Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones—in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to study cone elongation on the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1–4 at the developing fovea, and three other sample locations on the horizontal meridian. Labeled RNA was detected using the fluorescent marker “Fast Red” (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.

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 Ca2+ 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 μM of SR95531, an antagonist of GABAA receptors, alone did not produce any change in the holding currents. When 200 μM 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 μM of kainate, while the amplitude decreased when the horizontal cells were hyperpolarized by the application of 10 μM of CNQX. When the cone photoreceptors were voltage clamped at a potential at which the voltage-gated Ca2+ 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 Ca2+ currents in cone photoreceptors is a physiologically relevant mechanism for horizontal-cone feedback.

The image on the retina is almost never static. Eye, head, and body movements, and externally generated motion create rapid and continual changes in the retinal image (“active vision”). Virtually all vision in animals such as primates, which make saccades as often as 3–4 times/s, is based on information that must be derived from the first few hundred milliseconds after sudden, global changes in the retinal image. These changes may be accompanied by large changes in area mean luminance, as well as higher order image contrast statistics. This study investigated how retinal ganglion cell responses, whose response properties have been typically studied and defined in a stable stimulus regime, are affected by sudden changes in mean luminance that are characteristic of active vision. Specifically, the steady-state responses of retinal ganglion cells to static or moving square-wave grating stimuli were recorded in an isolated, superfused rabbit eyecup preparation and compared to responses after saccade-like changes in luminance. The manner of coding after luminance changes was different for different ganglion cell classes; both suppression and enhancement of responses to patterns following luminance changes were found. Brisk-transient Off cells unambiguously signaled the darkening of the overall image, but were also modulated by the subsequently appearing grating stimulus. Several types of On-center cell behavior were observed, ranging from strong suppression of the subsequent response by luminance changes, to strong enhancement. Overall, most ganglion cells distinguished static patterns after a luminance change via differences in their spike discharges nearly as well as before, although there were clear asymmetries between the On and Off pathways. Changes in mean luminance in some ganglion cells, such as On–Off directionally selective ganglion cells, could create large phase shifts in the response to patterned, moving stimuli, although these stimuli were still detected immediately after luminance changes. The results of this study show that the image dynamics of active vision may be a fundamental challenge for the visual system because of strong effects on retinal ganglion cell function. However, rapid extraction of unambiguous information after luminance changes appears to be encoded in differences in the spike discharges in different retinal ganglion cell classes. Asymmetries among ganglion cell classes in sensitivity to luminance changes may provide a basis by which some provide the “context” for interpreting the firing of others.

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

Psychophysical measurements using achromatic grating resolution acuity in peripheral vision show a prominent retinal asymmetry in acuity which is consistent with predicted values based on available estimates of midget ganglion cell density. Recent studies have shown that peripheral grating resolution acuity values for short-wavelength-sensitive (SWS) isolating gratings in normal observers are closely related to predicted values based on the underlying small bistratified ganglion cell density. By measuring SWS resolution acuity at different locations across the visual field, we wished to see if any significant acuity asymmetry exists for the short-wavelength system. In addition to this, we wanted to compare SWS and achromatic resolution acuity at different retinal locations of equal eccentricity. SWS and achromatic grating resolution acuity was measured in two observers at a number of different retinal meridians of 10- and 25-deg eccentricity from the fovea, and out to 35-deg eccentricity along the horizontal meridian. Achromatic resolution acuity was higher than SWS resolution acuity at all locations. At 10-deg eccentricity there was slight radial asymmetry in SWS and achromatic acuity, both displaying highest acuity along the horizontal meridian. At 25-deg eccentricity, SWS and achromatic acuity showed significant asymmetry with acuity being higher in the nasal retina compared to the temporal retina and with higher acuity in the superior retina compared to the inferior retina. At 35-deg eccentricity, the acuity asymmetry along the horizontal meridian was maintained with acuity for both significantly higher in the nasal retina. The SWS acuity changes with eccentricity and meridian were qualitatively similar to that found for achromatic acuity at the majority of retinal locations. Like achromatic acuity, SWS acuity shows significant asymmetry at different retinal locations of equal eccentricity. This suggests that both the midget and small bistratified ganglion cell population density changes significantly with retinal location and eccentricity. SWS acuity appears to change in parallel with achromatic acuity for the majority of retinal locations measured, although the amount of nasotemporal asymmetry appears to be slightly less for the SWS system at 25- and 35-deg eccentricity.

