Research Article
A model of high-frequency oscillatory potentials in retinal ganglion cells
- GARRETT T. KENYON, BARTLETT MOORE, JANELLE JEFFS, KATE S. DENNING, GREG J. STEPHENS, BRYAN J. TRAVIS, JOHN S. GEORGE, JAMES THEILER, DAVID W. MARSHAK
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- Published online by Cambridge University Press:
- 22 January 2004, pp. 465-480
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High-frequency oscillatory potentials (HFOPs) have been recorded from ganglion cells in cat, rabbit, frog, and mudpuppy retina and in electroretinograms (ERGs) from humans and other primates. However, the origin of HFOPs is unknown. Based on patterns of tracer coupling, we hypothesized that HFOPs could be generated, in part, by negative feedback from axon-bearing amacrine cells excited via electrical synapses with neighboring ganglion cells. Computer simulations were used to determine whether such axon-mediated feedback was consistent with the experimentally observed properties of HFOPs. (1) Periodic signals are typically absent from ganglion cell PSTHs, in part because the phases of retinal HFOPs vary randomly over time and are only weakly stimulus locked. In the retinal model, this phase variability resulted from the nonlinear properties of axon-mediated feedback in combination with synaptic noise. (2) HFOPs increase as a function of stimulus size up to several times the receptive-field center diameter. In the model, axon-mediated feedback pooled signals over a large retinal area, producing HFOPs that were similarly size dependent. (3) HFOPs are stimulus specific. In the model, gap junctions between neighboring neurons caused contiguous regions to become phase locked, but did not synchronize separate regions. Model-generated HFOPs were consistent with the receptive-field center dynamics and spatial organization of cat alpha cells. HFOPs did not depend qualitatively on the exact value of any model parameter or on the numerical precision of the integration method. We conclude that HFOPs could be mediated, in part, by circuitry consistent with known retinal anatomy.
Retinal projections in the cat: A cholera toxin B subunit study
- ISABELLE MATTEAU, DENIS BOIRE, MAURICE PTITO
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- 22 January 2004, pp. 481-493
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The B fragment of cholera toxin (CTb) is a highly sensitive anterograde tracer for the labelling of retinal axons. It can reveal dense retinofugal projections to well-known retinorecipient nuclei along with sparse but distinct input to target areas that are not commonly recognized. Following a unilateral injection of CTb into the vitreous chamber of seven adult cats, we localized the toxin immunohistochemically in order to identify direct retinal projections in these animals. Consistent with previous findings, the strongest projections were observed in the superficial layers of the superior colliculus, the dorsal and ventral lateral geniculate nuclei, the pretectal nuclei, the accessory optic nuclei, and the suprachiasmatic nucleus of the hypothalamus. However, we also found labelled terminals in several other brain areas, including the zona incerta, the medial geniculate nucleus, the lateral posterior-pulvinar complex, the lateral habenular nucleus, and the anterior and lateral hypothalamic regions. The morphological characteristics of the retinal axon terminals in most of the identified novel target sites are described.
Video-rate and continuous visual stimuli do not produce equivalent response timings in visual cortical neurons
- TIMOTHY J. GAWNE, JILL M. WOODS
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- 22 January 2004, pp. 495-500
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Video cathode ray tube (CRT) technology has proven to be extremely valuable for performing research in the visual system. However, the image on a CRT monitor is not constant, but consists of a series of brief pulses. This has implications for any study that explores the responses of neurons in the visual system on short time scales. In particular, there is no unambiguous time point at which a visual stimulus presented via CRT may be said to have ended. Recordings from single units in visual cortical area V1 of an awake primate demonstrate that, when studying changes in response timing on the order of 10 ms or less, stimuli delivered at video frame rates do not duplicate the effects seen with stimuli that have continuous functions of luminance versus time. Additionally, there does not seem to be any clear method of comparing the results obtained with video-rate stimuli with results obtained with continuous-time stimuli that holds for all conditions. These effects are especially critical when exploring the time course of the neuronal responses to the ending of a visual stimulus (off-response). Our findings cast doubt upon the recently reported result that off-responses have consistently shorter latencies than on-responses.
