To gain insight into how vision guides eye movements, monkeys were trained to make a single saccade to a specified target stimulus during feature and conjunction search with stimuli discriminated by color and shape. Monkeys performed both tasks at levels well above chance. The latencies of saccades to the target in conjunction search exhibited shallow positive slopes as a function of set size, comparable to slopes of reaction time of humans during target present/absent judgments, but significantly different than the slopes in feature search. Properties of the selection process were revealed by the occasional saccades to distractors. During feature search, errant saccades were directed more often to a distractor near the target than to a distractor at any other location. In contrast, during conjunction search, saccades to distractors were guided more by similarity than proximity to the target; monkeys were significantly more likely to shift gaze to a distractor that had one of the target features than to a distractor that had none. Overall, color and shape information were used to similar degrees in the search for the conjunction target. However, in single sessions we observed an increased tendency of saccades to a distractor that had been the target in the previous experimental session. The establishment of this tendency across sessions at least a day apart and its persistence throughout a session distinguish this phenomenon from the short-term (<10 trials) perceptual priming observed in this and earlier studies using feature visual search. Our findings support the hypothesis that the target in at least some conjunction visual searches can be detected efficiently based on visual similarity, most likely through parallel processing of the individual features that define the stimuli. These observations guide the interpretation of neurophysiological data and constrain the development of computational models.

Excitatory amino acid (EAA)-induced production of inositolphosphates (IPs) was studied in primary cultures of chick retinal pigment epithelium (RPE) following in vitro incorporation of [3H] myo-inositol. Glutamic acid (L-glu) significantly increased [3H]-IPs accumulation (215%). L-glu agonists stimulated [3H]IPs accumulation in the following order of efficiency: N-methyl-D-aspartate (NMDA) ≥ L-glu > quisqualate ≥ kainate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD). Stimulation was dependent on external Ca2+. The NMDA-induced response was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo-cyclohepten-5,10-imine maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and was decreased by the L-Ca2+-channel blockers verapamil and nifedipine as well as by dantrolene. The metabotropic glutamate receptor (mGluR) antagonist (+)-α-methyl-4-carboxyphenylglycine (+)MCPG inhibited 3,5-dihydroxyphenylglycine (DHPG) and ACPD-induced stimulation, which demonstrates the presence in RPE of mGluRs 1 and/or 5, as well as NMDA receptors coupled directly, or through the influx of external Ca2+, to phospholipase C activation. L-glu agonists showed no effect either on basal level of intracellular cyclic adenosine monophosphate, nor on forskolin- or carbachol-induced stimulation of adenylyl cyclase. Since L-glu is released from the retina upon illumination, and receptors for this compound are present in RPE, the activation of the inositide pathway could be involved in the regulation of retina-RPE interaction, which is essential for the visual process.

Light-microscopic immunocytochemistry was utilized to localize the different populations of substance P-immunoreactive (SP-IR) neurons in the hamster retina. Based on observation of 2505 SP-IR neurons in transverse sections, 34% were amacrine cells whose pear-shaped or round cell bodies (7–8 μm) were situated in the inner half of the inner nuclear layer (INL) or in the inner plexiform layer (IPL), while 66% of SP-IR somata (6–20 μm) were located in the ganglion cell layer (GCL) which were interpreted to be displaced amacrine cells and retinal ganglion cells (RGCs). At least three types of SP-IR amacrine cells were identified. The SP-IR processes were distributed in strata 1, 3, and 5 with the densest plexus in stratum 5 of the inner plexiform layer. In the wholemounted retina, the SP-IR cells were found to be distributed throughout the entire retina and their mean number was estimated to be 4224 ± 76. Two experiments were performed to clarify whether any of the SP-IR neurons in the GCL were RGCs. The first experiment demonstrated the presence of SP-IR RGCs by retrogradely labeling the RGCs and subsequently staining the SP-IR cells in the retina using immunocytochemistry. The second experiment identified SP-IR central projections of RGCs to the contralateral dorsal lateral geniculate nucleus. This projection disappeared following removal of the contralateral eye. The number of SP-IR RGCs was estimated following optic nerve section. At 2 months after sectioning the optic nerve, the total number of SP-IR neurons in the GCL reduced from 4224 ± 76 to a mean of 1192 ± 139. Assuming that all SP-IR neurons in the GCL which disappeared after nerve section were RGCs, the number of SP-IR RGCs was estimated to be 3032, representing 3–4% of the total RGCs. In summary, findings of the present study provide evidence for the existence of SP-IR RGCs in the hamster retina.

