affected by neonatal cortical lesions than are midget-pathway cells.
Assuntos
Callithrix , Células Ganglionares da Retina , Humanos , Animais , Recém-Nascido , Células Ganglionares da Retina/patologia , Receptores de GABA-A , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Córtex Visual Primário , Vias Visuais/patologia , Retina , Proteínas de TransporteRESUMO
The roles of the midget and parasol pathways as the anatomical foundation for high-acuity vision at the fovea are well established. There is also evidence for the presence of other (non-midget, non-parasol) ganglion cell types in the foveal retina, but it is not established whether these cells receive input from cone photoreceptors in the central few degrees of the visual field, i.e. the region most important for conscious visual perception. To address this question, we targeted injections of retrograde tracer to the koniocellular layers in the posterior aspect of the lateral geniculate nucleus, where the central visual field is represented, in marmoset monkeys (Callithrix jacchus). Labeled ganglion cells were photofilled to reveal their dendritic morphology. Potential inputs to foveal koniocellular cells from diffuse bipolar cells were investigated in vertical sections through the fovea of marmoset and macaque (Macaca fascicularis) monkey retinas using immunohistochemistry. Forty koniocellular-projecting ganglion cells were analysed. We used an established model of marmoset foveal topography to show that all these koniocellular-projecting cells receive cone inputs from the central-most 6°, with about half the cells receiving input from below 2° eccentricity, in the rod-free central bouquet of cones at the foveola. In addition, all diffuse bipolar types investigated were present in the fovea at stratification depths similar to those of their counterparts in the peripheral retina. We conclude that the diverse visual representations established for koniocellular pathways in the peripheral retina are also a feature of the fovea, suggesting that koniocellular pathways contribute to foveal vision.
Assuntos
Fóvea Central/citologia , Células Bipolares da Retina/citologia , Células Ganglionares da Retina/citologia , Animais , Callithrix , Dendritos/ultraestrutura , Macaca fascicularis , Células Fotorreceptoras Retinianas Cones/citologia , Células Ganglionares da Retina/classificaçãoRESUMO
Parasol-magnocellular pathway ganglion cells form an important output stream of the primate retina and make a major contribution to visual motion detection. They are known to comprise ON and OFF type response polarities but the relative numbers of ON and OFF parasol cells, and the overall contribution of parasol cells to high-acuity foveal vision are not well understood. Here we use antibodies against carbonic anhydrase 8 (CA8) and intracellular injections of the liphilic dye DiI to show that CA8 selectively labels OFF parasol cells in macaque retina. By combined labeling with CA8 antibodies and a previously-described marker for parasol cells (GABAA receptor antibodies), we show that ON and OFF parasol cells each comprise â¼ 6% of all ganglion cells in central retina (each peak density â¼ 3000 cells/mm2 at 5 deg.), and each population comprises â¼ 10% of all ganglion cells in peripheral temporal retina. Thus, the spatial density of parasol cells in central retina is greater than reported by previous anatomical studies, and the central-peripheral gradient in parasol cell density is shallower than previously reported. The data nevertheless predict decline in spatial acuity with visual field eccentricity for both midget-parvocellular pathway and parasol-magnocellular pathway mediated visual functions. The spatial resolving power of the OFF parasol array (peak â¼ 7 cpd) falls short of macaque behavioral grating acuity by at least a factor of three throughout the retina.
Assuntos
Macaca , Células Ganglionares da Retina , Animais , Células Ganglionares da Retina/fisiologia , Haplorrinos , Retina/fisiologia , Campos VisuaisRESUMO
Retinal ganglion cells receive excitatory synapses from bipolar cells and inhibitory synapses from amacrine cells. Previous studies in primate suggest that the strength of inhibitory amacrine input is greater to cells in peripheral retina than to foveal (central) cells. A comprehensive study of a large number of ganglion cells at different eccentricities, however, is still lacking. Here, we compared the amacrine and bipolar input to midget and parasol ganglion cells in central and peripheral retina of marmosets (Callithrix jacchus). Ganglion cells were labeled by retrograde filling from the lateral geniculate nucleus or by intracellular injection. Presumed amacrine input was identified with antibodies against gephyrin; presumed bipolar input was identified with antibodies against the GluR4 subunit of the AMPA receptor. In vertical sections, about 40% of gephyrin immunoreactive (IR) puncta were colocalized with GABAA receptor subunits, whereas immunoreactivity for gephyrin and GluR4 was found at distinct sets of puncta. The density of gephyrin IR puncta associated with ganglion cell dendrites was comparable for midget and parasol cells at all eccentricities studied (up to 2 mm or about 16 degrees of visual angle for midget cells and up to 10 mm or >80 degrees of visual angle for parasol cells). In central retina, the densities of gephyrin IR and GluR4 IR puncta associated with the dendrites of midget and parasol cells are comparable, but the average density of GluR4 IR puncta decreased slightly in peripheral parasol cells. These anatomical results indicate that the ratio of amacrine to bipolar input does not account for the distinct functional properties of parasol and midget cells or for functional differences between cells of the same type in central and peripheral retina.
