Murine cones contain two opsins in the same cone, one ultraviolet (UV) and the other middle-wavelength sensitive (M). A long-wavelength flash only affecting M-opsin suppresses the cone electroretinogram (ERG) produced by light absorption of UV-cone opsin raising the hypothesis that activation of M-cone opsin suppresses UV-cone opsin responses in the same cone. Here we show that pharmacologic blockade of synaptic transmission in the superfused murine retina, which eliminates interaction from second-order neurons, fails to prevent suppression of the UV-opsin driven pathway by long-wavelength stimuli. This proves that the antagonism must be occurring in the same cone, co-expressing both opsins. Our results show that UV-opsin suppression successively ceases in presence of the M-opsin activating background light, which implies that cone light adaptation is controlled at the opsin stage, before activation of transducin. It also reveals the time course of a transient desensitization of cones due to post-opsin factors in the transduction cascade.

The present work quantifies aspects of photoreceptor structure related to mitochondria, inner segment dimensions, and optical properties, as a basis for furthering our understanding of rod and cone function. Electron-microscopic analyses were performed on the retina of one stumptail macaque (Macaca arctoides) to obtain stereological measurements of ellipsoid mitochondrial density, and sizes and shapes of outer and inner segments. In addition, the distribution of mitochondria and the optical properties of human foveal cones were examined with electron microscopy and Nomarski differential interference contrast (NDIC) imaging. Mitochondria comprised 74–85% of cone ellipsoids and 54–66% of rod ellipsoids in macaque. Ellipsoid volume increased with eccentricity by 2.4-fold for rods and more than 6-fold for cones over eccentricities to 12.75 mm, while the volume of the outer segment supported by the ellipsoid was essentially constant for both rods and cones. Per unit volume of outer segment, cones contained ten times as much mitochondria as rods. In human fovea, as in the rest of the retina, most cone mitochondria were located in the distal inner segment. In the foveal center, however, there are also mitochondria in the myoid, as well as in the outer fiber, proximal to the external limiting membrane (ELM). Analyses of the optical aperture of human foveal cones, the point at which their refractive index clearly differs from the extrareceptoral space, showed that it correlated well with the location of mitochondria, except in the foveal center, where the aperture appeared proximal to the ELM. While mitochondria have an important metabolic function, we suggest that the striking differences between rods and cones in mitochondrial content are unlikely to be determined by metabolic demand alone. The numerous cone mitochondria may enhance the waveguide properties of cones, particularly in the periphery.

An observer locomoting along a straight path sees a pattern of optic flow in which images move approximately radially outward from his heading point. If the observer turns, the optic flow field changes markedly because each object's image now has a component of horizontal motion added to its “optic flow” motion. We tested the responses of 326 cells in the cat's extrastriate area LS (lateral suprasylvian visual area) to movies simulating the optic flow seen during locomotion in a straight line, and during various simulated turns to the left and right. About 60% of 326 cells tested responded to optic flow simulating turns. Of most interest was a subset of cells, 15% of the total, that had “turn-selective” responses. They responded significantly better to turns in a particular direction (usually to the contralateral side) than to turns in the opposite direction or to optic flow simulating straight-ahead locomotion. For each cell, we generated a display of fronto-parallel motion with a direction and speed that matched the image motion in the preferred turn movie, as seen at the receptive-field center. Most turn-selective cells responded significantly better to their preferred turn movie than to this fronto-parallel stimulus. We examined the role of cells' selectivity for stimulus direction, speed, and acceleration in determining cell preference for particular turns. Direction preference played some role for most cells, but about a third of the cells preferred turn movies that did not reflect their direction selectivity. Other factors, including the presence of opposing motion, only rarely appeared to determine cell preferences for particular turn movies.