In the lizard, Ctenophorus ornatus, anatomical studies have revealed that optic axons regenerate to visual centers within 2 months of nerve crush but that, from the outset, the regenerated projections lack topographic order (Beazley et al., 1997; Dunlop et al., 1997b). Here we assess the functional topography of the regenerated retinotectal projections by electrophysiological recording of extracellular multiunit responses to visual stimulation and by observing the lizards' ability to capture live prey. At the completion of the electrophysiology, DiI was applied locally to the retina and the topography of the tectal projection later assessed. Electrophysiology revealed that, at 2–4.2 months, responses were weak and habituated readily; no retinotopic order was detected. Between 4.5–6 months, responses were more reliable and the majority of lizards displayed a crude retinotopic order, especially in the ventro-temporal to dorso-nasal retinal axis. Although responses were variable between 6–9 months, they tended to be more reliable again thereafter. However, from 6–18 months, the projection consistently lacked topography with many retinal regions projecting to each tectal locus. Lizards, including those with electrophysiological evidence of crude retinotopy, were consistently unable to capture live prey using the experimental eye. Labelling with DiI confirmed the absence of anatomical retinotopy throughout. Taken together, the electrophysiological and anatomical data indicate that retinotopically appropriate axon terminals (or parts thereof) are transiently active whilst inappropriately located ones are silent. Presumably in lizard map-making cues fade with time and/or the mechanisms are lacking to stabilize and refine the ephemeral map. Moreover, the transient retinotopy is insufficient for useful visual function.

We studied the off-response of the rat ERG evoked with long duration, mesopic stimuli during light and dark adaptation, and after intravitreal injection of aspartate and (±)-cis-piperidine-2,3-dicarboxilic acid (PDA). At stimulus offset, the dark-adapted ERG always showed a rapid negative deflection followed by a positive deflection after which the potential returned to baseline. When the stimulus was turned off in the presence of a background of scotopic intensity, the positive deflection consisted of two components. One component was relatively small, fast, and insensitive to rod light adaptation. It resembled the d-wave of the rod ERG. The other component was slow and its amplitude grew with rod light adaptation. In the presence of aspartate, the fast-positive component was absent from the ERG while the remaining positive-going decay of the receptor potential had a time course similar to that of the slow-positive component in the untreated eye. Scotopically matched red and blue stimuli of mesopic intensity elicited equal ERG responses from the dark-adapted eye, including the two positive components in the off-response. These stimuli were also used to assess changes in the ERG off-response during recovery from a strong bleach. Even though the cone contribution to the rat ERG is very small, the presence of a small positive-going component in the off-response following an intense bleach suggested that this response originated from the cone pathway. PDA which suppresses the light response of hyperpolarizing bipolar cells and horizontal cells selectively eliminated the fast-positive component from the ERG. The findings of this study are inconsistent with the idea that the d-wave reflects the decay of the rod receptor potential. They support the possibility that signals from rods cross rod–cone gap junctions at mesopic light intensities, and drive second-order neurons in the cone pathway.