Hyper-vision in a patient with central and paracentral vision loss reflects cortical reorganization
- CLARA CASCO, GIANLUCA CAMPANA, ALBA GRIECO, SILVANA MUSETTI, SALVATORE PERRONE
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- 22 January 2004, pp. 501-510
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SM, a 21-year-old female, presents an extensive central scotoma (30 deg) with dense absolute scotoma (visual acuity = 10/100) in the macular area (10 deg) due to Stargardt's disease. We provide behavioral evidence of cortical plastic reorganization since the patient could perform several visual tasks with her poor-vision eyes better than controls, although high spatial frequency sensitivity and visual acuity are severely impaired. Between 2.5-deg and 12-deg eccentricities, SM presented (1) normal acuity for crowded letters, provided stimulus size is above acuity thresholds for single letters; (2) a two-fold sensitivity increase (d-prime) with respect to controls in a simple search task; and (3) largely above-threshold performance in a lexical decision task carried out randomly by controls. SM's hyper-vision may reflect a long-term sensory gain specific for unimpaired low spatial-frequency mechanisms, which may result from modifications in response properties due to practice-dependent changes in excitatory/inhibitory intracortical connections.
Chromatic detection and discrimination in the periphery: A postreceptoral loss of color sensitivity
- JESSICA R. NEWTON, RHEA T. ESKEW
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- 26 January 2004, pp. 511-521
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The peripheral visual field is marked by a deterioration in color sensitivity, sometimes attributed to the random wiring of midget bipolar cells to cone photoreceptors in the peripheral retina (Mullen, 1991; Mullen & Kingdom, 1996). Using psychophysical methods, we explored differences in the sensitivity of peripheral color mechanisms with detection and discrimination of 2-deg spots at 18-deg eccentricity, and find evidence for a postreceptoral locus for the observed loss in sensitivity. As shown before, observers' sensitivity to green was lower than to red in the periphery, although the magnitude of this effect differed across observers. These results suggest that the asymmetry in peripheral sensitivity occurs at a postreceptoral site, possibly a cortical one. In addition, noise masking was used to determine the cone inputs to the peripheral color mechanisms. The masked detection contours indicate that the red and green mechanisms in the periphery respond to the linear difference of approximately equally weighted L- and M-cone contrasts, just as they do in the fovea. Thus, if the midget retinal ganglion system is responsible for red/green color perception in the fovea, it is likely to be responsible at 18-deg eccentricity as well.
Limulus opsins: Diurnal regulation of expression
- JASBIR S. DALAL, ROBERT N. JINKS, CHELSIE CACCIATORE, ROBERT M. GREENBERG, BARBARA-ANNE BATTELLE
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- Published online by Cambridge University Press:
- 22 January 2004, pp. 523-534
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Much has been learned from studies of Limulus photoreceptors about the role of the circadian clock and light in the removal of photosensitive membrane. However, little is known in this animal about mechanisms regulating photosensitive membrane renewal, including the synthesis of proteins in, and associated with, the photosensitive membrane. To begin to understand renewal, this study examines diurnal changes in the levels of mRNAs encoding opsin, the integral membrane protein component of visual pigment, and the relative roles of light and the circadian clock in producing these changes. We show that at least two distinct opsin genes encoding very similar proteins are expressed in both the lateral and ventral eyes, and that during the day and night in the lateral eye, the average level of mRNA encoding opsin1 is consistently higher than that encoding opsin2. Northern blot assays showed further that total opsin mRNA in the lateral eyes of animals maintained under natural illumination increases during the afternoon (9 & 12 h after sunrise) in the light and falls at night in the dark. This diurnal change occurs whether or not the eyes receive input from the circadian clock, but it is eliminated in eyes maintained in the dark. Thus, it is regulated by light and darkness, not by the circadian clock, with light stimulating an increase in opsin mRNA levels. The rise in opsin mRNA levels observed under natural illumination was seasonal; it occurred during the summer but not the spring and fall. However, a significant increase in opsin mRNA levels could be achieved in the fall by exposing lateral eyes to 3 h of natural illumination followed by 9 h of artificial light. The diurnal regulation of opsin mRNA levels contrasts sharply with the circadian regulation of visual arrestin mRNA levels (Battelle et al., 2000). Thus, in Limulus, distinctly different mechanisms regulate the levels of mRNA encoding two proteins critical for the photoresponse.
Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors
- ANNA MÖLLER, THOR EYSTEINSSON
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- 22 January 2004, pp. 535-542
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The separate components of the dark-adapted electroretinogram (ERG) are believed to reflect the electric activity of neurones in both the inner and the outer layers of the retina, although their precise origin still remains unclear. The purpose of this study was to examine whether selective blockage or stimulation of the different subtypes of GABA receptors might help further elucidate the cellular origin of the components of the dark-adapted ERG. The rat retina is of interest since the localization and physiology of GABA receptors in that retina have been examined in great detail. GABA agonists and antagonists, known to affect the responses of neurons in the inner plexiform layer, were injected into the vitreous of one eye while ERG responses evoked by flashes of white light were recorded. GABA and the GABAa agonist isoguvacine completely removed the oscillatory potentials (OPs) and reduced the amplitude of the a- and b-waves. TPMPA, a GABAc antagonist, reduced the a- and b-waves but had no significant effect on the OPs. Baclofen, a GABAb agonist, reduced the amplitude of the a- and b-waves, without having any effects on the amplitude of the OPs. The GABAb antagonist CGP35348 increased the amplitudes of the a- and b-wave without having an effect on the amplitudes of the OPs. The GABAb receptor ligands had significant and opposite effect on the latency of the OPs. These results indicate that retinal neurons, presumably a subpopulation of amacrine cells, that have GABAb receptors are not the source of the OPs of the ERG, although they may modulate these wavelets in some manner, while contributing to the generation of the dark-adapted a- and b-waves. OPs are modified by stimulation of GABAa receptors, and the a- and b-waves by stimulation of all GABA receptor subtypes.
Visual resolution with epi-retinal electrical stimulation estimated from activation profiles in cat visual cortex
- MARCUS WILMS, MARCUS EGER, THOMAS SCHANZE, REINHARD ECKHORN[dagger]
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- 22 January 2004, pp. 543-555
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Blinds with receptor degeneration can perceive localized phosphenes in response to focal electrical epi-retinal stimuli. To avoid extensive basic stimulation tests in human patients, we developed techniques for estimating visual spatial resolution in anesthetized cats. Electrical epi-retinal and visual stimulation was combined with multiple-site retinal and cortical microelectrode recordings of local field potentials (LFPs) from visual areas 17 and 18. Classical visual receptive fields were characterized for retinal and cortical recording sites using multifocal visual stimulation combined with stimulus–response cross-correlation. We estimated visual spatial resolution from the size of the cortical activation profiles in response to single focal stimuli. For comparison, we determined activation profiles in response to visual stimuli at the same retinal location. Activation profiles were single peaked or multipeaked. In multipeaked profiles, the peak locations coincided with discontinuities in cortical retinotopy. Location and width of cortical activation profiles were distinct for retinal stimulation sites. On average, the activation profiles had a size of 1.28 ± 0.03 mm cortex. Projected to visual space this corresponds to a spatial resolution of 1.49 deg ± 0.04 deg visual angle. Best resolutions were 0.5 deg at low and medium stimulation currents corresponding to a visus of 1/30. Higher stimulation currents caused lower spatial, but higher temporal resolution (up to 70 stimuli/s). In analogy to the receptive-field concept in visual space, we defined and characterized electrical receptive fields. As our estimates of visual resolutions are conservative, we assume that a visual prosthesis will induce phosphenes at least at this resolution. This would enable visuomotor coordinations and object recognition in many indoor and outdoor situations of daily life.
