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PubMedDate not supplied

Horizontal cell morphology in nocturnal and diurnal primates: a comparison between owl-monkey (Aotus) and capuchin monkey (Cebus).

Horizontal cell morphology was studied in the retina of the nocturnal owl-monkey, Aotus, and compared with that of its diurnal, close relative, the capuchin monkey, Cebus . Cells were initially labeled with DiI and the staining was later photoconverted in a stable precipitated using DAB as chromogen. The sizes of cell bodies, dendritic fields, and axon terminals, number of dendritic clusters, intercluster spacing, and intercone spacing were measured at increasing eccentricities. Two distinct morphological classes of horizontal cells were identified, which resembled those of H1 and H3 cells described in diurnal monkeys. A few examples of a third class, possibly corresponding to the H2 cells of diurnal monkeys, were labeled. Both H1 and H3 cells increased in size and had increasing numbers of dendritic clusters with eccentricity. H3 cells were larger and had a larger number of dendritic clusters than H1 cells. Owl-monkey H1 cells had larger dendritic fields than capuchin monkey H1 cells at all quadrants in the central and midperipheral retinal regions, but the difference disappeared in the far periphery. Owl-monkey and capuchin monkey H1 cells had about the same number of dendritic clusters across eccentricity. As owl-monkey H1 cells were larger than capuchin monkey H1 cells, the equal number of clusters in these two primates was due to the fact that they were more spaced in the owl-monkey cells. H1 intercluster distance closely matched intercone spacing for both the owl-monkey and capuchin monkey retinas. On the other hand, H3 intercluster distance was larger than intercone spacing in the retina of both primates. Owl-monkey H1 axon terminals had 2-3 times more knobs than capuchin monkey H1 axon terminals in spite of having about the same size and, consequently, knob density was 2-3 times higher for owl-monkey than capuchin monkey H1 axon terminals across all eccentricities. The differences observed between owl-monkey and capuchin monkey horizontal cells, regarding the morphology of their dendritic trees and axon terminals, may be related to the differences found in the cone-to-rod ratio in the retina of these two primates. They seem to represent retinal specializations to the nocturnal and diurnal life styles of the owl-monkey and capuchin monkey, respectively.

Animals↗

PubMed2006

Immunocytochemical analysis of GABA-positive and calretinin-positive horizontal cells in the tiger salamander retina.

By using immunocytochemical techniques, we demonstrate that there are two distinct, nonoverlapping populations of horizontal cells (HCs) in the tiger salamander retina: GABA-positive cells account for about 72% and GABA-negative (calretinin-positive) cells account for 28% of the total HC somas. The calretinin-positive HCs have relatively sparse and thick dendrites: soma diameter of 19.72 +/- 0.29 microm, and soma density of 140 +/- 13 cells/mm(2), morphological features very much like the A-type HCs described in the accompanying article. The GABA-positive HCs have thinner dendritic and coarse axon-terminal-like processes of higher density: soma diameter of 18 +/- 0.18 microm, and soma density of 364 +/- 18 cells/mm(2), features that very much resemble the B-type HCs and B-type HC axon terminals in the accompanying article. By using double and triple immunostaining techniques we found that only 18% of the non-GABAergic HC dendritic clusters contact rods, whereas the remaining 82% of the dendritic clusters contact cones. This is consistent with the physiological finding in the accompanying article that the A-type HCs are cone-dominated. On the other hand, 32% of GABAergic HC dendrites contact rod pedicles and 68% contact cone pedicles, consistent with the physiological finding that B-type HCs and B-type HC axon terminals receive mixed rod/cone inputs. Detailed confocal microscope analysis shows that 4% rods, 6% principal double cones/single cones, and 100% accessory double cones contact calretinin-positive HCs, and 79% rods, 100% principal double cones, 14% accessory double cones, and 82% single cones contact GABAergic HCs. These results suggest that GABAergic and non-GABAergic HC input/output synapses differ and they may mediate different functional pathways in the outer retina.