Previous studies of human contrast adaptation employing visually evoked potentials (VEP) have revealed contradictory results, namely, either a reduction or an enhancement in VEP amplitude. In a cross-adaptation experiment, we explored the possibility that differences in the temporal frequency of adapting and test patterns played a role. Phase-reversing checkerboard stimuli [1-deg check size, temporal frequency 8.5 or 17 reversals per second (rps)] served as adaptation and test pattern with contrasts of 0 or 97%. In 13 subjects, we recorded both retinal (PERG) and cortical (VEP) steady-state responses simultaneously. In a balanced block design, all four combinations of the temporal adaptation and test frequencies were employed. Contrast adaptation reduced the PERG amplitude by about 20% in every temporal condition (P < 0.001). The VEP amplitude was strongly affected by adaptation, but the effect differed in magnitude and sign depending on condition: With identical adaptation and test frequency, amplitude was reduced by 15% (P = 0.07) at 8.5 rps and by 38% at 17 rps (P < 0.05). Adapting at 8.5 rps and testing at 17 rps had a tiny (14%) insignificant effect, whereas adapting at 17 rps and testing at 8.5 rps revealed an amplitude enhancement of 27% (P < 0.05). These strong temporal cross-adaptation effects (in the VEP, but not in the PERG) suggest that the adaptable cortical mechanisms (gain control) can be narrowly tuned in their temporal properties. A sizable adaptation effect can even change its sign when varying the temporal frequency by a factor of two. This finding resolves contradictions between previous VEP adaptation studies and reconciles them with psychophysical findings.

The responses of many ganglion cells in the rabbit retina are mediated, at least in part, by acetylcholine (ACh) acting on neuronal nicotinic acetylcholine receptors (nAChRs). nAChRs are comprised of α and β subunits; three β subunits and nine α subunits of nAChRs have been identified and these subunits can combine to form a large number of functionally distinct nAChR subtypes. We examined the effects of cholinergic agents on the light-evoked responses of ganglion cells to determine which nAChR subtypes mediate the effects of ACh. Extracellular recordings of retinal ganglion cells were made in intact everted eyecup preparations and nicotinic agonists and antagonists were added to the superfusate. While several ganglion cell classes exhibited methyllycaconitine (MLA) sensitivity, the directionally selective (DS) ganglion cells were most sensitive; exposure to 30 nanomolar MLA, a concentration reportedly too low to affect αBgt-insensitive nAChRs, suppressed the stimulus-evoked responses of DS cells without eliminating directional selectivity. Epibatidine, which at low concentrations is an agonist selective for αBgt-insensitive nAChRs, stimulated firing of various cell types including DS ganglion cells at low nanomolar concentrations. The effects of the various agents tested persisted under cobalt-induced synaptic blockade. The low nanomolar MLA and epibatidine sensitivity of DS cells suggests that DS ganglion cells express both αBgt-sensitive and αBgt-insensitive nAChRs. Other ganglion cell types appear to express only αBgt-sensitive nAChRs but not αBgt-insensitive nAChRs.

We recorded activity of single units in macaque monkey primary visual cortex (V1) to define the retinotopic extent of the visual inputs that drive or modulate V1 neuron responses in parafoveal and peripheral (calcarine) cortex. We used high-contrast drifting grating stimuli to define the extent of the area over which responses summate and the extent of the receptive-field surround. We found responses of most V1 cells to summate over 1 deg, with a suppressive surround typically twice that in diameter, though for some cells (even in parafoveal V1) surrounds exceeded 13 deg in diameter. Surprisingly, we found no significant laminar differences in these dimensions or in the strength of surround suppression. We found that surround suppression in most cells arises from both the ends and sides of the receptive field. Our measures indicate that the strongest modulatory input arises from regions immediately adjacent to the excitatory summation area. These physiological measures suggest that the high-contrast summation field of V1 neurons can be accounted for by the sum of lateral geniculate nucleus (LGN) inputs offered to the local cortical column, with monosynaptic lateral connections within area V1 adding the larger dimensions of the low-contrast summation field and the near surround. Neither of these inputs suffice to explain the largest surrounds, which most likely derive from feedback from extrastriate visual areas.