Neurones activated through the corpus callosum (CC) in the cat visual cortex are known to be almost entirely located at the 17/18 border. They are orientation selective and display receptive fields (RFs) distributed along the central vertical meridian of the visual field (“visual midline”). Most of these cells are binocular, and many of them are activated both from the contralateral eye through the CC, and from the ipsilateral eye via the direct retino-geniculo-cortical (GC) pathway. These two pathways do not carry exactly the same information, leading to interocular disparity between pairs of RFs along the visual midline. Recently, we have demonstrated that a few weeks of unilateral paralytic strabismus surgically induced at adulthood does not alter the cortical distribution of these units but leads to a loss of their orientation selectivity and an increase of their RF size, mainly toward the ipsilateral hemifield when transcallosally activated (Watroba et al., 2001). To investigate interocular disparity, here we compared these RF changes to those occurring in the same neurones when activated through the ipsilateral direct GC route. The 17/18 transition zone and the bordering medial region within A17 were distinguished, as they display different interhemispheric connectivity. In these strabismics, some changes were noticed, but were basically identical in both recording zones. Ocular dominance was not altered, nor was the spatial distribution of the RFs with respect to the visual midline, nor the amplitude of position disparity between pairs of RFs. On the other hand, strabismus induced a loss of orientation selectivity regardless of whether neurones were activated directly or through the CC. Both types of RFs also widened, but in opposite directions with respect to the visual midline. This led to changes in incidences of the different types of position disparity. The overlap between pairs of RFs also increased. Based on these differences, we suggest that the contribution of the CC to binocular vision along the midline in the adult might be modulated through several intrinsic cortical mechanisms.

Primary open angle glaucoma (POAG) is a leading cause of late onset, progressive, irreversible blindness and, although its etiology is poorly understood, elevated intraocular pressure (IOP) often appears to be a contributory factor. Proteomic and Western analyses of trabecular meshwork (TM) from patients with POAG and age-matched controls originally implicated cochlin as possibly contributing to glaucoma pathogenesis. Cochlin deposits were subsequently detected in glaucomatous but not in control TM and older glaucomatous TM was found to contain higher levels of cochlin and significantly lower amounts of collagen type II. More recently, similar results were reported in DBA/2J mice, which at older ages develop elevated IOP, retinal ganglion cell degeneration, and optic nerve damage. Notably, cochlin was absent in TM from C57BL/6J, CD1, and BALBc/ByJ mice, which do not exhibit elevated IOP or glaucoma. Cochlin was found in the TM of very young DBA/2J mice, prior to elevated IOP, suggesting that over time the protein may contribute to the events leading to increased IOP and optic nerve damage. Here we review these findings and describe how future studies in DBA/2J mice can help resolve whether cochlin plays a causal role in mechanisms of POAG and elevated IOP.

Key indicators of circadian regulation include the persistence of physiological rhythmicity in the absence of environmental time cues and entrainment of this rhythmicity by the ambient light cycle. In some teleosts, the inner segments of rod and cone photoreceptors contract and elongate according to changes in ambient lighting and the circadian cycle. Pigment granules in the retinal pigment epithelium (RPE) disperse and aggregate in a similar manner. Collectively, these movements are known as retinomotor movements. We report the histological characterization of diurnal and circadian retinomotor movements in zebrafish, Danio rerio. Adult fish subjected to a 14:10 light:dark (LD) cycle, constant darkness (DD), or constant light (LL) were sacrificed at 1–13 h intervals and processed for semithin sectioning of the retina. Using bright-field microscopy, 15 measurements of pigment granule position and the inner segment lengths of 30 rods and 30–45 cones were collected from the central third of the dorso-optic retina per time point. In LD, rods and cones followed a clear diurnal rhythm in their inner segment movements. Short-single, UV-sensitive cones were found to contract significantly 1 h before light onset in LD conditions. In DD conditions, the inner segments movements of short-single and double cones displayed statistically significant rhythms. RPE pigment granule movements are rhythmically regulated in both LD and DD although fluctuations are damped in the absence of photic cues. No significant retinomotor movements were observed in LL. These findings indicate retinomotor movements in zebrafish are differentially regulated by an endogenous oscillator and by light-dependent mechanisms.

