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[The eye and nutrition].

PURPOSE: To examine the effect of vitamins and trace elements on ocular tissue. MATERIALS AND METHODS: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B12, C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyser, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens. RESULTS: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus. Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B12 deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B12 was found to be related to the circadian rhythm in the retina. Deficiencies of Zn, Cu, Mn, and vitamins A, B12, and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers. In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer. Zn seemed to be necessary for corneal epithelial cell wound healing. DISCUSSION: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance. CONCLUSION: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B12, C, and E are necessary for maintenance of cellular structure and metabolism.

Animals↗

[A 50-year-old man with metamorphopsia and optic nerve swelling].

We report a 50-year-old male having metamorphopsia associated with retinal edema. He was well until one month prior to the present admission when he developed occipital headache and backache. Three weeks later, he noted a sudden onset of twisting of visual images. On admission, he was in no acute distress with well preserved general conditions. Only neurological abnormalities were bilateral papilledema, retinal edema and horizontal nystagmus with a rotatory component. Routine blood chemistries were unremarkable. The CSF contained 28 cells/cmm with 60% consisting of large atypical cells. Cranial CT scans revealed no mass, however, the magnified orbital CT showed bilateral swelling of the optic nerve. He was treated with ventriculoperitoneal shunt and Ommaya tube placement through which methotrexate, cytarabine and prednisolone were administered. He was also treated with systemic cisplatin, mitomycin-C and 5-fluorouracil. With these therapy, his headache, metamorphopsia and papilledema improved. He was discharged for out-patient follow-up, however, he had to admitted again because of progressive difficulty of gait and loss of appetite. On admission, he complained of severe backache, and his gait disturbance appeared to be in part due to his backache. A slight weakness was noted in all four limbs with loss of deep reflexes. Mentally he was alert and cranial nerves appeared intact without papilledema. But nuchal rigidity was noted. Cranial CT scan revealed attenuation of all the cortical sulci and marked diffuse low density changes in the cerebral white matter, and his chest film revealed a ring-shape shadow in his left lung field. He deteriorated progressively with terminal gastrointestinal hemorrhage. He expired three weeks after his second admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Effects of synaptic drugs on turtle optokinetic nystagmus and the spike responses of the basal optic nucleus.

Behavioral and electrophysiological measures were used to elucidate the retinal modulation of oculomotor control in the turtle. Eye movements were recorded following intravitreal applications of 2-amino-4-phosphonobutyrate (APB) and the GABA antagonists picrotoxin and bicuculline. Visual responses of single basal optic nucleus (BON) neurons of the accessory optic system were studied in parallel experiments. The effectiveness of APB, a glutamate analog thought to act selectively on the retinal ON pathway, was assessed independently by recording electroretinograms or ganglion cell activity. Injections of APB into the turtle's eye reduced or blocked the injected eye's ability to drive horizontal optokinetic nystagmus, as also observed in rabbit and cat (Knapp et al., 1988; Yucel et al., 1989). Single-unit recordings from the BON during APB superfusion (50-200 microM APB) of the contralateral retina demonstrated that these cells, which are direction-sensitive and respond to the offset of light flashes, have their responses to moving stimuli blocked by APB. During the APB effect, GABA antagonists were applied to the same eye. Although moderate doses of APB were sufficient to block optokinetic or BON light responses, the addition of GABA blockers still elicited a spontaneous temporal-to-nasal nystagmus (Ariel, 1989) or visually responsive yet direction-insensitive responses from BON cells (Schuerger et al., 1990). These results are discussed in terms of the retinal output to pathways involved in oculomotor control of optokinetic nystagmus.

Aminobutyrates↗

Different types of synapses with different spectral types of cones underlie color opponency in a bipolar cell of the turtle retina.