The response properties of postreceptoral sensory neurones are determined by the properties of their input neurones, by intrinsic membrane properties, and by the properties of neurotransmitter receptors on the soma and dendritic tree. We previously showed that inhibitory neurotransmitter (GABAA and glycine) receptors on a well-characterised sensory neurone, the parasol ganglion cell in the primate retina, are segregated towards the distal part of the dendritic tree. Here we studied the distribution of excitatory ionotropic glutamate receptor subunits on the dendrites of parasol cells in the retina of a New World monkey, the marmoset, Callithrix jacchus. Individual ganglion cells were intracellularly injected in an in vitro retinal wholemount preparation. Ionotropic glutamate receptor subunits, including AMPA (GluR1-4), kainate (GluR6/7), NMDA (NR1C2′) subunits, and the orphan receptors δ1 and δ2 were visualized with immunocytochemical methods. Immunoreactive puncta that colocalized with the dendrites of ganglion cells were analyzed using standard and/or confocal light microscopy. Colocalized puncta were present on parasol dendrites for all subunits studied, but their density was much lower (approximately 1/5) than previously reported for inhibitory (GABA and glycine) receptors. Segregation of the glutamate receptor clusters (GluR1, GluR6/7 subunits) to the peripheral dendrites was less marked than that shown for GABA and glycine receptor clusters. No sign of segregation of colocalized puncta to the peripheral part of the dendritic field was seen with antibodies to the GluR2, GluR2/3, GluR4, δ1/2, or NR1C2′ subunits. The results suggest that although there is diverse expression of glutamate receptor subtypes, the glutamatergic synapses form only a small proportion of the total synaptic input to primate ganglion cells. They further suggest that the processes which control distribution of excitatory and inhibitory synapses on the dendritic field of ganglion cells are, at least to some extent, independent.

The retinas of anchovies have two unique photoreceptor types: “bifid” and “long” cones (Fineran & Nicol, 1976). The outer segments of these cells contain multiple layers of membranes (lamellae) oriented longitudinally (axially). This orientation is distinct from that in all other vertebrate rods and cones, where the lamellae are stacked transversely with their planes perpendicular to the incident light path. Although the common arrangement provides optimal absorption for normally incident light rays, it is also insensitive to the rays' direction of vibration (i.e. their polarization). In contrast, the two mutually perpendicular sets of axially oriented lamellae segregated into bifid and long cones could function as the principal analyzers for linearly polarized light, as previously hypothesized (Fineran & Nicol, 1976, 1978). Here, we report on a microspectrophotometric study that shows (1) the presence of two spectrally distinct visual pigments in the three photoreceptor types of the bay anchovy retina; these are typical vertebrate pigments in that they bleach, when exposed to light, and have absorption spectra like all other vitamin A1-based visual pigments; (2) that the rods and cones exhibit dichroic absorption of light in accordance with their lamellar orientation, and (3) that the two cone types of the retina contain a spectrally indistinguishable pigment with peak absorbance (λmax) around 540 nm, while the rods contain a rhodopsin-like pigment with λmax near 500 nm. Compared to other vertebrates, anchovies are remarkable for using a monochromatic cone system with unusual specializations supportive of a polarization detection system.

The aim of this study was to assess the plasticity of human voluntary fixational eye movement control in relation to visual experience/chronic visual deprivation. Twelve blind adults participated (self-reported vision ≤ light perception in each eye; age range = 23–56 years; visual experience range = 0–28 years; blindness duration range = 6–55 years). Infrared-based recordings of horizontal eye movements were made before, during, and immediately after three 30-s periods of auditory ocular motor feedback, while participants were instructed to look straight ahead and keep their eyes as steady as possible. Percent change in horizontal displacement of the eye during and after feedback was compared with the no-feedback baseline. Eleven of the 12 individuals demonstrated feedback-mediated increase in eye stability, which improved as a function of visual experience. Improved eye stability was inversely related to duration of blindness. Clearly, blind adults can use nonvisual external feedback to stabilize gaze. Thus, the fixational subsystem can exhibit improved voluntary control despite chronic visual deprivation. Possible cortical and subcortical mechanisms are discussed.

