We have investigated by immunofluorescence the appearance of immunoreactive guanosine 3′-5′ cyclic monophosphate phosphodiesterase (cGMP-PDE) during the postnatal development of the retina of the pigmented rat. We show that a sudden increase in immunoreactivity takes place during postnatal day five (P5), when rod outer segments begin to form; immunoreactivity develops rapidly in the following days. Labeling is restricted to the developing photoreceptor outer segments, sparing other retinal cells, as confirmed by electron microscopy immunocytochemistry. In addition, cGMP-PDE immunoreactivity follows a center-to-periphery gradient paralleling photoreceptor differentiation. It appears that cGMP-PDE is expressed when the photoreceptor subcellular compartments are already formed, and represents a specific marker of late photoreceptor differentiation. The appearance of cGMP-PDE during development is temporally correlated with the appearance of other proteins of the phototransduction machinery.

The lateral geniculate nucleus (LGN) of every primate examined contains a set of small relay cells in addition to separate sets of magnocellular and parvocellular relay cells. These small cells receive a direct retinal projection, and an indirect retinal projection via the superior colliculus (SC). Receptive-field analyses of the small LGN cells in the bush baby, a lorisiform primate, indicate that this cell class is composed of subclasses, similar in physiology to cat W cells. In an effort to identify some of these subclasses, we have examined the morphological features of retinal and collicular axonal arbors that end on small W-like cells in the LGN of the bush baby, Galago crassicaudatus. Small cells in this species are found in a prominent pair of koniocellular (K) layers as well as the interlaminar zones (ILZs).

Retinal arbors were examined by bulk iontophoretic injection of horseradish peroxidase into the optic tract. Collicular arbors were filled via iontophoretic injection of biocytin into the superficial layers of the SC. Forty-eight axon arbors were completely reconstructed and quantitatively evaluated. Our findings show that retinal and collicular axon terminals differ in morphology on the basis of a number of criteria. Our analyses also suggest that retinal axons may have a stronger influence on K cells and collicular axons have a stronger influence on ILZ cells. The ramifications of these findings are provocative since these small LGN cells are known to project directly to the cytochrome-oxidase (CO) blobs within striate cortex. This relationship suggests that CO blob cells receive complex visual input not only from magnocellular and parvocellular LGN cells, but also from small cell pathways that are differentially influenced by retinal and collicular cells.

Recordings of field potentials in nucleus isthmi (NI) were obtained in an in vitro preparation of goldfish brain using a lateral approach. Horseradish peroxidase (HRP) was injected from recording electrodes to verify recordings within the nucleus and to label axonal pathways and cell bodies. Activity in NI was repetitive and could be elicited by stimulation of the optic nerve, tectum, pretectum, or tectobulbar tract. Spontaneous activity was present in some preparations and consisted of bursts with intervening silent periods. Anatomical and electrophysiological evidence indicated that the primary isthmotectal pathway is composed of fine fibers that exit NI rostrally and pass through pretectum to enter tectum rostrally. An afferent pathway consisting of both fine- and large-diameter fibers entered NI ventromedially; the large diameter axons have been previously reported in percomorph fishes, but were not thought to be present in cyprinids such as goldfish. The large diameter axons arise from labeled cell bodies in the region of the lateral thalamic nucleus. No labeled cell bodies were seen in ipsilateral nucleus pretectalis superficialis, pars magnocellularis, where they are seen in percomorphs. The fine axons, which have not been reported in percomorph fishes, were shown to arise from tectal bipolar (type VI) neurons. As in percomorphs, tectal type XIV neurons were also labeled. This and corroborating recordings from nucleus isthmi constitute the first demonstration of a tectoisthmic projection in a cyprinid fish.

Visually evoked field potentials in human subjects and single-cell responses from retinal ganglion cells in the macaque monkey were compared in closely similar stimulus situations. The classical heterochromatic flicker photometry (HFP) technique was used to measure spectral sensitivity in man, both psychophysically and by recording the 40-Hz response, and to measure the spectral sensitivity of magnocellular (MC-) pathway cells of the macaque. The three measures gave closely similar spectral-sensitivity curves. Close agreement between the three measures was also found when the variable-modulation HFP technique was used to measure spectral sensitivity. When the relative phase between red and green lights was varied, the point of minimum subjective flicker for human observers was close to a sharp minimum found in the amplitude of the 40-Hz response in human and was also close to a minimum in the response of MC-pathway neurons in the monkey. The human 40-Hz response saturated at between 10 and 30% modulation depth, and so did the response of MC-pathway cells in the monkey.

The 16-Hz response in human showed none of the above correlations with MC-pathway properties. On the other hand, parvocellular (PC-) pathway cells responded vigorously to constant-luminance, chromatic modulation, at frequencies higher than can be detected by human observers. The human 16-Hz response also was strong in that stimulus situation. In addition, the response of PC-pathway cells on increasing modulation depth showed little saturation, and this behaviour was paralleled by the human 16-Hz response.

We conclude that the properties of MC-pathway neurons in macaque are closely similar to the properties of the human 40-Hz response in the respects just described. We suggest that the 40-Hz response may offer a means of objectively isolating and investigating the contribution of the magnocellular stream to cortical activity in human. In contrast, the properties of PC-pathway neurons in macaque are quite different from the properties of the human 40-Hz response, and in several respects resemble the properties of the human 16-Hz response.