Assuntos
Células Amácrinas/fisiologia , Callithrix/fisiologia , Retina/fisiologia , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Células Amácrinas/ultraestrutura , Animais , Western Blotting , Proteínas de Transporte/metabolismo , Dendritos/fisiologia , Dendritos/ultraestrutura , Feminino , Imunofluorescência , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Iontoforese , Masculino , Proteínas de Membrana/metabolismo , Microscopia Eletrônica , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de GABA-A/metabolismo , Receptores de GABA-A/fisiologia , Retina/citologia , Células Bipolares da Retina/ultraestrutura , Células Ganglionares da Retina/ultraestrutura , Sinapses/fisiologiaRESUMO
Immunoreactivity for calcium-/calmodulin-dependent protein kinase II (CaMKII) in the primate dorsal lateral geniculate nucleus (dLGN) has been attributed to geniculocortical relay neurons and has also been suggested to arise from terminals of retinal ganglion cells. Here, we combined immunostaining with single-cell injections to investigate the expression of CaMKII in retinal ganglion cells of three primate species: macaque (Macaca fascicularis, M. nemestrina), human, and marmoset (Callithrix jacchus). We found that in all species, about 2%-10% of the total ganglion cell population expressed CaMKII. In all species, CaMKII was expressed by multiple types of wide-field ganglion cell including large sparse, giant sparse (melanopsin-expressing), broad thorny, and narrow thorny cells. Three other ganglion cells types, namely, inner and outer stratifying maze cells in macaque and tufted cells in marmoset were also found. Double labeling experiments showed that CaMKII-expressing cells included inner and outer stratifying melanopsin cells. Nearly all CaMKII-expressing ganglion cell types identified here are known to project to the koniocellular layers of the dLGN as well as to the superior colliculus. The best characterized koniocellular projecting cell type-the small bistratified (blue ON/yellow OFF) cell-was, however, not CaMKII-positive in any species. Our results indicate that the pattern of CaMKII expression in retinal ganglion cells is largely conserved across different species of primate suggesting a common functional role. But the results also show that CaMKII is not a marker for all koniocellular projecting retinal ganglion cells.
Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Células Ganglionares da Retina , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Callithrix , Corpos Geniculados , Humanos , Macaca fascicularis/metabolismo , Retina/metabolismo , Células Ganglionares da Retina/fisiologiaRESUMO
Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against the transcription factor special AT-rich binding protein 1 (Satb1, a protein which is expressed by on-off direction-selective ganglion cells in mouse retina) to study Satb1 expression in the retina of marmosets (Callithrix jacchus), macaques (Macaca fascicularis), and humans. In all species, Satb1 was exclusively expressed in retinal ganglion cells. The Satb1 cells made up â¼2% of the ganglion cell population in the central retina of all species, rising to a maximum â¼7% in peripheral marmoset retina. Intracellular injections in marmoset and macaque retinas revealed that most Satb1 expressing ganglion cells are widefield ganglion cells. In marmoset, Satb1 cells have a densely branching dendritic tree and include broad and narrow thorny, recursive bistratified, and parasol cells, all of which show some costratification with the outer or inner cholinergic amacrine cells. The recursive bistratified cells showed the strongest costratification but did not show extensive cofasciculation as reported for on-off direction-selective ganglion cells in rabbit and rodent retinas. In macaque, Satb1 was not expressed in recursive bistratified cells, but in large sparsely branching cells. Our findings further support the idea that the expression of transcription factors in retinal ganglion cells is not conserved across Old World (human and macaque) and New World (marmoset) primates and provides a further step to link a molecular marker with specific cell types.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Células Ganglionares da Retina/metabolismo , Animais , Callithrix , Humanos , Macaca fascicularis , Especificidade da EspécieRESUMO
