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Purkynĕ's description of pressure phosphenes and modern neurophysiological studies on the generation of phosphenes by eyeball deformation.

(a) When a subject indents one of his eyeballs in total darkness, he immediately perceives light extending slowly across the whole visual field of the indented eye. The appearance and the time course of these pressure or deformation phosphenes are described. (b) With simultaneous binocular indentation of the eyeballs a flickering patterned phosphene is observed. (c) A short history of the research on pressure phosphenes and its consequences for the theories of vision is presented. (d) Purkynĕ's observations of monocular deformation phosphenes are described. He repeatedly noted patterned light structures, which most observers only perceive with simultaneous binocular eyeball deformation. It is suggested that Purkynĕ's deviating observations were caused by amblyopia of one eye. (e) The neurophysiological basis of the monocular pressure phosphenes was investigated by means of microelectrode recordings from single optic tract fibers. The activity of single retinal ganglion cells (on-center, off-center neurons, latency class I [Y-neurons] or latency class II [X-neurons]), was recorded in anaesthetized cats. Eyeball deformation in total darkness led to an activation of the on-center ganglion cells, while the off-center ganglion cells were inhibited. The latency and strength of this activation or inhibition varied considerably between different neurons, but were fairly constant in the same neuron when the eyeball indentation was repeated after a pause of 1-3 min. The latency and strength of neuronal activation or inhibition seemed to be dependent mainly upon the neuron location relative to the point of eyeball indentation. Some on-center neurons also exhibited a short activation at "deformation off". (f) The antagonistic response type of on-center and off-center ganglion cells was also observed when the eyeball was deformed as a hydrostatic open system and the intraocular pressure was kept at 25 mm Hg basic pressure. (g) Dark adaptation up to 45 min affected the deformation responses of retinal neurons only to a small degree, if at all. This corresponds to the observation that deformation phosphenes in a human observer changed little during the course of dark adaptation. (h) We assume that the activation of on-center and inhibition of off-center ganglion cells by eyeball deformation are caused by retinal stretching, which also leads to horizontal cell stretch. Stretching the horizontal cell membrane probably generates an increase in membrane sodium conductivity and a depolarization of the membrane potential. This depolarization of the horizontal cell membrane potential is transmitted either directly or indirectly (via receptor synapses) from the horizontal to the bipolar cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The number, morphology, and distribution of retinal ganglion cells and optic axons in the Australian lungfish Neoceratodus forsteri (Krefft 1870).

Australian lungfish Neoceratodus forsteri may be the closest living relative to the first tetrapods and yet little is known about their retinal ganglion cells. This study reveals that lungfish possess a heterogeneous population of ganglion cells distributed in a horizontal streak across the retinal meridian, which is formed early in development and maintained through to adult stages. The number and complement of both ganglion cells and a population of putative amacrine cells within the ganglion cell layer are examined using retrograde labelling from the optic nerve and transmission electron-microscopic analysis of axons within the optic nerve. At least four types of retinal ganglion cells are present and lie predominantly within a thin ganglion cell layer, although two subpopulations are identified, one within the inner plexiform and the other within the inner nuclear layer. A subpopulation of retinal ganglion cells comprising up to 7% of the total population are significantly larger (>400 microm2) and are characterized as giant or alpha-like cells. Up to 44% of cells within the retinal ganglion cell layer represent a population of presumed amacrine cells. The optic nerve is heavily fasciculated and the proportion of myelinated axons increases with body length from 17% in subadults to 74% in adults. Spatial resolving power, based on ganglion cell spacing, is low (1.6-1.9 cycles deg(-1), n = 2) and does not significantly increase with growth. This represents the first detailed study of retinal ganglion cells in sarcopterygian fish, and reveals that, despite variation amongst animal groups, trends in ganglion cell density distribution and characteristics of cell types were defined early in vertebrate evolution.

Amacrine Cells↗

Spatial-chromatic interactions in C-type horizontal cells of the turtle (Mauremys caspica) retina.