Ganglion cells in an isolated wholemount preparation of the rat retina were labeled using the “DiOlistic” labeling method (Gan et al., 2000) and were classified according to their morphological properties. Tungsten particles coated with a lipophilic dye (DiI) were propelled into the wholemount retina using a gene gun. When a dye-coated particle contacted the cell membrane, the entire cell was labeled. The ganglion cells were classified into four types based on their soma size, dendritic-field size, branching pattern, and level of stratification. Broadly monostratified cells were classified into three types: RGA cells (large soma, large dendritic field); RGB cells (small- to medium-sized soma, small- to medium-sized dendritic field); and RGC cells (small- to medium-sized soma, medium-to-large dendritic field). Bistratified cells were classified as RGD. Several subtypes were identified within each ganglion cell group. A number of new subtypes were discovered and added into the existing catalog, among them were two types of bistratified cells. This study therefore represents the most complete morphological classification of rat retinal ganglion cells available to date.

The effects of intraocular injections of ethylcholine mustard aziridinium ion (AF64A), an irreversible inhibitor of choline uptake, on the rabbit retina were assessed electrophysiologically, pharmacologically, anatomically, and behaviorally. Survival times from 1 day to 30 days were investigated. After 24 h, the shortest time tested, the directional selectivity of On–Off responding ganglion cells having the characteristic morphology of On–Off directionally selective directionally selective (DS) ganglion cells, as revealed by intracellular dye injection, was significantly reduced, both by an apparent decrease of preferred direction responses and an increase in responses to null-direction movement. No toxin-mediated changes in the dendritic trees of these cells were noted. Cells in AF64A-affected retinas having the DS morphology did not respond significantly to GABAergic or cholinergic agents such as picrotoxin and eserine, but did respond to nicotine. Recordings from a small random sample of other ganglion cell classes in the same retinas yielded no obvious changes in response properties. The direct effects on starburst (cholinergic) amacrine cells, which were identified by intraocular injection of the fluorescent dye DAPI with the AF64A, were investigated by intracellular injections of Lucifer yellow, and by immunohistochemical staining with antibodies to choline acetyltransferase (ChAT). Although starburst amacrine cell somas survived the AF64A treatment for at least several days, the dendrites could not be visualized by fluorescent dye injection in affected retinas due to dye leakage of the injected fluorescent dye from either the soma or proximal dendritic region. ChAT staining revealed a sequence in which ChAT-positive cells were undetectable first in the inner nuclear layer, and then in the ganglion cell layer. Cholinergic amacrine cells in the central retina were also affected before those in the periphery. The electrophysiological changes observed typically preceded the loss of ChAT activity. Behavioral tests for optokinetic nystagmus responses also revealed a lack of such responses in the affected eyes.

Cells of the cat's perigeniculate nucleus (PGN), part of the visual sector of the thalamic reticular nucleus (TRN), provide GABAergic inhibition to the A and A1 layers of the dorsal lateral geniculate nucleus (LGNd) and, therefore, may control information flow from the retina to the cortex. Previous electrophysiological experiments suggested that the PGN may be subdivided on the basis of ocular dominance thus reflecting the afferent and efferent projections with lamina A and A1 of the LGNd. The present study utilized the ability of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) to be transported transneuronally following intraocular injections in four cats to examine whether there is any anatomical evidence for eye specific layers within the PGN. Sections were processed with tetramethylbenzidine. Light WGA-HRP transneuronal labeling of LGNd collaterals and somata were seen in the PGN and very light labeling (but not somata) was seen in the TRN. Neither the cells of the PGN projecting to the LGNd nor the LGNd relay collaterals within the PGN were clearly organized into nonoverlapping laminae related to the eye specific layers of the LGNd. However, parts of the PGN immediately adjacent to the LGNd appear devoid of connections with lamina A1 thus creating a thin monocular segment for the contralateral eye.