Two morphological types of melanopsin-expressing ganglion cells have been described in primate retina. Both types show intrinsic light responses as well as rod- and cone-driven ON-type responses. Outer stratifying cells have their dendrites close to the inner nuclear layer (OFF sublamina); inner stratifying cells have their dendrites close to the ganglion cell layer (ON sublamina). Both inner and outer stratifying cells receive synaptic input via ribbon synapses, but the bipolar cell types providing this input have not been identified. Here, we addressed the question whether the diffuse (ON) cone bipolar type DB6 and/or rod bipolar cells contact melanopsin-expressing ganglion cells. Melanopsin containing ganglion cells in marmoset (Callithrix jacchus) and macaque (Macaca fascicularis) retinas were identified immunohistochemically; DB6 cells were labeled with antibodies against the carbohydrate epitope CD15, rod bipolar cells were labeled with antibodies against protein kinase C, and putative synapses between the two cells types were identified with antibodies against piccolo. For one inner cell, nearly all of the DB6 axon terminals that overlap with its dendrites in the two-dimensional space show areas of close contact. In vertical sections, the large majority of the areas of close contact also contain a synaptic punctum, suggesting that DB6 cells contact inner melanopsin cells. The output from DB6 cells accounts for about 30% of synapses onto inner melanopsin cells. Synaptic contacts between rod bipolar axons and inner dendrites were not observed. In the OFF sublamina, about 10% of the DB6 axons are closely associated with dendrites of outer cells, and in about a third of these areas, axonal en passant synapses are detected. This result suggests that DB6 cells may also provide input to outer melanopsin cells.
Assuntos
Retina/fisiologia , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Opsinas de Bastonetes/fisiologia , Sequência de Aminoácidos , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Callithrix , Imuno-Histoquímica , Macaca fascicularis , Masculino , Dados de Sequência Molecular , Proteína Quinase C/metabolismo , Sinapses/fisiologia , Sinapses/ultraestruturaRESUMO
The eye sends information about the visual world to the brain on over 20 parallel signal pathways, each specialized to signal features such as spectral reflection (color), edges, and motion of objects in the environment. Each pathway is formed by the axons of a separate type of retinal output neuron (retinal ganglion cell). In this review, we summarize what is known about the excitatory retinal inputs, brain targets, and gene expression patterns of ganglion cells in humans and nonhuman primates. We describe how most ganglion cell types receive their input from only one or two of the 11 types of cone bipolar cell and project selectively to only one or two target regions in the brain. We also highlight how genetic methods are providing tools to characterize ganglion cells and establish cross-species homologies.
Assuntos
Retina , Células Ganglionares da Retina , Animais , Axônios , Primatas/fisiologia , Retina/fisiologia , Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologiaRESUMO
In primates, the retinal ganglion cells contributing to high acuity spatial vision (midget cells and parasol cells), and blue-yellow color vision (small bistratified cells) are well understood. Many other ganglion cell types with large dendritic fields (named wide-field ganglion cells) have been identified, but their spatial density and distribution are largely unknown. Here we took advantage of the recently established molecular diversity of ganglion cells to study wide-field ganglion cell populations in three primate species. We used antibodies against the transcription factor Special AT-rich binding protein 2 (Satb2) to explore its expression in macaque (Macaca fascicularis, M. nemestrina), human and marmoset (Callithrix jacchus) retinas. In all three species, Satb2 cells make up a low proportion (1.5-4%) of the ganglion cell population, with a slight increase from central to peripheral retina. Intracellular dye injections revealed that in macaque and human retinas, the large majority (over 80%) of Satb2 cells are inner and outer stratifying large sparse cells. By contrast, in marmoset retina the majority (over 60%) of Satb2 expressing cells were broad thorny cells, with smaller proportions of recursive bistratified (putative direction-selective), large bistratified, and outer stratifying narrow thorny cells. Our findings imply that Satb2 expression has undergone rapid species specific adaptations during primate evolution, because expression is not conserved across Old World (macaque, human) and New World (marmoset) suborders.