Electrophysiologically, color-opponent retinal bipolar cells respond with opposite polarities to stimulation with different wavelengths of light. The origin of these different polarities in the same bipolar cell has always been a mystery. Here we show that an intracellularly recorded and HRP-injected, red-ON, blue/green-OFF bipolar cell of the turtle retina made invaginating (ribbon associated) synapses exclusively with L-cones. Non-invaginating synapses resembling wide-cleft basal junctions were made exclusively with M-cones. Input from S-cones was not seen. From these results we suggest sign-inverting transmission from L-cones at invaginating synapses via metabotropic glutamate receptors, and sign-conserving transmission from M-cones at wide-cleft basal junctions via ionotropic receptors. To explain the pronounced blue sensitivity of the bipolar cell, computer simulations were performed using a sign-conserving input from a yellow/blue chromaticity-type (H3) horizontal cell. The response properties of the red-ON, blue/green-OFF bipolar cell could be quantitatively reproduced by this means. The simulation also explained the asymmetry in L- and M-cone inputs to the bipolar cell as found in the ultrastructural analysis and assigned a putative role to H3 horizontal cells in color processing in the turtle retina.

Animals↗

Repetitive light stimulation inducing glycine receptor plasticity in the retinal neurons.

Neurotransmitter receptor plasticity is a mechanism that can regulate the temporal and intensity encoding of a synapse. While this has been extensively studied as a mechanism of learning, less is known about such processes in sensory systems. This study examines modulation of glycine receptor function at the first synapse in the retina. It was found that horizontal cells, which are postsynaptic to photoreceptors, have glycine receptor currents that are enhanced when internal calcium is elevated. This can be achieved by glutamatergic synaptic input or by activation of voltage-gated calcium channels. When the retina was maintained in a dark-adapted state, the calcium levels in horizontal cells were relatively low. After a series of brief light stimuli, the internal calcium concentration in horizontal cells was elevated, and the glycine currents were faster and greater in amplitude. The increase of internal calcium levels was caused by increased transmitter release from photoreceptors. Thus glycine receptor function is state dependent and can be rapidly altered by synaptic input from photoreceptors. Light stimulation drives glycine receptor plasticity in the retinal neural network.

Animals↗

GABA release induced by aspartate-mediated activation of NMDA receptors is modulated by dopamine in a selective subpopulation of amacrine cells.

Glutamate and GABA are the major excitatory and inhibitory neurotransmitters in the CNS, including the retina. In the chick retina, GABA is located in horizontal and amacrine cells and in some cells in the ganglion cell layer. It has been shown that glutamate and its agonists, NMDA, kainate, and aspartate, promote the release of GABA from isolated retina and from cultured retinal cells. Dopamine, the major catecholamine in the retina, inhibits the induction of GABA release by NMDA. Two to seven-day-old intact chicken retinas were stimulated with different glutamatergic agonists and the GABA remaining in the tissue was detected by immunohistochemical procedures. The exposure of retinas to 100 microM NMDA for 30 minutes resulted in 50% reduction in the number of GABA-immunoreactive amacrine cells. Aspartate (100 microM) treatment also resulted in 60% decrease in the number of GABA-immunoreactive amacrine cells. The number of GABA-immunoreactive horizontal cells was not affected by either NMDA or aspartate. In addition, dopamine reversed by 50% the reduction of the number of GABA-immunoreactive amacrine cells exposed to NMDA or aspartate. Kainate stimulation promoted a 50% reduction in the number of both GABA-immunoreactive amacrine and horizontal cells. Dopamine did not interfere with the kainate effect. While in control and in non-stimulated retinas a continuous and homogeneous immunolabeling was observed throughout the inner plexiform layer, retinas exposed to NMDA, kainate and aspartate displayed only a faint punctate labeling in the inner plexiform layer. It is concluded that, under our experimental conditions, both NMDA and aspartate induce the release of GABA exclusively from amacrine cells, and that the release is modulated by dopamine. On the other hand, kainate stimulates GABA release from both amacrine and horizontal cells with no interference of dopamine.

Amacrine Cells↗

Long-range synchronization of oscillatory light responses in the cat retina and lateral geniculate nucleus.