Termination of GABA signals within the retina occurs through high-affinity reuptake of the released neurotransmitter by GABA transporters (GATs) present in neurons and glia surrounding the release site. In the present work, we have cloned a novel GAT from the retina of the skate (Raja erinacea). The clone codes for a 622 amino acid protein whose sequence has highest similarity to the GABA/β-alanine transporter of the electric ray (Torpedo marmorata) (88% identity) and the GAT-3 isolated from rat brain (75% identity). The protein was expressed in Xenopus oocytes and characterized using the two-electrode voltage-clamp technique. Application of GABA induced a dose-dependent inward current, with 8 μM GABA producing a half-maximal response. The current required the presence of extracellular sodium and was unaffected by the GABA receptor blocker picrotoxin or the GAT-1 specific antagonist NO-711. The high homology between the cloned skate GABA transporter and the GAT-3 equivalents of other species, coupled with the strikingly similar pharmacological profile to GAT-3s of other species, lead us to conclude that we had cloned the GAT-3 homologue for the skate. Polyclonal antibodies specific to GAT-3 and the previously cloned skate GAT-1 transporter were used to examine the distribution of GAT-3 and GAT-1 immunoreactivity in the retina and in isolated cells of the skate. Antibodies for both transporters showed labeling in the outer and inner plexiform layers, and staining extended from the outer to inner limiting membranes. Both GAT-1 and GAT-3 antibodies labeled enzymatically isolated Müller cells, while bipolar cells and horizontal cells did not appear to express either transporter. These results imply that GAT-1 and GAT-3 are both present in Müller cells of the skate retina where they are likely involved in regulating extracellular concentrations of GABA.

The separation of OFF pathways that signal light decrements from ON pathways that signal light increments occurs at the first retinal synapse. The dendrites of OFF bipolar cells abut the cone pedicle at basal positions distal to the site of glutamate release and express ligand-gated or ionotropic glutamate receptors (GluR). The dendrites of ON bipolar cells penetrate narrow invaginations of the cone pedicle proximal to the site of release and express the G-protein-coupled, metabotropic glutamate receptor, mGluR6. However, recent studies demonstrating the expression of GluR subunits in the rodent rod bipolar cell, known to yield an ON response to light, call this basic segregation of receptors into question. The light-microscopic distribution of many glutamate receptors in the primate retina is now well established. We reexamined their ultrastructural localization in the outer retina of Macaca fascicularis to test systematically whether invaginating dendrites at the cone synapse, presumably from ON bipolar cells, also express one or more ionotropic subunits. Using preembedding immunocytochemistry for electron microscopy, we quantified the distribution of the AMPA-sensitive subunits GluR2/3 and GluR4 and of the kainate-sensitive subunits GluR6/7 across 207 labeled dendrites occupying specific morphological loci at the cone pedicle. We report, in agreement with published investigations, that the majority of labeled processes for GluR2/3 (70%) and GluR4 (67%) either occupy basal positions or arise from horizontal cells. For GluR6/7, we find a significantly lower fraction of labeled processes at these positions (47%). We also find a considerable number of labeled dendrites for GluR2/3 (10%), GluR4 (21%), and GluR6/7 (18%) at invaginating positions. Surprisingly, for each subunit, the remainder of labeled processes corresponds to “fingers” of presynaptic cytoplasm within the cone invagination.