Horizontal cells are second-order retinal neurons that play a key role in spatial information processing. In some cold-blooded vertebrates such as turtles, a subtype of these cells, the chromaticity horizontal cells exhibit color-opponent responses and therefore are considered to be important also for color information processing. To reveal spatial and color interactions, the receptive-field properties of Red/Green and Yellow/Blue chromaticity horizontal cells in the retina of the turtle Mauremys caspica were studied by intracellular recordings from the everted eyecup preparation. We found that the polarity of the photoresponses depended not only upon the wavelength and intensity of the stimulus, but also upon its spatial configuration. Thus, a hyperpolarizing photoresponse that was elicited by full-field stimulation with bright light of wavelength close to the "neutral" one was reversed in polarity to a pure depolarizing one when a small spot or a thin annular pattern were used for stimulation. This finding could not be explained either by different balances between depolarizing and hyperpolarizing inputs to different cells or by stray light that effectively reduced the light intensity in the center of the small spot. Rather, it was found that the depolarizing and hyperpolarizing components were characterized by different receptive-field size and that these differences could account for the dependency of response polarity upon the spatial pattern of the stimulus. These findings indicate that color information processing in turtle C-type horizontal cells is a complex process that depends upon the wavelength and intensity of the light stimulus as well as upon its spatial properties.

Animals↗

Structural basis of orientation sensitivity of cat retinal ganglion cells.

We investigated the structural basis of the physiological orientation sensitivity of retinal ganglion cells (Levick and Thibos, '82). The dendritic fields of 840 retinal ganglion cells labeled by injections of horseradish peroxidase into the dorsal lateral geniculate nucleus (LGNd) or optic tracts of normal cats. Siamese cats, and cat deprived of patterned visual experience from birth by monocular lid-suture (MD) were studied. Mathematical techniques designed to analyze direction were used to find the dendritic field orientation of each cell. Statistical techniques designed for angular data were used to determine the relationship between dendritic field orientation and angular position on the retina (polar angle). Our results indicate that 88% of retinal ganglion cells have oriented dendritic fields and that dendritic field orientation is related systematically to retinal position. In all regions of retina more that 0.5 mm from the area centralis the dendritic fields of retinal ganglion cells are oriented radially, i.e., like the spokes of a wheel having the area centralis at its hub. This relationship was present in all animals and cell types studied and was strongest for cells located close to the horizontal meridian (visual streak) of the retina. Retinal ganglion cells appear to be sensitive to stimulus orientation because they have oriented dendritic fields.

Animals↗

Dlx1, Dlx2, Pax6, Brn3b, and Chx10 homeobox gene expression defines the retinal ganglion and inner nuclear layers of the developing and adult mouse retina.

Distal-less homeobox genes are expressed in the developing forebrain. We assessed Dlx gene expression in the developing and adult mouse retina. Dlx1 and Dlx2 are detected in retinal neuroprogenitors by embryonic day (E) 12.5 (Eisenstat et al. [1999] J. Comp. Neurol. 217-237). At E13.5, the expression of four homeodomain proteins, DLX2, BRN3b, PAX6, and CHX10, define distinct yet overlapping domains in the retinal neuroepithelium. By postnatal day (P) 0, DLX2 is expressed in the neuroblastic layer and the ganglion cell layer (GCL) consisting of ganglion and displaced amacrine cells. DLX1 expression resembles DLX2 to P0 but decreases postnatally. In the adult, DLX2 is localized to ganglion, amacrine, and horizontal cells as determined by coexpression with retinal cell-specific markers. There is coincident expression of DLX2 with gamma-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD)65, and GAD67 in the inner nuclear layer (INL) and GCL. In the adult, DLX2 is coexpressed with BRN3b in ganglion cells; PAX6 in amacrine, horizontal, and ganglion cells; and Chx10 in some bipolar cells. We predict that a combinatorial code of these homeobox genes and others specify retinal cell fate. Our results support a possible role for Dlx1 and Dlx2 in inner retinal development and in the terminal differentiation and/or maintenance of INL interneurons and ganglion cells in the adult. The correlation of DLX2 with GABA expression in the mouse retina closely mirrors the relationship of DLX2 to GABAergic neuronal differentiation in the embryonic forebrain, including neocortex, olfactory bulb and hippocampus, signifying a conservation of function of Dlx genes in the developing central nervous system.

Amacrine Cells↗

Retinal constraints on orientation specificity in cat visual cortex.