Ambystoma↗

PubMed1992

Immunohistochemical localization of basic fibroblast growth factor in mature and developing retinas of normal and RCS rats.

Basic fibroblast growth factor (bFGF) delays photoreceptor degeneration when injected intraocularly in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy. In the present study, we have determined the localization of endogenous bFGF in retinas of normal and RCS rats during the normal developmental period (postnatal days 0-20) and the period of photoreceptor degeneration in RCS rats (days 20-90). bFGF was localized immunohistochemically by indirect immunoperoxidase using two different polyclonal antibodies and one monoclonal antibody against bFGF. bFGF was present in retinas as early as birth, and remained through adult age. Controls using either PBS, non-immune IgG or antibody preabsorbed with bFGF peptide were devoid of label. In normal rats between the ages of birth and postnatal day (P) 4, bFGF was found in developing ganglion cells, superficial blood vessels, some of the innermost cells in the neuroblastic layer, developing horizontal cells, and retinal pigment epithelial (RPE) cells. Between P0 and P4, the intensity of staining increased significantly in horizontal cells. From P6-P10, some cells in the inner nuclear layer remained positive, but horizontal cell staining became less intense in the central retina. The superficial vessels, ganglion cells and RPE cells also remained positive for bFGF. At P20-25, when the retina was essentially mature, bFGF was found in RPE cells, most cells of the ganglion cell layer, and many cells of the inner nuclear layer, but horizontal cells and blood vessels showed a lower concentration of bFGF than they did at younger ages. At P45 and older, blood vessels no longer showed bFGF immunoreactivity. The staining pattern in RCS rats was indistinguishable from that for normal rats at all ages examined. These results show that bFGF is present in the developing and adult rat retina in some neural cells, in addition to vessels and RPE cells. The transient elevated expression of bFGF immunoreactivity in developing horizontal cells and blood vessels suggests a possible role for this growth factor in retinal development. In addition, if RCS retinas possess any difference in bFGF localization or concentration compared to normal retinas, it must be too small to detect by immunohistochemical means, or at least with the reagents used.

Animals↗

PubMed2005

Depolarizing effect of GABA in horizontal cells of the rabbit retina.

Gamma-amino butyric acid (GABA) has been characterized as an inhibitory neurotransmitter acting through chloride mediated channels in the adult nervous system. Using gramicidin-perforated patch clamp recordings from horizontal cells dissociated from the retinas of adult rabbits, we found that GABA is able to induce cell depolarization. Ionic currents induced by GABA in dissociated horizontal cells showed a reversal potential close to -30 mV. This value is more positive than the resting potential of these cells (ca. -70 mV). Therefore, according to the Nernst equation, the intracellular chloride concentration in horizontal cells was estimated to be of 44 mM. The depolarizing effect of GABA at the dendrites of horizontal cells may serve to shape the center-surround organization of the receptive fields in retinal cells, thereby securing the shape discrimination of visual input.

Animals↗

PubMed2007

Epidermal growth factor receptor in adult retinal neurons of rat, mouse, and human.

During development, the epidermal growth factor receptor (EGFR) regulates proliferation and differentiation of many types of cells, including precursors of neurons and glia. In the adult, EGFR continues to drive the growth and differentiation of epithelial cells but is absent from glia in the CNS. However, the localization and functions of EGFR in adult neurons are not well defined. By using immunohistochemistry and Western blotting, we have identified EGFR and its ligands in adult retinal ganglion cells in the normal rat, mouse, and human retina. EGFR and its ligands were also present in certain other adult retinal neurons, for example, horizontal cells and amacrine cells, and had different distribution patterns among these species. In addition, we found that EGFR was expressed in the rat retinal ganglion cell line RGC-5. One of the EGFR ligands, EGF, caused a cell shape change and increased neurofilament phosphorylation in RGC-5 cells. The expression of EGFR in postmitotic, terminally differentiated adult retinal neurons suggests that EGFR has pleiotropic functions. In addition to the conventional mitogenic role in adult epithelial cells, EGFR must serve a different, nonmitogenic function in adult neurons. Our work localizes EGFR and its ligands in the adult retinas of several species as a step toward investigating the nonmitogenic functions of EGFR in adult neurons.