Activation of glutamate transporters in rods inhibits presynaptic calcium currents
- KATALIN RABL, ERIC J. BRYSON, WALLACE B. THORESON
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- 23 January 2004, pp. 557-566
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We found that L-glutamate (L-Glu) inhibits L-type Ca2+ currents (ICa) in rod photoreceptors. This inhibition was studied in isolated rods or rods in retinal slices from tiger salamander using perforated patch whole cell recordings and Cl−-imaging techniques. Application of L-Glu inhibited ICa by ∼20% at 0.1 mM and ∼35% at 1 mM. L-Glu also produced an inward current that reversed around ECl. The metabotropic glutamate receptor (mGluR) agonists t-ADA (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on ICa. However, the glutamate transport inhibitor, TBOA (0.1 mM), prevented L-Glu from inhibiting ICa. D-aspartate (D-Asp), a glutamate transporter substrate, also inhibited ICa with significantly more inhibition at 1 mM than 0.1 mM. Using Cl− imaging, L-Glu (0.1–1 mM) and D-Asp (0.1–1 mM) were found to stimulate a Cl− efflux from terminals of isolated rods whereas the ionotropic glutamate receptor agonists NMDA, AMPA, and kainate and the mGluR agonist, 1S,3R-ACPD, did not. Glutamate-evoked Cl− effluxes were blocked by the glutamate transport inhibitors TBOA and DHKA. Cl− efflux inhibits Ca2+ channel activity in rod terminals (Thoreson et al. (2000), Visual Neuroscience17, 197). Consistent with the possibility that glutamate-evoked Cl− efflux may play a role in the inhibition, reducing intraterminal Cl− prevented L-Glu from inhibiting ICa. In summary, the results indicate that activation of glutamate transporters inhibits ICa in rods possibly as a consequence of Cl− efflux. The neurotransmitter L-Glu released from rod terminals might thus provide a negative feedback signal to inhibit further L-Glu release.
Development of contour integration in macaque monkeys
- LYNNE KIORPES, SARAH A. BASSIN
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- 22 January 2004, pp. 567-575
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Studies of visual development show that basic metrics of visual development such as spatial resolution develop over the first 6–9 months in monkeys and over the first 6 or so years in humans. However, more complex visual functions may develop over different, or more protracted, time courses. To address the question of whether global perceptual processing is linked to or otherwise dependent on the development of basic spatial vision, we studied the development of contour integration, a global perceptual task, in comparison to that of grating acuity in macaque monkeys. We find that contour integration develops substantially later than acuity. Contour integration begins to develop at 5–6 months, near the time that acuity development is complete and continues to mature well into the second postnatal year. We discuss this later development in terms poor central efficiency and consider the relevant anatomy and physiology of the developing visual system. We conclude that contour integration is not likely to be limited by the same mechanisms that are permissive to acuity development, and may instead reflect the emergence of function central to V1.
Contour integration in amblyopic monkeys
- PETRA KOZMA, LYNNE KIORPES
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- 22 January 2004, pp. 577-588
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Amblyopia is characterized by losses in a variety of aspects of spatial vision, such as acuity and contrast sensitivity. Our goal was to learn whether those basic spatial deficits lead to impaired global perceptual processing in strabismic and anisometropic amblyopia. This question is unresolved by the current human psychophysical literature. We studied contour integration and contrast sensitivity in amblyopic monkeys. We found deficient contour integration in anisometropic as well as strabismic amblyopic monkeys. Some animals showed poor contour integration in the fellow eye as well as in the amblyopic eye. Orientation jitter of the elements in the contour systematically decreased contour-detection ability for control and fellow eyes, but had less effect on amblyopic eyes. The deficits were not clearly related to basic losses in contrast sensitivity and acuity for either type of amblyopia. We conclude that abnormal contour integration in amblyopes reflects disruption of mechanisms that are different from those that determine acuity and contrast sensitivity, and are likely to be central to V1.