Immunohistochemistry for choline acetyltransferase (ChAT) revealed an extensive network of cholinergic fibers in the tectum of amphibians. The distribution of ChAT immunoreactive fibers was not restricted to superficial retinocipient layers, but also included deep tectal layers. The aim of the present study was to investigate the origin of the cholinergic inputs to the tectum of amphibians. For that purpose, application of retrograde tracers in the tectum of the anuran Rana perezi and the urodele Pleurodeles waltl was combined with ChAT immunohistochemistry. Double-labeled cells were found primarily in the nucleus isthmi of both species. The cholinergic isthmotectal projection is bilateral and topographically arranged and all retrogradely labeled cells found in this nucleus were ChAT immunoreactive. Remarkably, abundant cholinergic cells in two tegmental nuclei, the pedunculopontine tegmental nucleus (anurans) and the laterodorsal tegmental nucleus (anurans and urodeles), were demonstrated to provide additional cholinergic innervation to the tectum. We compare the present results with previously reported studies in amphibians and other vertebrates, and discuss the possible functional significance of the cholinergic innervation of the amphibian tectum.

Extensive evidence has suggested a trophic role of γ-aminobutyric acid (GABA) on developing cone photoreceptors in postnatal retina. In a previous study, we showed that GABA raises intracellular calcium levels in the developing cones via activation of GABAA receptors. Using confocal microscopy in conjunction with immunocytochemistry, we have now demonstrated that (1) GABAA receptor subunits are localized on cone cell bodies as well as on cone pedicles, indicating that GABA has a direct, rather than indirect, effect on cones and (2) the temporal expression of GABAA receptor subunits coincides with the developmental effects of GABA on cone synaptogenesis. An antibody against the β 2/3 subunits of the GABAA receptor and a specific cone marker peanut-agglutinin lectin (PNA) were used to double-label wholemount neonatal retinal preparations. Results show that GABAA receptors are transiently expressed on cone photoreceptors in the early stages of postnatal retinal development. GABAA receptor immunoreactivity is clearly present on cone cell bodies and their processes and on other—as yet unidentified—elements (horizontal cells?) in the outer plexiform layer. Immunoreactivity decreases within cone photoreceptor somata after postnatal day 5, but persists in the processes of the outer plexiform layer until day 7. Our results provide support for the hypothesis that GABA acts as an important developmental regulator of cone photoreceptor maturation.

Research has shown that adult zebrafish have a complex visual system, with two possible opponent mechanisms. Anatomically, zebrafish retina develops in a sequential manner and is immature at hatching. The purpose of the present study was to assess zebrafish retinal development using the electroretinogram (ERG). ERG responses to visual stimuli were obtained from 4–5, 6–8, 13–15, and 21–24 days postfertilization (dpf) zebrafish. Individual waveforms were assessed and compared across the four age groups. Spectral-sensitivity functions were calculated for the a- and b-wave components of the ERG response. Results showed that the ERG waveforms and spectral-sensitivity functions varied with age. While the 21–24 dpf subjects had an ERG waveform that was similar to that of adults, the younger subjects did not. Although there were modest differences in the a-wave spectral sensitivity, substantial differences were found in the b-wave spectral sensitivities across the ages. There was a consistent strong response to ultraviolet wavelengths, while across the remaining parts of the spectrum, there was a gradual increase in sensitivity with age. Also, the 21–24 dpf subjects appear to have adult-like U- and S-cone functions, but were missing the L-M and the M-S opponent mechanisms found in the adult. These results support the findings of the anatomical studies and demonstrate that the zebrafish is a useful model for examining the development of retinal function.

Our objective with this study was to provide a near complete characterization of how mean light level changes the spatial receptive-field properties of X-cells. Single X-cells were recorded extracellularly either from cell bodies in the retina or from their axons in the optic tract. Frequency responses of the cells at 2 Hz were measured for a set of gratings of different spatial frequencies and for a stimulus designed to probe the spatial properties of the receptive-field surround. Predicted frequency responses of a Gaussian center-surround model for the receptive field were fit simultaneously to both sets of measurements and the parameters of the model that best fit the data used to characterize the spatial properties of the receptive field. Measurements were made at a number of mean light levels for each cell and changes in receptive-field properties were characterized by changes in the parameters of the Gaussian center-surround model. The range of illuminances studied covered the bulk of the range encountered by a cat naturally and three distinct functional ranges appeared to express themselves in the data. One range corresponded to the cat's photopic range of vision. The other two ranges were where signals originating in rods dominate X-cell responses. We argue that one corresponds to the range that rod signals pass predominantly through rod bipolars en route to the X-cell, while the other is where rod signals flow predominantly through cones via gap junctions and then follow the path of cone signals to the X-cell. Among the major findings are that Weber's Law is followed throughout the photopic but not the scotopic range, that center radius expands under scotopic conditions, and that the surround is present even at the lowest scotopic levels we studied.