Aged↗

PubMed2002

Cellular localization of the vesicular inhibitory amino acid transporter in the mouse and human retina.

Horizontal cells are classically thought to mediate lateral inhibition by gamma-aminobutyric acid (GABA)-transporter mediated release. In the mammalian retina, however, GABA uptake and cloned GABA transporter were not detected in horizontal cells. Furthermore, the vesicular inhibitory amino acid transporter (VIAAT or VGAT) that loads GABA and glycine into synaptic vesicles was reported recently to be expressed in horizontal cells. To further assess synaptic transmission in mammalian horizontal cells, we examined the subcellular distribution of VIAAT in mouse and human retina by confocal microscopy with specific cell markers. VIAAT was observed in the mouse outer plexiform layer as punctate structures that localized in calbindin-positive horizontal cells. These structures were in close apposition with synaptophysin-, PSD-95-, dystrophin-, and bassoon-immunopositive photoreceptor terminals, suggesting that VIAAT is localized in horizontal cell tips at photoreceptor terminals. VIAAT-positive puncta were also in apposition to lectin-labeled cone terminals or dendrites of PKCalpha-immunopositive rod bipolar cells, indicating that VIAAT is expressed in horizontal cell tips at both rod and cone terminals. By contrast, only a very few puncta were observed in the human outer plexiform layer, whereas the inner plexiform layer remained labeled as in the mouse retina. When using adult human retinal cells in culture, horizontal cells identified by parvalbumin immunostaining were found to contain VIAAT, either at their terminals or throughout the entire cell similarly as in syntaxin-immunopositive cells. These differences between human retinal tissue and cultured cells were attributed to VIAAT degradation in postmortem retinal tissue. VIAAT localization in mouse and human horizontal cells further support the role of inhibitory transmitters in lateral inhibition at the photoreceptor terminals.

Amino Acid Transport Systems↗

PubMed1998

Nerve growth factor receptor TrkA is expressed by horizontal and amacrine cells during chicken retinal development.

Nerve growth factor is known to stimulate neurite outgrowth and support neuronal survival during embryonic development. We have studied the expression of the nerve growth factor receptor, TrkA, at both mRNA and protein levels during the course of chicken retinal development. Furthermore, we have compared the expression of trkA mRNA with that of the 75-kD low-affinity neurotrophin receptor (p75NTR). RNase protection assay identified peak-levels of trkA mRNA in the late embryonic retina. Using in situ hybridization and immunohistochemistry, we found cells expressing TrkA in both the internal and the external part of the inner nuclear layer, corresponding to amacrine and horizontal cells, respectively. The TrkA-expressing amacrine cell has a unistratified dendritic arborization in the second sublamina of the inner plexiform layer, and may represent the stellate amacrine cell described by Cajal. The horizontal cells, possessing arciform dendrite processes in the outer plexiform layer, showed strong TrkA immunoreactivity in both dendrites and cell bodies. During the course of retinal development, the TrkA-expressing amacrine cells decreased in number, whereas the TrkA-expressing horizontal cells persisted. Because nerve growth factor was expressed where the horizontal cells, but not where the amacrine cells were located, these findings raise the question of whether nerve growth factor could locally support the survival of TrkA-expressing interneurons during retinal development.

Animals↗

PubMed1995

Calbindin immunoreactivity of horizontal cells in the developing rabbit retina.