Visual responses in the retina and the lateral geniculate nucleus (LGN) exhibit oscillatory patterning within a broad range of frequencies. Oscillatory activity is often associated with the synchronization of spatially distributed responses. Here we demonstrate, with simultaneous multi-electrode recordings from the retina and the LGN, that stationary and moving light stimuli evoke in retinal ganglion cells oscillatory responses in the frequency range of 61 to 114 Hz that become synchronized over distances larger than 20 degrees of visual angle across the nasal and temporal halves of the retina. This temporal patterning of retinal responses is transmitted reliably by LGN neurons, such that stimuli crossing the vertical meridian evoke synchronous responses in the LGNs of both hemispheres. The oscillatory responses are not phase-locked to the stimulus onset, indicating that synchronization results from horizontal interactions in the retina. The occurrence of synchronization depends on global stimulus properties such as size and continuity, suggesting that temporal correlation among responses of spatially segregated ganglion cells can be exploited to convey information relevant for perceptual grouping.

Animals↗

Morphological and electrophysiological properties of dissociated primate retinal cells.

Although isolated retinal cell preparations have been used widely to study retinal function in lower vertebrates, dissociated cells from primate retina have not been developed for routine physiological experiments. In this study, we demonstrated the feasibility of obtaining viable and identifiable dissociated cells from the primate retina. In addition, we characterized voltage-dependent membrane currents in each type of primate retinal cell with the whole-cell patch-clamp technique. Multiple types of ionic conductance with distinctive current profiles were recorded in various types of primate retinal neurons. Photoreceptors exhibited an inward I(H) activated by membrane hyperpolarization and an outward current activated at depolarized potentials. Two types of potassium currents (transient potassium current, I(K(A)), and delayed rectifier potassium current, I(K(V))) were recorded from bipolar cells. I(K(A)) dominated the current response in putative midget bipolar cells, and I(K(V)) was mainly associated with putative rod bipolar cells. L-type calcium currents (I(Ca)) were observed in primate bipolar cells with axon terminals, but not in axotomized bipolar cells. Large voltage-dependent sodium currents (I(Na)) were only recorded from ganglion cells. Muller cells exhibited I(K(V)) and large potassium inward rectifier current (I(K(IR))), and occasionally a small I(Na). Neurons with electrophysiological signatures of amacrine cells and horizontal cells were also studied even though their morphological features were lost during cell dissociation. By using both morphological and physiological criteria outlined in this report, it is possible to use the dissociated retinal cell preparation as an in vitro system for physiological, biochemical and pharmacological studies of the primate visual system.

Amacrine Cells↗

Orientation bias of cat retinal ganglion cells.

Kuffler described the receptive fields of cat retinal ganglion cells as having a concentric arrangement. This has usually been taken to mean that they are approximately circular in form (see, for example, ref. 2). Hammond tested the circularity of the centre component of receptive fields by plotting a contour of isosensitivity to a small flashed spot. He concluded that centres were often ellipitical (average ratio of major to minor axis 1.23) and that more than 50% of the recorded cells had the major axis oriented within /+- 20 degrees of the horizontal. Such data are important for discussions of the neurophysiological basis of the 'oblique effect' (reduced visibility for periodic grating patterns when oriented away from the vertical or horizontal) observed in psychophysical experiments on humans because subcortical units are often assumed to be orientationally unbiased. Orientation selectivity is a prominent attribute of visual cortical neurones so analysis has usually emphasized the distribution of orientation selectivity at that level. The results presented here redirect attention to the retinal level since they reveal a previously unsuspected systematic relation between orientation bias of ganglion cells and their location relative to the area centralis.

Action Potentials↗

The organization of the inner nuclear layer of the rabbit retina.

The initial goal of this study was to establish an accounting of the major classes of cells present in the inner nuclear layer (INL) of the rabbit's retina. Series of 80-100 radial sections 1 micron thick were cut from retinal blocks dissected at intervals along the vertical meridian. They were photographed at high magnification in the light microscope. By visualizing the initial segments of processes leaving the somata, we could identify each cell as a bipolar, amacrine, horizontal, or Müller cell. The identifications made by light microscopy were confirmed by electron microscopy of alternating ultrathin sections. On average, bipolar cells made up 41% of the total INL cells, amacrine cells 32%, horizontal cells 1.5%, and Müller cells 24%. These fractions varied relatively little across the retina or among different animals. We next immunolabeled the rod bipolar cells of whole-mounted retinas with antibodies against protein kinase C, using FITC as the visualizing agent. The same retinas were counterstained with a DNA-binding probe that fluoresces at longer wavelengths. Serial optical horizontal sections of the double-labeled wholemounts were made by confocal microscopy. On average, rod bipolars accounted for 10% of the total INL cells. By subtraction, the cone bipolars made up 31% of the total cells. We conclude that cone bipolars substantially outnumber rod bipolars, even in a retina in which rods outnumber cones by more than 20:1. Using the base of reference created here, a similar analysis can be carried out for other subclasses of retinal neuron. Because the analysis does not depend on absolute cell densities or corrections for shrinkage, data acquired by different histochemical techniques may be combined.