Most retinal ganglion cells (Levick and Thibos, 1982) and cortical cells (Leventhal, 1983; Leventhal et al., 1984) subserving peripheral vision respond best to stimuli that are oriented radially, i.e., like the spokes of a wheel with the area centralis at the hub. We have extended this work by comparing directly the distributions of orientations represented in topographically corresponding regions of retina and visual cortex. Both central and peripheral regions were studied. The relations between the orientations of neighboring ganglion cells and the manner in which the overrepresentation of radial orientations is accommodated in the functional architecture of visual cortex were also studied. Our results are based on an analysis of the orientations of the dendritic fields of 1296 ganglion cells throughout the retina and the preferred orientations of 1389 cells located in retinotopically corresponding regions of cortical areas 17, 18, and 19 in the cat. We find that horizontal and vertical orientations are overrepresented in regions of both retina and visual cortex subserving the central 5 degrees of vision. The distributions of the orientations of retinal ganglion cells and cortical cells subserving the horizontal, vertical, and diagonal meridians outside the area centralis differ significantly. The distribution of the preferred orientations of the S (simple) cells in areas 17, 18 and 19 subserving a given part of the retina corresponds to the distribution of the dendritic field orientations of the ganglion cells in that part of retina. The distribution of the preferred orientations of C (complex) cells with narrow receptive fields in area 17 but not C cells with wide receptive fields in areas 17, 18, or 19 subserving a given part of the retina matches the distribution of the orientations of the ganglion cells in that part of retina. The orientations of all of the alpha-cells in 5-9 mm2 patches of retina along the horizontal, vertical, and oblique meridians were determined. A comparison of the orientations of neighboring cells indicates that other than a mutual tendency to be oriented radially, ganglion cells with similar orientations are not clustered in the retina. Reconstructions of electrode penetrations into regions of visual cortex representing peripheral retina indicate that columns subserving radial orientations are wider than those subserving nonradial orientations. Our results provide evidence that the distribution of the preferred orientations of simple cells in visual cortex subserving any region of the visual field matches the distribution of the orientations of the ganglion cells subserving the same region of the visual field.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Retinal topography in reef teleosts. II. Some species with prominent horizontal streaks and high-density areae.

The retinal ganglion cell layer of five species of reef teleosts was studied from Nissl-stained whole-mounts and the distribution of neural elements determined quantitatively. Iso-density contour maps of neurons in the ganglion cell layer revealed a temporal area centralis (ranging from 3.5 to 8.3 x 10(4) cells/mm2) which often extended into a horizontal streak (ranging from 1.4 to 5.0 x 10(4) cells/mm2) across the retinal meridian. Species possessing a marked horizontal streak were found to inhabit open water and perceive their environment with an uninterrupted view of sand-water horizon. The behavioural significance of these horizontal areas of acute vision is also discussed.

Animals↗

A new type of wide-field horizontal cell, presumably linked to blue cones, in rabbit retina.

Horizontal cells of vertebrate retina play an important role in the formation of visual receptive field surrounds of bipolar cells, and hence in the centre-surround receptive field organization of retinal ganglion cells. In some retinas, horizontal cells also play a major functional role in the first stage of colour-coding of visual stimuli. We have identified a new type of horizontal cell, called 'type C', in rabbit retina, which unlike type A and type B horizontal cells, contacts only a small fraction of cone photoreceptors, possibly blue cones. The multiple, sparsely branched axons of type C cells are well-positioned to contact bipolar dendrites in a feedforward manner. In summary, we propose (1) that the presence in rabbit retina of 3 types of cone horizontal cell, A, B, and C, may represent a more common pattern in mammalian retinae, shared with many non-mammalian retinas which contain colour-coded neurons, (2) that type C cells connect principally to blue cones, and (3) that type C cells are more common in retinas, such as those of squirrels, and to a lesser extent rabbits, in which blue cones play a major role in the colour coding of visual signals.

Animals↗

Quantitative morphological study of the outer nuclear layer in the turtle retina.

Types and densities of retinal cells with somata located in the outer nuclear layer of the turtle retina were studied with combined light and electron microscopic observations of serial sections. One third of the somata in the outer nuclear layer were found to be those of displaced bipolar cells, while the rest were of those of photoreceptors. Somata were 8-10 micrometers in horizontal diameter for both types of retinal cells.

Animals↗

Neural computations in the tiger salamander and mudpuppy outer retinae and an analysis of GABA action from horizontal cells.

A neural network architecture based on the neural anatomy and function of retinal neurons in tiger salamander and mudpuppy retinae is proposed to study basic aspects of early visual information processing. The model predictions for the main response characteristics of retinal neurons are found to be in agreement with neurophysiological data, including the antagonistic role of horizontal cells in the outer plexiform layer. The examination of possible gamma-aminobutyric acid (GABA) action from horizontal cells suggests that GABA(A) alone, GABA(B) alone, or their weighted combination can generate the response characteristics observed in bipolar cells.

Ambystoma↗

Melanopsin: An opsin in melanophores, brain, and eye.