Horizontal cells are retinal interneurons that establish inhibitory feedback loops within the outer plexiform layer of the primary visual pathway. Most mammalian retinas contain two types of horizontal cells. A-type horizontal cells have neuritic branches that contact cone photoreceptors exclusively, while the B-type horizontal cells have dendritic branches that contact cones, in addition to axons that form synapses with rod photoreceptors. Immunoreactivity for calbindin, a calcium binding protein involved in calcium transport, was used as a marker for horizontal cells during post-natal development of the rabbit retina. On post-natal days 1, 3 and 5, calbindin immunoreactivity is limited to a single population of A-type horizontal cells. They appear as a monolayer of cells with broad tapering processes, establishing the proximal border of the nascent outer plexiform layer and forming a target for ingrowing cone photoreceptor terminals. The size and density of the cell bodies and the length of neuritic processes are essentially unchanged during this period, which corresponds to the time of peak expression of GABAergic markers in horizontal cells. Coincident with a decrease in GABAergic markers and the completion of cone-to-horizontal cell synaptogenesis by day 7, changes within the horizontal cell mosaic are detected morphometrically. A delayed phase of overall cell growth results in a 70% increase in average somal diameter (representing a 3.7-fold increase in spherical volume), a six-fold increase in mean neurite length and a decrease in cell density to one-third of that found in the newborn. We conclude that the process of terminal differentiation of horizontal cells is not complete until some time after the second post-natal week. Furthermore, the expression of GABAergic markers is associated primarily with early maturational events, whereas expression of calbindin is sustained throughout post-natal development, suggesting a prominent role for calcium dependent mechanisms at all development stages.

Animals↗

PubMedDate not supplied

Regularity and packing of the horizontal cell mosaic in different strains of mice.

The present study describes the relationships between mosaic regularity, intercellular spacing, and packing of horizontal cells across a two-fold variation in horizontal cell density in four strains of mice. We have tested the prediction that mosaic patterning is held constant across variation in density following our recent demonstration that intercellular spacing declines as density increases, by further examination of that dataset: Nearest-neighbor and Voronoi-domain analyses were conducted on multiple fields of horizontal cells from each strain, from which their respective regularity indices were calculated. Autocorrelation analysis was performed on each field, from which the density recovery profile was generated, and effective radius and packing factor were calculated. The regularity indexes showed negative correlations with density rather than being held constant, suggesting that the strong negative correlation between intercellular spacing and density exceeded that required to produce a simple scaling of the mosaic. This was confirmed by the negative correlation between packing factor and density. These results demonstrate that the variation in the patterning present in the population of horizontal cells across these strains is a consequence of epigenetic mechanisms controlling intercellular spacing as a function of density.

Animals↗

PubMed1993

Consequences of transient retinal hypoxia on rod input to horizontal cells in the rat retina.

The effects of hypoxia on horizontal cells were studied by intracellular recording in the superfused rat retina. Hypoxic challenge from the photoreceptor surface resulted in horizontal cell depolarization, associated with a reduction of the light-evoked hyperpolarization (S-potential). This depolarization, though not the reduction in S-potential, was reversed by non-NMDA receptor antagonists, but not by NMDA related antagonists. Horizontal cells were also depolarized during hypoxia when calcium-dependent synaptic transmitter release was blocked by Co2+. Diazoxide, an activator of ATP-sensitive K+ channels (K+ATP), had no effect on normal cells but blocked the depolarization and the reduction in S-potential. We conclude that retinal hypoxia results in increased activation of the non-NMDA receptors of horizontal cells, whilst the activation of K+ATP channels may be protective in retinal hypoxia.

Animals↗

PubMed2006

Horizontal cell receptive fields are reduced in connexin57-deficient mice.

Horizontal cells are coupled by gap junctions; the extensive coupling of the horizontal cells is reflected in their large receptive fields, which extend far beyond the dendritic arbor of the individual cell. In the mouse retina, horizontal cells express connexin57 (Cx57). Tracer coupling of horizontal cells is impaired in Cx57-deficient mice, which suggests that the receptive fields of Cx57-deficient horizontal cells might be similarly reduced. To test this hypothesis we measured the receptive fields of horizontal cells from wildtype and Cx57-deficient mice. First, we examined the synaptic connections between horizontal cells and photoreceptors: no major morphological alterations were found. Moreover, horizontal cell spacing and dendritic field size were unaffected by Cx57 deletion. We used intracellular recordings to characterize horizontal cell receptive fields. Length constants were computed for each cell using the cell's responses to concentric light spots of increasing diameter. The length constant was dependent on the intensity of the stimulus: increasing stimulus intensity reduced the length constant. Deletion of Cx57 significantly reduced horizontal cell receptive field size. Dark resting potentials were strongly depolarized and response amplitudes reduced in Cx57-deficient horizontal cells compared to the wildtype, suggesting an altered input resistance. This was confirmed by patch-clamp recordings from dissociated horizontal cells; mean input resistance of Cx57-deficient horizontal cells was 27% lower than that of wildtype cells. These data thus provide the first quantification of mouse horizontal cell receptive field size and confirm the unique role of Cx57 in horizontal cell coupling and physiology.