Animals↗

Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina.

The receptive field (RF) of retinal ganglion cells (RGCs) consists of an excitatory central region, the RF center, and an inhibitory peripheral region, the RF surround. It is still unknown in detail which inhibitory interneurons (horizontal or amacrine cells) and which inhibitory circuits (presynaptic or postsynaptic) generate the RF surround. To study surround inhibition, light-evoked whole-cell currents were recorded from RGCs of the isolated, intact rabbit retina. The RFs were stimulated with light or dark spots of increasing diameters and with annular light stimuli. Direct inhibitory currents could be isolated by voltage clamping ganglion cells close to the Na(+)/K(+) reversal potential. They mostly represent an input from GABAergic amacrine cells that contribute to the inhibitory surround of ganglion cells. This direct inhibitory input and its physiological function were also investigated by recording light-evoked action potentials of RGCs in the current-clamp mode and by changing the intracellular Cl(-) concentration. The excitatory input of the ganglion cells could be isolated by voltage clamping ganglion cells at the Cl(-) reversal potential. Large light spots and annular light stimuli caused a strong attenuation of the excitatory input. Both GABA(A) receptors and GABA(C) receptors contributed to this inhibition, and picrotoxinin was able to completely block it. Together, these results show that the RF surround of retinal ganglion cells is mediated by a combination of direct inhibitory synapses and presynaptic surround inhibition.

Action Potentials↗

GABA transporters and GABAC-like receptors on catfish cone- but not rod-driven horizontal cells.

The effects of GABA and related agents were studied in solitary rod- and cone-driven horizontal cells, acutely isolated from the catfish retina using enzymatic and mechanical treatment. Both types of horizontal cells, which normally receive glutamatergic input from photoreceptors, responded to pressure ejection of the glutamate analog kainate (50 microM) with an inward current of 300-800 pA when voltage-clamped at -70 mV using the whole-cell patch-clamp technique. But pressure ejection of GABA (500 microM) elicited an inward current only in cone-driven horizontal cells. This current, ranging between 100 and 400 pA, consisted of two components: (1) a GABA receptor-gated chloride current that reversed near the chloride equilibrium potential and was blocked by bath application of picrotoxin (100-500 microM), and (2) a GABA transporter-mediated current that was picrotoxin resistant but was blocked by NO-711 (1 microM) and cis-4-hydroxynipecotic acid (250 microM), two potent GABA transporter blockers. The GABA transporter current could also be eliminated when sodium was replaced by either choline or lithium in the bathing medium. The picrotoxin-sensitive receptor-gated current could not be elicited by the GABAB receptor agonist baclofen, nor could it be blocked by the potent GABAB receptor antagonist 2-hydroxysaclofen. The picrotoxin-sensitive current could be divided into two components based on their sensitivity to the specific GABAA receptor antagonist bicuculline methiodide. The bicuculline-sensitive component was found only in some cells, whereas the bicuculline-resistant, picrotoxin-sensitive component was found in all cells tested. The bicuculline-resistant current was insensitive to pentobarbital, an allosteric modulator of GABAA receptor. To confirm the effectiveness of the specific batch of bicuculline methiodide and pentobarbital, we tested both drugs in ganglion cells in the salamander retinal slice preparation, where the GABA-elicited current is almost exclusively mediated by GABAA receptors. Bicuculline methiodide almost completely blocked, while pentobarbital significantly enhanced, the GABA current recorded in ganglion cells. Thus, in catfish cone horizontal cells the bicuculline-resistant GABA receptor current is most likely mediated by the GABAC receptor based on the above pharmacological profile. The relative effectiveness of GABA, muscimol, trans- and cis-4-aminocrotonic acid (TACA and CACA) was determined at this GABAC receptor site after cells were bathed in choline Ringer to eliminate the transporter current and in the presence of 100 microM bicuculline methiodide to block GABAA receptor current.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Spatiotemporal testing and modeling of catfish retinal neurons.