Cortical neurons selective for the direction of motion often exhibit some limited response to motion in their nonpreferred directions. Here we examine the dependence of neuronal direction selectivity on stimulus contrast, both for first-order (luminance-modulated, sine-wave grating) and second-order (contrast-modulated envelope) stimuli. We measured responses from single neurons in area 18 of cat visual cortex to both kinds of moving stimuli over a wide range of contrasts (1.25–80%). Direction-selective contrast response functions (CRFs) were calculated as the preferred-minus-null difference in average firing frequency as a function of contrast. We also applied receiver operating characteristic analysis to our CRF data to obtain neurometric functions characterizing the potential ability of each neuron to discriminate motion direction at each contrast level tested. CRFs for sine-wave gratings were usually monotonic; however, a substantial minority of neurons (35%) exhibited nonmonotonic CRFs (such that the degree of direction selectivity decreased with increasing contrast). The underlying preferred and nonpreferred direction CRFs were diverse, often having different shapes in a given neuron. Neurometric functions for direction discrimination showed a similar degree of heterogeneity, including instances of nonmonotonicity. For contrast-modulated stimuli, however, CRFs for either carrier or envelope contrast were always monotonic. In a given neuron, neurometric thresholds were typically much higher for second- than for first-order stimuli. These results demonstrate that the degree of a cell's direction selectivity depends on the contrast at which it is measured, and therefore is not a characteristic parameter of a neuron. In general, contrast response functions for first-order stimuli were very heterogeneous in shape and sensitivity, while those for second-order stimuli showed less sensitivity and were quite stereotyped in shape.

Effects of anesthesia on the blood glucose of C57/BL6J mice were evaluated under conditions commonly used for testing retinal sensitivity with electroretinographic (ERG) recordings. We evaluated the effects of four anesthetics: nembutal (50 mg/kg), pentothal (100 mg/kg), avertin (240 mg/kg), and ketamine/xylazine (100 mg/kg) using saline as control. We measured blood glucose (BG) levels from tail vein blood before and 15 and 60 min following intraperitoneal injections. Fifteen minutes postinjection, all four anesthetics and saline elevated BG with ketamine/xylazine and avertin having substantially greater effects than nembutal, pentothal, and saline. Only the effects of ketamine/xylazine and avertin persisted throughout the test period. Sixty minutes after injecting ketamine/xylazine BG remained elevated at 400 ± 42 mg/dl, a 167% increase over preinjection levels. Sixty minutes after injecting avertin BG was 288 ± 10 mg/dl, a 59% increase over preinjection levels. No sustained elevation in BG was detected 60 min following injection of nembutal, pentothal, or saline. Because BG can affect the amplitude of the ERG, caution should be exercised in the use of ketamine/xylazine or avertin. The choice of anesthesia may also be important in diabetes and metabolism research where changes in blood glucose could impact physiological processes.

Amacrine cells in the external plexiform layer of the fly's lamina have been intracellulary recorded and dye-filled for the first time. The recordings demonstrate that like the lamina's short photoreceptors R1–R6, type 1 lamina amacrine neurons exhibit nonspiking, “sign-conserving” sustained depolarizations in response to illumination. This contrasts with the sign-inverting responses that typify first-order retinotopic relay neurons: monopolar cells L1–L5 and the T1 efferent neuron. The contrast frequency tuning of amacrine neurons is similar to that of photoreceptors and large lamina monopolar cells. Initial observations indicate that lamina amacrine receptive fields are also photoreceptor-like, suggesting either that their inputs originate from a small number of neighboring visual sampling units (VSUs), or that locally generated potentials decay rapidly with displacement. Lamina amacrines also respond to motion, and in one recording these responses were selective for the orientation of moving edges. This functional organization corresponds to the anatomy of amacrine cells, in which postsynaptic inputs from several neighboring photoreceptor endings are linked by a network of very thin distal processes. In this way, each VSU can receive convergent inputs from a surround of amacrine processes. This arrangement is well suited for relaying responses to local intensity fluctuations from neighboring VSUs to a central VSU where amacrines are known to be presynaptic to the dendrites of the T1 efferent. The T1 terminal converges at a deeper level with that of the L2 monopolar cell relaying from the same optic cartridge. Thus, the localized spatial responses and receptor-like temporal response properties of amacrines are consistent with possible roles in lateral inhibition, motion processing, or orientation processing.

Transgenic coneless mice were initially developed to study retinal function in the absence of cones. In coneless mice created by expressing an attenuated diphtheria toxin under the control of flanking sequences from the human L-cone opsin gene, a small number of cones (3–5% of the normal complement) survive in a retina that otherwise appears structurally quite normal. These cones predominantly (∼87% of the total) contain UV-sensitive photopigment. ERG recordings, photoreceptor labeling, and behavioral measurements were conducted on coneless and wild-type mice to better understand how the nature of this alteration in receptor complement impacts vision. Signals from the small residual population of UV cones are readily detected in the flicker ERG where they yield signal amplitudes at saturation that are roughly proportional to the number of surviving cones. Behavioral measurements show that rod-based vision in coneless mice does not differ significantly from that of wild-type mice, nor does their rod system show any evidence of age-related deterioration. Coneless mice are able to make accurate rod-based visual discriminations at light levels well in excess of those required to reach cone threshold in wild-type mice.