APB (DL-2-amino-4-phosphonobutyric acid) has been found to affect the retinal processing of many vertebrate species as evidenced by the suppression of the b-wave component of the electroretinogram (ERG). The present study examined the effects of APB on the cone contributions to the ERG response of adult zebrafish (Danio rerio). ERG responses were obtained from light-adapted adult zebrafish following intravitreal injection of either saline alone or saline with various concentrations of APB ranging from 10 μm to 500 μM. Visual stimuli were 200-ms flashes of various wavelengths and irradiances. Spectral sensitivity functions were calculated from the irradiance versus response amplitude functions of the a-, b-, and d-wave components of the ERG response. Saline had no effects on the ERG response. However, APB had differential effects on the sensitivity of the b- and d-wave components. The effects of APB on the b-wave component were most apparent in the ultraviolet and short-wavelength portions (320–440 nm) of the spectral sensitivity function, although the b-wave was not completely eliminated at these wavelengths. APB-treated subjects were found to possess the same cone mechanisms (L-M and M-S) in the middle- and long-wavelength areas of the spectrum as saline injected subjects, although absolute sensitivity was lower for the APB-injected subjects. Spectral sensitivity based on the d-wave response was affected by APB but only in the short-wavelength region. All results appear to be independent of the APB dose. These results support the notion that glutamate receptors play a specific role in zebrafish visual processing. In addition, the effects of APB support recent anatomical evidence that the zebrafish retina may possess different types of glutamate receptors.

High levels of endogenous cholecystokinin (CCK) are present in the rat retina (Eskay & Beinfeld, 1982), but the cellular localization and physiological actions of CCK in the rat retina are uncertain. The goals of this study were to characterize the cells containing CCK, identify cell types that interact with CCK cells, and investigate the effects of CCK on rod bipolar cells. Rat retinas were labeled with antibody to gastrin-CCK (gCCK) using standard immunofluorescence techniques. Patch-clamp methods were used to record from dissociated rod bipolar cells from rats and mice. Gastrin-CCK immunoreactive (-IR) axons were evenly distributed throughout the retina in stratum 5 of the inner plexiform layer of the rat retina. However, the gCCK-IR somata were only detected in the ganglion cell layer in the peripheral retina. The gCCK-IR cells contained glutamate decarboxylase, and some of them also contained immunoreactive substance P. Labeled axons contacted PKC-IR rod bipolar cells, and recoverin-IR ON-cone bipolar cells. CCK-octapeptide inhibits GABAC but not GABAA mediated currents in dissociated rod bipolar cells.

We report a unique anomaly in the ocular dominance column pattern of a single, normally pigmented macaque monkey. The column pattern contained large monocular areas inserted between the normal columns and the dorsal V1 border. These monocular regions received transneuronal input from the contralateral eye, indicating that a small population of temporal ganglion cells erroneously decussated at the optic chiasm. Projection of the column pattern back onto the visual field showed that the monocular wedges represented a ∼5-deg sector of ipsilateral field. This corresponded to the extent of naso-temporal overlap of ganglion cells in the normal retina, suggesting an error in axon guidance affecting cells close to the vertical midline of the retina. The consequences of the crossing error in this animal were threefold: it produced an anomalous monocular zone near the V1 border, the vertical meridian was not represented at the V1 border, and points near the vertical meridian were represented twice in the brain, once in each hemisphere.

(Article appeared in Visual Neuroscience (2002), 19, 257–264.)

Due to a production error, we are reprinting the following article because the color images were printed in black and white. The color images are so very important to the understanding of this article, we are reprinting it here with the color images in place.