The responses of retinal neurons depend on the interaction of both temporal and spatial aspects of a light stimulus. We developed a linear spatiotemporal model of receptor and horizontal cell layers in the catfish retina based on reciprocal interactions between both layers and coupling within each. Horizontal cell transfer properties were measured experimentally using white-noise intensity modulated light spots of different diameters and were compared with analytical predictions based on the model. Good agreement was obtained with a reasonable choice of model space-constants and feedback parameters. Furthermore, the same set of parameter values determined from spot experiments enabled accurate prediction of experimental horizontal cell responses to traveling gratings. The proposed feedback connections from horizontal cells to receptors quicken the time-course of responses in both layers and sharpen receptive fields.

Animals↗

The eye and nutrition

Purpose: To examine the effect of vitamins and trace elements on ocular tissue.Materials and Methods: Rats or mice were fed diets deficient in the trace elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B(12), C, and E. In some rats Al and vitamin A were injected in excessive amounts. We studied the conjunctiva, cornea, retina, and optic nerve with a light microscope, transmission and scanning electron microscopes, an energy dispersive X-ray analyzer, and an ion microscope. Histochemical, cytochemical, and immunohistochemical techniques were applied to the pathological specimens.Results: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a loss of goblet cells in the conjunctiva and a prominent decrease of microvilli and microplicae in the conjunctiva and cornea. The elements in the goblet cells were changed in these conditions. In addition, epithelial cells showed poor fibrous development and abnormal distribution of chromatin in the nucleus.Zn, Cu, Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin B(12) deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg deficiency induced multifocal necrosis in the retinal pigment epithelium and apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed abnormal phagocytosis of the photoreceptor outer segment discs in the retinal pigment epithelium. Vitamin B(12) was found to be related to the circadian rhythm in the retina.Deficiencies of Zn, Cu, Mn, and vitamins A, B(12), and E induced degeneration and disappearance of myelin lamellae in the myelinated optic nerve fibers.In hypervitaminosis A, lipid droplets appeared in the retinal pigment epithelium and alcohol dehydrogenase disappeared in the retinal pigment epithelium and photoreceptor outer segments. Excessive Al was toxic to the retina, which showed disappearance of photoreceptor cells. Al deposits were seen in dendrites and neurons in the outer plexiform layer.Zn seemed to be necessary for corneal epithelial cell wound healing.Discussion: Trace elements usually are contained in enzymes, which have many metabolic functions. They are related to synthesis and breakdown of many substances. Some trace elements such as Zn, Cu, Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of lipids. Some vitamins have an affinity for specific tissues such as epithelial cells, nerve fibers, and neuronal cells and are needed for cell differentiation, development, and maintenance.Conclusion: Cu, Zn, Mn, Se, Mg, and Cr and vitamins A, B(12), C, and E are necessary for maintenance of cellular structure and metabolism.

Journal Article↗

The kinetics of tracer movement through homologous gap junctions in the rabbit retina.

Observation of the spread of biotinylated or fluorescent tracers following injection into a single cell has become one of the most common methods of demonstrating the presence of gap junctions. Nevertheless, many of the fundamental features of tracer movement through gap junctions are still poorly understood. These include the relative roles of diffusion and iontophoretic current, and under what conditions the size of the stained mosaic will increase, asymptote, or decline. Additionally, the effect of variations in amount of tracer introduced, as produced by variation in electrode resistance following cell penetration, is not obvious. To examine these questions, Neurobiotin was microinjected into the two types of horizontal cell of the rabbit retina and visualized with streptavidin-Cy3. Images were digitally captured using a confocal microscope. The spatial distribution of Neurobiotin across the patches of coupled cells was measured. Adequate fits to the data were obtained by fitting to a model with terms for diffusion and amount of tracer injected. Results indicated that passive diffusion is the major source of tracer movement through gap junctions, whereas iontophoretic current played no role over the range tested. Fluorescent visualization, although slightly less sensitive than peroxidase reactions, produced staining intensities with a more useful dynamic range. The rate constants for movement of Neurobiotin between A-type horizontal cells was about ten times greater than that for B-type horizontal cells. Although direct extrapolation to ion conductances cannot be assumed, tracer movement can be used to give an estimate of relative coupling rates across cell types, retinal location, or modulation conditions in intact tissue.