Assuntos
Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/metabolismo , Fatores de Transcrição/análise , Fatores de Transcrição/biossíntese , Animais , Callithrix , Feminino , Humanos , Macaca , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/análise , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Especificidade da EspécieRESUMO
We determined the retinal ganglion cell types projecting to the medial subdivision of inferior pulvinar (PIm) and the superior colliculus (SC) in the common marmoset monkey, Callithrix jacchus. Adult marmosets received a bidirectional tracer cocktail into the PIm (conjugated to Alexa fluor 488), and the SC (conjugated to Alexa fluor 594) using an MRI-guided approach. One SC injection included the pretectum. The large majority of retrogradely labelled cells were obtained from SC injections, with only a small proportion obtained after PIm injections. Retrogradely labelled cells were injected intracellularly in vitro using lipophilic dyes (DiI, DiO). The SC and PIm both received input from a variety of ganglion cell types. Input to the PIm was dominated by broad thorny (41%), narrow thorny (24%) and large bistratified (25%) ganglion cells. Input to the SC was dominated by parasol (37%), broad thorny (24%) and narrow thorny (17%) cells. Midget ganglion cells (which make up the large majority of primate retinal ganglion cells) and small bistratified (blue-ON/yellow OFF) cells were never observed to project to SC or PIm. Small numbers of other wide-field ganglion cell types were also encountered. Giant sparse (presumed melanopsin-expressing) cells were only seen following the tracer injection which included the pretectum. We note that despite the location of pulvinar complex in dorsal thalamus, and its increased size and functional importance in primate evolution, the retinal projections to pulvinar have more in common with SC projections than they do with projections to the dorsal lateral geniculate nucleus.
Assuntos
Pulvinar , Células Ganglionares da Retina , Colículos Superiores , Animais , Callithrix , Corpos Geniculados , Retina , Vias VisuaisRESUMO
Purpose: The purpose of this study was to measure the composition of the inner nuclear layer (INL) in the central and peripheral human retina as foundation data for interpreting INL function and dysfunction. Methods: Six postmortem human donor retinas (male and female, aged 31-56 years) were sectioned along the temporal horizontal meridian. Sections were processed with immunofluorescent markers and imaged using high-resolution, multichannel fluorescence microscopy. The density of horizontal, bipolar, amacrine, and Müller cells was quantified between 1 and 12 mm eccentricity with appropriate adjustments for postreceptoral spatial displacements near the fovea. Results: Cone bipolar cells dominate the INL a with density near 50,000 cells/mm2 at 1 mm eccentricity and integrated total â¼10 million cells up to 10 mm eccentricity. Outside central retina the spatial density of all cell populations falls but the neuronal makeup of the INL remains relatively constant: a decrease in the proportion of cone bipolar cells (from 52% at 1 mm to 37% at 10 mm) is balanced by an increasing proportion of rod bipolar cells (from 9% to 15%). The proportion of Müller cells near the fovea (17%) is lower than in the peripheral retina (27%). Conclusions: Despite large changes in the absolute density of INL cell populations across the retina, their proportions remain relatively constant. These data may have relevance for interpreting diagnostic signals such as the electroretinogram and optical coherence tomogram.
Assuntos
Fóvea Central/citologia , Células Bipolares da Retina/citologia , Adulto , Contagem de Células , Feminino , Humanos , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
This review summarizes our current knowledge of primate including human retina focusing on bipolar, amacrine and ganglion cells and their connectivity. We have two main motivations in writing. Firstly, recent progress in non-invasive imaging methods to study retinal diseases mean that better understanding of the primate retina is becoming an important goal both for basic and for clinical sciences. Secondly, genetically modified mice are increasingly used as animal models for human retinal diseases. Thus, it is important to understand to which extent the retinas of primates and rodents are comparable. We first compare cell populations in primate and rodent retinas, with emphasis on how the fovea (despite its small size) dominates the neural landscape of primate retina. We next summarise what is known, and what is not known, about the postreceptoral neurone populations in primate retina. The inventories of bipolar and ganglion cells in primates are now nearing completion, comprising ~12 types of bipolar cell and at least 17 types of ganglion cell. Primate ganglion cells show clear differences in dendritic field size across the retina, and their morphology differs clearly from that of mouse retinal ganglion cells. Compared to bipolar and ganglion cells, amacrine cells show even higher morphological diversity: they could comprise over 40 types. Many amacrine types appear conserved between primates and mice, but functions of only a few types are understood in any primate or non-primate retina. Amacrine cells appear as the final frontier for retinal research in monkeys and mice alike.