The patterns of glutamate, γ-aminobutyric acid (GABA), and glycine distribution in the zebrafish retina were determined using immunocytochemical localization of antisera at the light-microscope level. The observed GABA immunoreactivity (GABA-IR) patterns were further characterized using antibodies to both isoforms of glutamic acid decarboxylase (GAD65 and GAD67), the synthetic enzyme for GABA. Glutamate-IR was observed in all retinal layers with photoreceptors, bipolar cells, and ganglion cells prominently labeled. Bipolar cells displayed the most intense glutamate-IR and bipolar cell axon terminals were clearly identified as puncta arranged in layers throughout the inner plexiform layer (IPL). These findings suggest the presence of multiple subtypes of presumed OFF- and ON-bipolar cells, including some ON-bipolar cells characterized by a single, large (9 μm × 6 μm) axon terminal. GABA-, GAD-, and glycine-IR were most intense in the inner retina. In general, the observed labeling patterns for GABA, GAD65, and GAD67 were similar. GABA- and GAD-IR were observed in a population of amacrine cells, a few cells in the ganglion cell layer, throughout the IPL, and in horizontal cells. In the IPL, both GABA- and GAD-IR structures were organized into two broad bands. Glycine-IR was observed in amacrine cells, interplexiform cells, and in both plexiform layers. Glycine-positive terminals were identified throughout the IPL, with a prominent band in sublamina 3 corresponding to an immunonegative region observed in sections stained for GAD and GABA. Our results show the distribution of neurons in the zebrafish retina that use glutamate, GABA, or glycine as their neurotransmitter. The observed distribution of neurotransmitters in the inner retina is consistent with previous studies of other vertebrates and suggests that the advantages of zebrafish for developmental studies may be exploited for retinal studies.

We analyzed postsynaptic potentials and dye-labeled morphology of tectal neurons responding to electrical stimulation of the optic nerve and of the nucleus isthmi in a reptile, Gekko gekko, in order to compare with previously reported interactions between the optic tectum and the nucleus isthmi in amphibians and birds. The results indicate that isthmic stimulation exerts inhibitory and excitatory actions on tectal cells, similar to dual isthmotectal actions in amphibians. It appears that dual actions of the isthmotectal pathway in amphibians and reptiles are shared by two subdivisions of the nucleus isthmi in birds. The morphology of tectal cells responding to isthmic stimulation is generally similar to that of tectoisthmic projecting neurons, but they differ particularly in that some tectoisthmic cells bear numerous varicosities whereas cells receiving isthmic afferents do not. Thus, it is likely that at least some tectoisthmic cells may not be in the population of tectal cells that can be affected by isthmic stimulation. Forty-four percent of injections resulted in dye-coupled labeling, suggesting extensive electrical connections between tectal cells in reptiles.