Animals↗

PubMedDate not supplied

Response of carp (Cyprinus carpio) horizontal cells to heterochromatic flicker photometry.

The objective of the present work was to determine the interaction of cone inputs in the response of horizontal cells using heterochromatic flicker photometry (HFP). Intracellular electrophysiological recordings were made in horizontal cells of isolated retinae of carp maintained in physiological solution, with the receptor side up. Sharp glass microelectrodes filled with 3 M KCl solution with resistances between 100 and 120 M Omega were used. Stimuli comprised six cycles of two 6-Hz sinusoidal light waves in counterphase adjusted for the same number of quanta: a green light (550 nm) from a monochromator with a Xenon lamp and an LED red light (628 nm). The stimulation program consisted of 10 steps with the 550-nm wave at constant amplitude, while the 628-nm wave varied in increments of 10% up to 100%, followed by another 10 steps with the 628-nm wave at constant amplitude while the 550-nm wave varied in increments of 10% up to 100%. We recorded responses from four different horizontal cell classes: H1 (monophasic, broadband, n = 37), H2 (biphasic, red-green color-opponent, n = 13), and H3 (biphasic, blue-yellow color-opponent, n = 2) cone horizontal cells; and RH (monophasic, broadband, n = 3) rod horizontal cells. H1 and RH horizontal cells showed a similar cancellation point at a heterochromatic mixture consistent with mixed inputs from 630- and 550-nm cones. No cancellation point was found for the H2 cell class. Fish H1 cells add cone inputs and signal "luminance" in light levels appropriate for cone stimulation. The same occurs with RH cells, which also signal "luminance," but in light levels appropriate for rod work. For both cell classes there is an HFP cancellation point occurring at a combination of 628-nm and 550-nm lights in opposing phase that leads to the cancellation of the cell's response. No cancellation was found for H2 and H3 cells, which are the chromatically opponent horizontal cells in lower vertebrates.

Animals↗

PubMed2007

Heterogeneity of horizontal cells in the chicken retina.

Despite numerous reports that different markers are expressed by horizontal cells in the avian retina, it remains unknown whether different types of horizontal cells can be defined by differences in their immunocytochemical profiles. The purpose of this study was to rectify this deficiency. We identified horizontal cells by indirect immunofluorescence with antibodies to calretinin, trkA, GABA, Prox1, AP2alpha, Pax6, islet1, and Lim1 + 2. We found two major groups of horizontal cells, those that express trkA and those that express calretinin. The trkA-immunoreactive (-IR) horizontal cells had small, round somata and robust, bulbous dendritic endings, whereas calretinin-IR horizontal cells had large, polygonal cell bodies and fine, diffuse dendritic endings, both contacting the calbindin-IR pedicles of double cones. Weak gamma-aminobutyric acid (GABA) immunoreactivity was observed only in a few of the trkA-IR horizontal cells, whereas the overlap of calretinin and GABA immunoreactivities was 100%. The majority of trkA-IR horizontal cells expressed islet1, and the majority of calretinin-IR horizontal cells expressed Lim1 + 2, AP2alpha, and Pax6. Islet1 immunoreactivity was observed in a small fraction of calretinin-IR/non-trkA-IR cells. In agreement with previous reports, we detected Prox1 immunoreactivity in all types of horizontal cells. These immunolabeling profiles suggest that there are four immunochemically distinct subtypes of horizontal cells in the postnatal chick retina, which may match the four types that have been observed in Golgi-impregnated pigeon and turtle retinas.