We have identified an opsin, melanopsin, in photosensitive dermal melanophores of Xenopus laevis. Its deduced amino acid sequence shares greatest homology with cephalopod opsins. The predicted secondary structure of melanopsin indicates the presence of a long cytoplasmic tail with multiple putative phosphorylation sites, suggesting that this opsin's function may be finely regulated. Melanopsin mRNA is expressed in hypothalamic sites thought to contain deep brain photoreceptors and in the iris, a structure known to be directly photosensitive in amphibians. Melanopsin message is also localized in retinal cells residing in the outermost lamina of the inner nuclear layer where horizontal cells are typically found. Its expression in retinal and nonretinal tissues suggests a role in vision and nonvisual photoreceptive tasks, such as photic control of skin pigmentation, pupillary aperture, and circadian and photoperiodic physiology.

Amino Acid Sequence↗

GABA-mediated component in the feedback response of turtle retinal cones.

The negative feedback from horizontal cells to cone photoreceptors contributes to the formation of the receptive-field surround in cone photoreceptors. Recently, studies on the modulation of voltage-gated Ca(2+) currents in cone photoreceptors have led to great progress in our understanding of the mechanism of horizontal-cone feedback. Another highly probable hypothesis is that GABA mediates this feedback. This hypothesis is supported by the facts that cone photoreceptors respond to GABA and that horizontal cells release GABA. However, GABA-mediated synaptic inputs from horizontal cells to cone photoreceptors have not been demonstrated. In the present study, we examined whether cone photoreceptors receive GABAergic inputs from horizontal cells using a slice patch technique in the turtle retina. When 1 mM of GABA was applied to the cone photoreceptors, GABA-induced currents were activated. GABA-induced currents reversed their polarity at the equilibrium potential of Cl-. The application of 30 microM of SR95531, an antagonist of GABAA receptors, alone did not produce any change in the holding currents. When 200 microM of pentobarbital was introduced to potentiate the GABAergic inputs to the cone photoreceptors, however, the inhibitory action of SR95531 on GABAergic inputs became detectable. The amplitude of the GABAergic inputs, potentiated by pentobarbital, increased when the horizontal cells were depolarized by the application of 20 microM of kainate, while the amplitude decreased when the horizontal cells were hyperpolarized by the application of 10 microM of CNQX. When the cone photoreceptors were voltage clamped at a potential at which the voltage-gated Ca(2+) current was inactive, horizontal-cone feedback was not observed. However, the horizontal-cone feedback became detectable when the GABAergic inputs to the cone photoreceptors were potentiated by pentobarbital. We concluded that the contribution of GABAergic inputs from horizontal cells to cone pedicles in the formation of the receptive-field surround in cone photoreceptors is very limited but that the modulation of voltage-gated Ca(2+) currents in cone photoreceptors is a physiologically relevant mechanism for horizontal-cone feedback.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Retinal input to the nucleus of the optic tract of the cat assessed by antidromic activation of ganglion cells.

We have studied the physiological properties of ganglion cells in the retina of the cat. The experiments were designed to identify those ganglion cells which project to direction-selective cells in the nucleus of the optic tract (NOT), by demonstrating their antidromic activation at low threshold from an electrode in the NOT. These ganglion cells presumably provide the retinal drive to the optokinetic reflex. Altogether, 11 such ganglion cells were identified in a population of 578 cells studied. All 11 were W-cells, with slow-conducting axons. Five of the 11 had on-centre direction-selective receptive fields; the other 6 had a variety of receptive field patterns. Thus, on centre-selective cells form a much higher proportion of the retinal input to direction-selective cells in the NOT than of the overall ganglion cell population. However, their receptive field properties were too varied fully to account for the selectivity of NOT cells for horizontal stimulus movement. In summary the retinal input to the NOT appears to be formed principally or entirely by W-class ganglion cells, including many which are direction selective. It still seems necessary, however, to postulate, some non-retinal mechanism to account for all the receptive field properties of direction-selective NOT cells.

Afferent Pathways↗

Lens opacity and photoreceptor degeneration in the zebrafish lens opaque mutant.