To determine the number of wide-field, monostratified ganglion cell classes present in the human retina, we analyzed a large sample of ganglion cells by intracellular staining in an in vitro, whole-mount preparation of the retina. Over 1000 cells were labeled by horseradish peroxidase or Neurobiotin; some 200 cells had wide dendritic trees narrowly or broadly stratified within either the inner (ON) or outer (OFF) portion of the inner plexiform layer. Based on dendritic-field size and the pattern and extent of dendritic branching, we have distinguished six wide-field cell groups. The giant very sparse ganglion cells included both inner and outer stratifying cells and were unique both for their extremely large dendritic field (mean diameter = 1077 μm) and extremely sparsely branched dendrites. Four of the cell groups had similarly large dendritic fields, ranging in mean diameter from 737 to 791 μm, but differed in the pattern and extent of dendritic branching, with the number of dendritic branch points ranging from a mean of 33 to 129. Of these four groups, the large very sparse group and the large dense group included both inner and outer stratifying cells, while the large sparse and large moderate groups consisted of inner stratifying cells only. The thorny monostratified ganglion cells were distinct from the other cells in having medium size dendritic fields (mean diameter = 517 μm) and moderately branched, inner stratifying dendritic trees with many thin, spiny, twig-like branchlets. All six groups had medium-size cell bodies, with mean soma diameters ranging from 17 to 21 μm. Though the physiological properties and central projections of human wide-field, monostratified ganglion cells are not known, some of the cells resemble macaque ganglion cells known to project to the lateral geniculate nucleus, the pretectum, or the superior colliculus.

Patch-clamp recordings were made from ganglion cells in an in vitro dark-adapted rabbit retina preparation. Cells were stimulated by images generated on a computer monitor and focussed onto the photoreceptors. Excitatory inward currents were recorded in response to spot stimuli centered on the somas of the recorded cells. Center illumination of on-brisk-transient cells produced large transient excitatory postsynaptic currents (EPSCs) which were invariably followed by a small steady-state inward component. Illumination of a centered annulus failed to elicit the transient EPSC. Simultaneous illumination of the annulus and the center spot blocked the large transient EPSC, consistent with activation of an inhibitory surround. Application of tetrodotoxin (TTX), which blocks sodium-dependent action potentials, also blocked the surround inhibition in ON-brisk transient cells as well as some other classes of ganglion cells. It is concluded that, in some ganglion cell classes, the surround is generated largely through the activity of spiking neurons, and it is suggested that the amacrine cells in the inner plexiform layer are involved.

Activity-dependent synaptic plasticity is characteristic of developing visual systems. Using the frog retinotectal system, we investigated the extent to which afferent input affects neurotransmitter expression in a target structure. We have concentrated on a particular subpopulation of tectal cells that is immunoreactive to substance P (SP). Early in development, SP expression in tectal neurons was restricted to the anterior lateral region of the tectum. As tadpoles developed, this expression expanded into progressively more posterior and medial regions in a manner that closely followed the gradient of tectal maturation. At all times, however, anterior and lateral tectal regions had a greater percent of SP-like immunoreactive (SP-ir) cells than posterior and medial ones. Horseradish peroxidase (HRP) labeling of the retinal ganglion cell projection in conjunction with SP immunocytochemistry demonstrated that innervation by retinal ganglion cell terminals preceded the expression of SP by tectal cells. This suggested that the optic nerve may influence SP differentiation and/or expression. In support of this idea, transection of the optic nerve resulted in a decrease in SP expression in the deafferented tectal lobe of tadpoles. This result, opposite to that seen previously in the adult, also indicates that optic nerve–dependent regulation of SP expression in the developing and mature systems occurs through different pathways.

Two types of cone bipolar cells, the blue cone bipolar cell and the diffuse bipolar cell (DB3), were labelled immunohistochemically and investigated in the retina of a New World monkey, the marmoset. Blue cone bipolar cells were labelled with an antiserum against cholecystokinin. Short-wavelength-sensitive (SWS) cones were labelled with an antiserum against the SWS cone opsin. The DB3 cells were labelled with antibodies to calbindin. Blue cone bipolar cells in marmoset do not form a regular mosaic but instead follow the random distribution of the SWS cones. Nevertheless, the SWS cone to blue cone bipolar cell connectivity in marmoset is very similar to that previously described for macaque. In contrast to the blue cone bipolar cells, the DB3 cells form a regular mosaic. The synaptic connectivity of DB3 cells in the inner plexiform layer was analyzed. They make output synapses onto ganglion cells and amacrine cells, and gap junctions with each other. Our results provide further evidence for the existence of parallel bipolar cell pathways in the primate retina and support the view that the retinae of Old World and New World primates have common neuronal connectivity. The random distribution of SWS cones and blue cone bipolar cells is an exception to the general rule of a regular mosaic distribution of cell populations in the retina.