Many neurons in the primary visual cortex (area V1) show pronounced selectivity for the orientation and spatial frequency of visual stimuli, whereas most neurons in subcortical afferent streams show little selectivity for these stimulus attributes. It has been suggested that this transformation is a functional sign of increased coding efficiency, whereby the redundancy (or overlap in response properties) is reduced at consecutive levels of visual processing. Here we compared experimentally the response redundancy in area V1 with that in the three main dorsal thalamic afferent streams, the parvocellular (PC), koniocellular (KC), and magnocellular (MC) divisions of the dorsal lateral geniculate nucleus (LGN) in marmosets. The spatial frequency and orientation tuning of single cells in the LGN and area V1 were measured, using luminance contrast sine-wave gratings. A joint spatial frequency-orientation response selectivity profile was calculated for each cell. Response redundancy for each population was estimated by cross-multiplication of the joint selectivity profiles for pairs of cells. We show that when estimated in this way, redundancy in LGN neurons is approximately double that of neurons in cortical area V1. However, there are differences between LGN subdivisions, such that the KC pathway has a spatial representation that lies between the redundant code of the PC and MC pathways and the more efficient sparse spatial code of area V1.

We performed genome-wide mutagenesis of C57BL/6J mice using the mutagen N-ethyl-N-nitrosourea (ENU) and screened the third generation (G3) offspring for visual system alterations using electroretinography and fundus photography. Several mice in one pedigree showed characteristics of retinal degeneration when tested at 12–14 weeks of age: no recordable electroretinogram (ERG), attenuation of retinal vessels, and speckled pigmentation of the fundus. Histological studies showed that the retinas undergo a photoreceptor degeneration with apoptotic loss of outer nuclear layer nuclei but visual acuity measured using the optomotor response under photopic conditions persists in spite of considerable photoreceptor loss. The Noerg-1 mutation showed an autosomal dominant pattern of inheritance in progeny. Studies in early postnatal mice showed degeneration to occur after formation of partially functional rods. The Noerg-1 mutation was mapped genetically to chromosome 6 by crossing C57BL/6J mutants with DBA/2J or BALB/cJ mice to produce an N2 generation and then determining the ERG phenotypes and the genotypes of the N2 offspring at multiple loci using SSLP and SNP markers. Fine mapping was accomplished with a set of closely spaced markers. A nonrecombinant region from 112.8 Mb to 115.1 Mb was identified, encompassing the rhodopsin (Rho) coding region. A single nucleotide transition from G to A was found in the Rho gene that is predicted to result in a substitution of Tyr for Cys at position 110, in an intradiscal loop. This mutation has been found in patients with autosomal dominant retinitis pigmentosa (RP) and results in misfolding of rhodopsin expressed in vitro. Thus, ENU mutagenesis is capable of replicating mutations that occur in human patients and is useful for generating de novo models of human inherited eye disease. Furthermore, the availability of the mouse genomic sequence and extensive DNA polymorphisms made the rapid identification of this gene possible, demonstrating that the use of ENU-induced mutations for functional gene identification is now practical for individual laboratories.

Contextual influences shape our perception of local visual stimuli. Relative-motion stimuli represent an important contextual influence, yet the mechanism subserving relative-motion computation remains largely unknown. In the present work, we investigated the responses of an established model for simple and complex cells to relative-motion stimuli. A straightforward mathematical analysis showed that relative-motion computation is inherent in the nonlinear transformation of the complex-cell model. Tuning to relative velocity is achieved by applying a temporal filter to the complex-cell response. The mathematical inference is supported by simulations that quantitatively reproduce measured complex-cell responses in both cat and monkey to a variety of relative-motion stimuli. Importantly, the posited mechanism for cortical computation of relative motion does not require an intermediate neural representation of local velocities and does not require lateral or feedback interactions within a network.