Animals↗

The expression of GAD67 isoforms in zebrafish retinal tissue changes over the light/dark cycle.

We show the levels of glutamic acid decarboxylase (GAD), the enzyme catalyzing the conversion of glutamic acid to GABA, changes in zebrafish retinal tissue during the light/dark cycle. Further, we identify two transcripts of the GAD67 gene, full-length GAD67 and the truncated 25 kDa alternative splice variant (ES), as the major GAD isoforms in this tissue. GAD-positive neurons were identified immunocytochemically by probing retinal sections with K2, an antibody to the GAD67 isoform, and with an antibody specific for the 25 kDa splice variant. For both antibodies, GAD-immunoreactivity was observed in horizontal cells in the distal retina and amacrine cells in the proximal retina, with both cell bodies and processes labeled. No apparent difference in K2 labeling pattern was observed in tissue harvested 8 hrs after light offset or onset, whereas ES label was identified in more structures in dark tissue. Quantification of GAD levels was determined by densitometry of Western Blots. The protein content of GAD67 and ES varied between tissue harvested during the light and the dark. ES expression was up-regulated in dark tissue; whereas, full-length GAD67 expression increased in light tissue. In vivo GABA content, measured with high performance liquid chromatography (HPLC), was found to increase in light tissue, paralleling the expression of full-length GAD67 transcripts. Expression of ES did not correlate with measured GABA levels, suggesting this isoform, which lacks the catalytic domain necessary for enzymatic activity, may have a different physiological role in retinal tissue. The inverse expression patterns of full-length GAD67 and ES suggest that alternative splicing of GAD67 may be triggered by the light and/or dark cycle, resulting in a change in inhibitory neurotransmitter content in retinal tissue.

Animals↗

Gaze direction controls response gain in primary visual-cortex neurons.

To localize objects in space, the brain needs to combine information about the position of the stimulus on the retinae with information about the location of the eyes in their orbits. Interaction between these two types of information occurs in several cortical areas, but the role of the primary visual cortex (area V1) in this process has remained unclear. Here we show that, for half the cells recorded in area V1 of behaving monkeys, the classically described visual responses are strongly modulated by gaze direction. Specifically, we find that selectivity for horizontal retinal disparity-the difference in the position of a stimulus on each retina which relates to relative object distance-and for stimulus orientation may be present at a given gaze direction, but be absent or poorly expressed at another direction. Shifts in preferred disparity also occurred in several neurons. These neural changes were most often present at the beginning of the visual response, suggesting a feedforward gain control by eye position signals. Cortical neural processes for encoding information about the three-dimensional position of a stimulus in space therefore start as early as area V1.

Animals↗

The orientation of cell division influences cell-fate choice in the developing mammalian retina.

Asymmetric segregation of cell-fate determinants during cell division plays an important part in generating cell diversity in invertebrates. We showed previously that cells in the neonatal rat retina divide at various orientations and that some dividing cells asymmetrically distribute the cell-fate determinant Numb to the two daughter cells. Here, we test the possibility that such asymmetric divisions contribute to retinal cell diversification. We have used long-term videomicroscopy of green-fluorescent-protein (GFP)-labeled retinal explants from neonatal rats to visualize the plane of cell division and follow the differentiation of the daughter cells. We found that cells that divided with a horizontal mitotic spindle, where both daughter cells should inherit Numb, tended to produce daughters that became the same cell type, whereas cells that divided with a vertical mitotic spindle, where only one daughter cell should inherit Numb, tended to produce daughters that became different. Moreover, overexpression of Numb in the dividing cells promoted the development of photoreceptor cells at the expense of interneurons and Müller glial cells. These findings indicate that the plane of cell division influences cell-fate choice in the neonatal rat retina and support the hypothesis that the asymmetric segregation of Numb normally influences some of these choices.

Animals↗