Mammalian retinae generally contain low numbers of short-wavelength-sensitive cones (S-cones) and higher numbers of middle- to long-wavelength-sensitive cones (M-cones). Some recent studies found topographic differences between the different photoreceptor types and in some instances between photoreceptors and ganglion cells. To investigate this question further, we constructed topographical maps of the different photoreceptors found in an Australian marsupial, the tammar wallaby. We used two polyclonal antibodies that have been shown to label S-cones (JH455) or M-cones (JH492) in a range of mammals. In the tammar wallaby, the antisera clearly distinguish two cone types. JH455 recognizes a small subset of cones (S-cones) with a density of less than 500 cells/mm2 in the ventral retina. Their density increases towards the dorsal retina to about 1600–2000 cells/mm2. JH492 recognizes all remaining cones (M-cones), but also faintly labels most cone cells recognized by JH455. The distribution of M-cones, unlike that of the S-cones, shows a clear horizontal streak of high cell density through the central retina, just like the ganglion cells. Unlike the ganglion cells, however, the M-cones do not peak in the temporal retina but show a very broad peak (12,000–18,000 cells/mm2) in the central or even slightly nasal retina. Based on our findings, the retina of the tammar can be divided into three distinct regions: firstly, the dorsal retina, which has a low ganglion and low cone cell density but a high percentage of S-cones (30%), is thought to provide good spectral sensitivity; secondly, the central horizontal band of retina, which has a high ganglion and high cone cell density and therefore provides good spatial resolution; and thirdly, the ventral retina, which has a low ganglion cell but high cone cell density with few S-cones (5%) and is therefore thought to have a high contrast sensitivity but low acuity.

AMPA-selective glutamate receptors play a major role in glutamatergic neurotransmission in the retina and are expressed in a variety of neuronal subpopulations. In the present study, immunocytochemical techniques were used to visualize the distribution of GluR2 and GluR4 subunits in the cat retina. Results were compared with previous localizations of GluR1 and GluR2/3. Staining for GluR2 was limited to a small number of amacrine and ganglion cells whereas GluR4 staining was present in A-type horizontal cells, many amacrine cells including type AII amacrine cells, and the majority of the cells in the ganglion cell layer. Analysis of synaptic relationships in the outer plexiform layer showed the GluR4 subunit to be concentrated at the contacts of cone photoreceptors with A-horizontal cells. In the inner plexiform layer, both GluR2 and GluR4 were postsynaptic to cone bipolar cells at dyad contacts although GluR2 staining was limited to one of the postsynaptic elements whereas GluR4 immunoreactivity was often seen in both postsynaptic elements. Unlike GluR2, GluR4 was also postsynaptic to rod bipolar cells where it could be visualized in processes of AII amacrine cells. The data indicate that GluR3 and GluR4 subunits are colocalized in a number of cell types including A-type horizontal cells, AII amacrine cells, and alpha ganglion cells, but whether they are combined in the same multimeric receptors remains to be determined.

Local electroretinograms (ERGs) were recorded in the parietal eye of Xantusia vigilis. The responses to monochromatic light under dark- and light-adapted conditions were studied. We found that two antagonistic chromatic mechanisms dominate the overall response. With the electrode tip in the lumen of the eye, light stimulation under dark-adapted conditions evoked responses of negative polarity with maximum sensitivity to green light. Intense green background illumination saturated the green-sensitive mechanism, and superposition of a blue stimulus then elicited responses of opposite polarity, driving the potentials back toward the dark resting level. The spectral sensitivities of the two chromatic mechanisms were determined using chromatic adaptation. The lower threshold, green-sensitive mechanism has a maximum sensitivity at 495 nm while the antagonistic mechanism, with its maximal spectral sensitivity at 430 nm, is at least 2 log units less sensitive. The polarity of the ERG recording inverts as the electrode traverses the photoreceptor layer, suggesting that the photoreceptors are the major source of the ERG. This result was confirmed with intracellular recordings from photoreceptors, glial, and lens cells. The glial and lens cells of the parietal eye respond to local changes in [K+]o. Intracellular recordings of the responses of these cells to light stimuli follow time courses similar to changes in extracellular potassium concentrations measured with K+-specific electrodes. These results suggest that the glial and lens cell membranes are highly permeable to potassium and, therefore, the electrical responses of these cells are evoked by changes in [K+]o elicited by light stimulation of the photoreceptors. Nevertheless, the major component of the parietal eye ERG is the photoreceptor signal. A circuit model of the ERG sources is presented.