Animals↗

PubMed2006

Intracellular calcium is regulated by different pathways in horizontal cells of the mouse retina.

Horizontal cells modulate the output of the photoreceptor to bipolar cell synapse, thereby providing the first level of lateral information processing in the vertebrate retina. Because horizontal cells do not generate sodium-based action potentials, calcium is likely to play an important role for graded potential changes as well as for intracellular events involved in the modulatory role of horizontal cells within the retinal network. Therefore we wanted to determine how the activation of glutamate receptors, voltage-gated calcium channels, and release of calcium from internal stores shape the calcium signal in horizontal cells. All horizontal cells responded to depolarizing voltage steps with sustained inward currents, which activated at around -20 mV, reached a peak amplitude of -79.1 pA at 5 mV, and reversed sign at around 66 mV. The current was insensitive to tetrodotoxin, and it was partially blocked by the L-type channel antagonists verapamil and nifedipine. The N-type channel blocker omega-conotoxin GVIA induced an additional reduction of current amplitudes. Calcium influx through ionotropic glutamate receptors was mediated by both AMPA and kainate but not by N-methyl-D-aspartate receptors. Two agonists at group I metabotropic glutamate receptor, trans-1-amino-1,3-cyclopentanedicarboxylic acid and quisqualate, had no effect. However, intracellular calcium was increased by caffeine, indicating release of calcium from internal stores via ryanodine receptors. These data show that intracellular calcium in horizontal cells is regulated by voltage-dependent L- and N-type calcium channels, ionotropic AMPA and kainate receptors, and release of calcium from internal stores after activation of ryanodine receptors.

Animals↗

PubMed2006

Coupling between A-type horizontal cells is mediated by connexin 50 gap junctions in the rabbit retina.

There are many examples of neuronal coupling via gap junctions in the retina. Of these, perhaps the best known is the extensive coupling between horizontal cells. In the rabbit retina, there are two types of horizontal cells, A-type and B-type, both of which are independently coupled. Connexin 50 (Cx50) cDNA, encoding a 440 aa protein, was successfully isolated from rabbit retina RNA. Cx50 was also obtained from isolated A-type horizontal cells (A-type HCs) by single-cell RT-PCR. A-type HCs were visualized by intracellular dye injection or with an antibody against calbindin. Confocal analysis revealed all Cx50 labeling occurred on the A-type HC matrix, typically at dendritic intersections. The Cx50 plaques varied in size, from punctate signals in which fine dendrites cofasciculated, to giant plaques, >50 microm(2), in which large dendrites crossed. The numerous Cx50 plaques between A-type HCs may adequately account for the remarkable coupling observed in this network. We could not detect Cx50 staining on the tips of horizontal cell dendrites within the cone pedicle invagination. This distribution does not support a role for Cx50 in hemichannel-mediated feedback. In addition, the absence of Cx50 in B-type HCs suggests the presence of a different connexin for this cell type. In summary, these results suggest that gap junctions in the A-type horizontal cell matrix are composed from Cx50. Multiple neuronal connexins are expressed in the mammalian retina and different cell types express specific connexins.

Animals↗

PubMed2006

Effects of mercury intoxication on the response of horizontal cells of the retina of thraira fish (Hoplias malabaricus).