The superficial layers of the frog optic tectum receive a projection from the contralateral eye that forms a point-to-point map of the visual field. The monocular part of the visual field of the contralateral eye is represented in the caudolateral region of the tectum while the binocular part of the visual field is represented in the rostromedial tectum. Within the representation of the binocular field (rostromedial tectum), the maps of visual space from each eye are aligned. The tectal representation of the binocular visual field of the ipsilateral eye is mediated through a crossed projection from the midbrain nucleus isthmi. This isthmotectal projection also terminates in the caudolateral region of the optic tectum, yet there has been no indication that it forms a functional connection. By extracellular recording in intermediate layer 7 of the caudolateral tectum, we have discovered electrical activity driven by visual stimulation in the monocular visual field of the ipsilateral eye. The units driven from the ipsilateral eye burst upon initial presentation of the stimulus. At individual layer 7 recording sites in the caudolateral tectum, the multiunit receptive field evoked from the ipsilateral eye is located at the mirror image spatial location to the multiunit receptive field driven by the contralateral eye. Thus, as revealed electrophysiologically, there are superimposed topographic maps of the monocular visual fields in the caudolateral tectum. The ipsilateral eye monocular visual field representation can be abolished by electrolytic ablation of contralateral nucleus isthmi.

A new tissue slice preparation of the cuttlefish eye is described that permits patch-clamp recordings to be acquired from intact photoreceptors during stimulation of the retina with controlled light flashes. Whole-cell recordings using this preparation, from the retinas of very young Sepia officinalis demonstrated that the magnitude, latency, and kinetics of the flash-induced photocurrent are closely dependent on the magnitude of the flash intensity. Depolarizing steps to voltages more positive than −40 mV, from a membrane holding potential of −60 mV, induced a transient inward current followed by a larger, more sustained outward current in these early-stage photoreceptors. The latter current resembled the delayed rectifier (IK) already identified in many other nerve cells, including photoreceptors. This current was activated at −30 mV from a holding potential of −60 mV, had a sustained time course, and was blocked in a dose-dependent manner by tetraethylammonium chloride (TEA). The smaller, transient, inward current appeared at potentials more positive than −50 mV, reached peak amplitude at −30 mV and decreased with further depolarization. This current was characterized as the sodium current (INa) on the basis that it was inactivated at holding potentials above −40 mV, was blocked by tetrodotoxin (TTX) and was insensitive to cobalt.

Intracellular perfusion of the photoreceptors, via the patch pipette, demonstrated that U-73122 and heparin blocked the evoked photocurrent in a dose-dependent manner, suggesting the involvement of the phospholipase C (PLC) and inositol 1,4,5-triphosphate (InsP3), respectively, in the phototransduction cascade. Perfusion with cyclic GMP increased significantly the evoked photocurrent, while the inclusion of phorbol-12,13-dibutyrate reduced significantly the evoked photocurrent, supporting the involvement of cGMP and the diacylglycerol (DAG) pathways, respectively, in the cuttlefish transduction process.

Electroretinogram (ERG) responses of the cone system to a flickering stimulus can exhibit a cyclic variation in amplitude. This phenomenon of synchronous period doubling has been attributed to a nonlinear feedback mechanism within the retina that alters response gain. The aim of the present study was to investigate intersubject variability in period doubling in the ERG of the human cone system, and to assess the implications of this variability for signal processing within the retina. Period doubling was examined in a group of 12 visually normal subjects, using sinusoidal full-field flicker and harmonic analysis of the ERG waveforms. For all subjects, the ERG responses to 32-Hz flicker (a frequency commonly used clinically) were characterized by a harmonic component at the stimulus frequency and at higher harmonics that were integral multiples of the stimulus frequency, as expected. In addition, six of the subjects showed period doubling at 32 Hz, characterized by harmonic components at integer multiples of a frequency that was half the stimulus frequency (the subharmonic). However, the subharmonic itself did not exceed the noise level. These findings suggest that the subharmonic is generated prior to or at the site that produces the nonlinear higher harmonics of the ERG response, and that a subsequent band-pass filter attenuates this subharmonic. Examination of harmonic components of the subjects' ERG waveforms at other stimulus frequencies, as well as a cycle-by-cycle analysis of the ERG waveforms, suggested that individual differences in period doubling may be due to intersubject variation in the strength of the hypothesized feedback signal and/or the time constant of its decay.