Administration of a single subcutaneous dose of 5,7-dihydroxytryptamine (5,7-DHT) to newborn hamsters results in a significant increase in the density of serotoninergic (5-HT) fibers in the superficial layers of the superior colliculus (SC) and marked abnormalities in the uncrossed retinotectal projection when these animals reach adulthood (Rhoades et al., 1993). The present study was undertaken to determine whether elevation of 5-HT in the developing SC altered the visual representation in SC. Multi-unit recordings from SC cells demonstrated that the overall organization of the visual map in the superficial SC laminae was normal and that the receptive-field sizes for unit clusters were unchanged in the 5,7-DHT-treated animals. However, when a combination of CNQX and MK-801 was directly applied to the SC to block postsynaptic activity, the receptive fields of unit clusters (presumably retinotectal axon terminals) in the 5,7-DHT treated animals were significantly larger than those in the normally reared hamsters. These results are consistent with the conclusions that elevation of 5-HT levels in the developing SC reduces the postnatal refinement of the crossed retinotectal axons, and that mechanisms operating within the SC may act to maintain normal sizes for the receptive fields of its constituent neurons.

During early mammalian development, inputs from the two retinas intermix within the lateral geniculate nucleus (LGN), then segregate during the first postnatal week into layers that receive input from a single retina. Functionally, the LGN also changes markedly during the first postnatal month; early geniculate responses to retinal input are mainly excitatory, then inhibitory circuits mature within the LGN. These remarkable changes in form and function of the retinogeniculate pathway occur at a time when patterned visual activity is not present, but retinal ganglion cells already manifest spontaneous action potential activity. To examine the role of early retinal activity in these critical developmental processes, we placed the slow release polymer Elvax embedded with tetrodotoxin (TTX) into the vitreous chamber of one or both eyes of neonatal ferrets. Animals receiving monocular injection of TTX had the other eye treated with Elvax containing control citrate buffer. Intraocular injection of horseradish peroxidase was made at the end of the period of TTX treatment to reveal the retinal terminals in the LGN. Chronic monocular or binocular blockade of retinal activity during the first postnatal week did not prevent eye-specific segregation, although it made the boundaries between layers less distinct. Retinal terminals ended preferentially in the appropriate layer, but a large number of terminals were also present in the inappropriate layer. Further segregation was achieved during the second postnatal week of activity blockade, when most retinal terminals ended preferentially in the appropriate geniculate layer and sharper layer boundaries were present. However, a small but significant number of terminals still extended into the inappropriate layer. Together, these findings indicate that monocular as well as binocular blockade of retinal activity resulted in some anomalous retinogeniculate projections and delayed eye-specific patterning, but segregation was largely intact at the end of the second postnatal week. We also report here that intraocular tetrodotoxin had a marked effect on the maturation of intrinsic geniculate circuits prior to eye opening. Whole-cell patch-clamp recordings in the LGN slice preparation revealed that activity blockade prevented the maturation of the slow, but not the fast, hyperpolarizing potential of LGN neurons during the first postnatal month and up to P38, the oldest age studied. In conclusion, these results indicate that spontaneous retinal activity modulates the time course of binocular segregation but does not alone account for the segregation of retinogeniculate terminals. However, early retinal activity plays an important role in developing the intrinsic circuitry of the LGN.