The zebrafish lens opaque (lop) mutant was identified in a chemical mutagenesis screen. The lop mutant, which develops normally through 4 days postfertilization (dpf), exhibits several signs of lens and retinal degeneration at 7 dpf. Histology revealed disrupted lens fibers and increased numbers of nucleated cells within the mutant lens and anterior chamber. The mutant lens also exhibited aberrant epithelial cell morphologies and lacked a definitive transition zone, which suggests that secondary fiber differentiation was interrupted. In addition, the mutant exhibits severely reduced photoreceptors and a reduction in the number of horizontal cells at 7 dpf. Other retinal cell classes appeared unaffected in the mutant. Transmission electron microscopy and opsin immunohistochemistry showed that the different photoreceptor types were generated at the retinal margin, but the rods and cones failed to mature and disappeared. The mutant lens and retina also displayed increased cell proliferation based on proliferating cell nuclear antigen immunolabeling, suggesting that the lens opacity was due to unregulated cell proliferation and undifferentiated cell accumulation within the mutant lens. The lop mutant phenotype supports recent studies showing the lens has a role in regulating teleost retinal development.

Animals↗

Modulation of cone-to-horizontal-cell signal transmission in the turtle retina by magnesium ions.

The modulation by magnesium ions of cone-to-horizontal-cell signal transmission was studied in the turtle superfused everted eye-cup preparation using solutions which contained various concentrations of divalent cations and/or chelating agents (EDTA and EGTA). Removal of magnesium ions from 'normal' solutions had no apparent effect on the horizontal cells provided that 'normal' levels of calcium ions were maintained. Solutions which actively removed calcium but contained 'normal' levels of magnesium hyperpolarized horizontal cells, reduced the amplitude of their photoresponses but also changed the character of these photoresponses; dim stimuli evoked purely depolarizing responses while bright flashes elicited triphasic responses. Active removal of both calcium and magnesium from the superfusate and from retinal stores with chelators depolarized the horizontal cell and eliminated light-evoked responses. These solutions also depolarized the cones but augmented their light-evoked responses. We conclude that magnesium ions can modulate the membrane potential of horizontal cells, but this role can be revealed only in the absence of calcium ions. Further, the depolarizing responses seen in low calcium, 'normal' magnesium superfusion indicate that the ionic mechanisms underlying the horizontal cell photoresponse are more complex than has been previously described.

Animals↗

The uptake of ( - 3 H) aminobutyric acid in the goldfish retina.

After goldfish retinas had been incubated for 1 hr with [gamma-(3)H]aminobutyric acid, we found by autoradiography that the label was localized to a few restricted types of retinal cells. In particular, external and internal horizontal cells from light-stimulated retinas were more heavily labeled than corresponding cells from retinas kept in darkness. Some other cells and tissues in the retina also incorporated the labeled acid. Light stimulation, however, did not cause a pronounced change in the amount of label associated with these cells. Among these were some heavily labeled cells on the vitreal side of the inner nuclear layer, and scattered grains associated with the ganglion cell and optic nerve layers. Electrophoresis of retinal extracts after incubation with the labeled acid also showed that light-stimulated retinas contained about 40-100% more radioactivity than retinas kept in darkness, and that 90% of this activity remained as [gamma-(3)H]aminobutyric acid. The role of the acid in the retina is not known; it is not clear if horizontal cells normally synthesize or store it. The stimulation-dependent accumulation of the labeled acid into horizontal cells suggests that it plays a functional role in these cells.

Aminobutyrates↗

Localization of dopamine D1-receptor to A-type horizontal cells in the rabbit retina by single cell RT-PCR.

Dopamine is an important neurotransmitter regulating light-dark adaptation in the retina. The effect of dopamine is widespread and dependent on the localization of its receptors. We performed single cell RT-PCR on A-type horizontal cells visually selected from dissociated rabbit retinal neurons. Dopamine D1-receptor mRNA was positively identified. Subsequent sequencing of the fragment showed 82% homology with rat D1 receptor and 87% homology with human D1 receptor. This study supported previous observations that dopamine regulated A-type horizontal cell coupling via D1 receptors at the level of transcription.

Adaptation, Ocular↗

Synaptic connections between neurons in living slices of the larval tiger salamander retina.

Synaptic connections between retinal cells were studied by recording simultaneously from pre- and postsynaptic cells in the retinal slice preparation. The time course and waveform of the pre- and postsynaptic light responses were monitored, and the postsynaptic voltage responses to presynaptic current injection were measured. Results obtained provide direct evidence showing that the rod-HBC and rod-HC synapses are sign-preserving, and the rod-DBC, HC-HBC and amacrine-DBC synapses are sign-inverting. Moreover, the synaptic delays between rods and bipolar cells are shorter than that between rods and horizontal cells. The methodology of making retinal slices and the subsequent recording and stimulation procedures are described. The advantages of the retinal slice preparation and its potential in retinal research are discussed.

Ambystoma↗