Methyl mercury (MeHg) is highly neurotoxic, affecting visual function in addition to other central nervous system functions. The effect of mercury intoxication on the amplitude of horizontal cell responses to light was studied in the retina of the fish Hoplias malabaricus. Intracellular responses were recorded from horizontal cells of fish previously intoxicated with MeHg by intraperitoneal injection (IP group) or by trophic exposure (T group). Only one retina per fish was used. The doses of MeHg chloride administered to the IP group were 0.01, 0.05, 0.1, 1.0, 2.0, and 6.0 mg/kg. The amplitudes of the horizontal cell responses were lower than control in individuals exposed to 0.01 (N = 4 retinas), 0.05 (N = 2 retinas) and 0.1 mg/kg (N = 1 retina), whereas no responses were recorded in the 1.0, 2.0, and 6.0 mg/kg groups. T group individuals were fed young specimens of Astyanax sp previously injected with MeHg corresponding to 0.75 (N = 1 retina), 0.075 (N = 8 retinas) or 0.0075 (N = 4 retinas) mg/kg fish body weight. After 14 doses, one every 5 days, the amplitude of the horizontal cell response was higher than control in individuals exposed to 0.075 and 0.0075 mg/kg, and lower in individuals exposed to 0.75 mg/kg. We conclude that intoxication with MeHg affects the electrophysiological response of the horizontal cells in the retina, either reducing or increasing its amplitude compared to control, and that these effects are related to the dose and/or to the mode of administration.

Animals↗

PubMed2006

An ionotropic GABA receptor with novel pharmacology at bullfrog cone photoreceptor terminals.

Characteristics of ionotropic gamma-aminobutyric acid (GABA) receptors at bullfrog cone terminals were studied by patch clamp techniques in isolated cell and retinal slice preparations. GABA-induced inward currents from isolated cones reversed in polarity at a potential, very close to the chloride equilibrium potential, and they were completely suppressed by picrotoxin. Unexpectedly, the GABA current was dose-dependently potentiated by the well-known GABA(A) receptor antagonist bicuculline (BIC), but was suppressed by gabazine, another GABA(A) antagonist, and imidazole-4-acetic acid (I4AA), a GABA(C) receptor antagonist. Similarly, currents induced by both GABA(A) agonist muscimol and GABA(C) agonist cis-4-aminocrotonic acid (CACA) were also potentiated by BIC. Furthermore, currents induced from cones by GABA and kainate-caused depolarization of horizontal cells in retinal slice preparations were both potentiated by BIC. All these results suggest that the ionotropic GABA receptor at the bullfrog cone terminal exhibits novel pharmacology, distinct from both traditional GABA(A) and GABA(C) receptors.

Animals↗

PubMed2004

Timing and topography of cell genesis in the rat retina.

To understand the mechanisms of cell fate determination in the vertebrate retina, the time course of the generation of the major cell types needs to be established. This will help define and interpret patterns of gene expression, waves of differentiation, timing and extent of competence, and many of the other developmental processes involved in fate acquisition. A thorough retinal cell "birthdating" study has not been performed for the laboratory rat, even though it is the species of choice for many contemporary developmental studies of the vertebrate retina. We investigated the timing and spatial pattern of cell genesis using 3H-thymidine (3H-TdR). A single injection of 3H-TdR was administered to pregnant rats or rat pups between embryonic day (E) 8 and postnatal day (P) 13. The offspring of prenatally injected rats were delivered and all animals survived to maturity. Labeled cells were visualized by autoradiography of retinal sections. Rat retinal cell genesis commenced around E10, 50% of cells were born by approximately P1, and retinogenesis was complete near P12. The first postmitotic cells were found in the retinal ganglion cell layer and were 9-15 microm in diameter. This range includes small to medium diameter retinal ganglion cells and large displaced amacrine cells. The sequence of cell genesis was established by determining the age at which 5, 50, and 95% of the total population of cells of each phenotype became postmitotic. With few exceptions, the cell types reached these developmental landmarks in the following order: retinal ganglion cells, horizontal cells, cones, amacrine cells, rods, bipolar cells, and Müller glia. For each type, the first cells generated were located in the central retina and the last cells in the peripheral retina. Within the sequence of cell genesis, two or three phases could be detected based on differences in timing, kinetics, and topographic gradients of cell production. Our results show that retinal cells in the rat are generated in a sequence similar to that of the primate retina, in which retinogenesis spans more than 100 days. To the extent that sequences reflect underlying mechanisms of cell fate determination, they appear to be conserved.

Animals↗