Studies of form-deprivation myopia (FDM) in animal models have shown that postnatal ocular growth is regulated by the quality of patterned images on the retina. One of the major challenges in myopia research is to identify the biochemical mechanisms which translate retinal visual responses into signals that regulate scleral growth. Dopamine (DA) has been implicated in this process, since retinal DA levels decline in FDM and subconjunctival injections of apomorphine (Apo, a nonspecific DA agonist) prevent FDM in a dose-dependent way (Stone et al., 1989).

To gain insight into where and how DA ligands act to regulate ocular elongation, we compared the action and distribution of DA receptor ligands injected intravitreally vs. subconjunctivally in young chicks. Ocular length was measured by A-scan ultrasound. We found that daily intravitreal injections of Apo block FDM at a 50% effective dose (ED50) of 5 pg per day, or a peak concentration in the vitreous humor of 108 pM, compared to an ED50 of 2.5 ng for subconjunctival injections as reported by Stone et al. (1989, 1990). [3H]-spiperone, a D2-receptor antagonist, reached average maximum retinal concentrations of 160 pM and 260 pM, during the first hour after intravitreal and subconjunctival administration, respectively, at the ED50 dose. In contrast, the maximum spiperone concentrations in the retinal pigment epithelium (RPE) were 30 pM and 410 pM, respectively, after intravitreal or subconjunctival ED50 doses. Spiperone concentrations in sclera after ED50 doses to the two sites differed by 4 x 104 (0.4 pM vs. 1.7 nM, respectively). The FDM-preventing action of Apo was blocked completely by simultaneous administration of spiperone but not by SCH 23390 (a D1-receptor antagonist) in 100-fold molar excess.

These results show that apomorphine acts to prevent FDM at an intraocular site, presumably in retina and/or pigment epithelium, but not sclera, whether administered intravitreally or subconjunctivally. A dose yielding a concentration of 100–260 pM, delivered ≤1 h per day, produces half-maximal inhibition. This action is mediated by D2-receptors, for which the dissociation constant for apomorphine is ≤1 nM. The retinal pigment epithelium may act as a trophic relay station, responding to a retinal messenger which may be DA and secreting scleral growth-regulator(s) from its basal surface.

Although serotonin is thought to be a neurotransmitter in a number of retinal systems, much of the precise synaptic connectivity of serotonergic neurons is unknown. To address this issue, we used an antiserum directed against serotonin to label serotonergic bipolar and amacrine cells in the turtle retina. Light-microscopic analysis of labeled amacrine and bipolar cells indicated that both had bistratified dendritic arborizations primarily in stratum 1 and in strata 4/5 of the inner plexiform layer.

Ultrastructural analysis of the neurocircuitry of these cells indicated that the processes of labeled bipolar cells in the outer plexiform layer made basal junction contacts with photoreceptor terminals. Only in rare instances did labeled bipolar cells processes invaginate near photoreceptor ribbon synapses. Processes of labeled bipolar cells received both conventional and small ribbon synaptic contacts in the outer plexiform layer. Bipolar cell processes in stratum 1 of the inner plexiform layer synapsed onto either amacrine/amacrine or amacrine/ganglion cell dyads, and made rare ribbon synaptic contacts onto labeled amacrine cell processes. Synaptic inputs to serotonergic bipolar cells in stratum 1 were from unlabeled bipolar and amacrine cells. Bipolar cell contacts in strata 4/5 were similar to those in stratum 1, but were fewer in number and no bipolar cell inputs were seen.

Labeled amacrine cell output in both strata was onto other unlabeled amacrine cells and ganglion cells; but synaptic outputs to unlabeled bipolar cells were only seen in strata 4/5. In both strata 1 and 4/5, synaptic inputs to labeled amacrine cells were from both unlabeled amacrine cells and labeled bipolar cells. The serotonergic amacrine cells had many more synaptic interactions in stratum 1 than in strata 4/5 which supports the role of serotonergic bipolar cells in the OFF pathway of retinal processing. Interactions between serotonergic bipolar and amacrine cells may play an important role in visual processing.

Synaptic transmission from photoreceptors to depolarizing bipolar cells is mediated by the APB glutamate receptor. This receptor apparently is coupled to a G-protein which activates cGMP-phosphodiesterase to modulate cGMP levels and thus a cGMP-gated cation channel. We attempted to localize this system immunocytochemically using antibodies to various components of the rod phototransduction cascade, including Gt (transducin), phosphodiesterase, the cGMP-gated channel, and arrestin. All of these antibodies reacted strongly with rods, but none reacted with bipolar cells. Antibodies to a different G-protein, Go, reacted strongly with rod bipolar cells of three mammalian species (which are depolarizing and APB-sensitive). Also stained were subpopulations of cone bipolar cells but not the major depolarizing type in cat (b1). Go antibody also stained certain salamander bipolar cells. Thus, across a wide range of species, Go is present in retinal bipolar cells, and at least some of these are depolarizing and APB-sensitive.

To provide a quantitative description of postnatal retinal expansion in rabbits, a new procedure was developed to map the retinae, which cover the inner surface of hemispheres or parts of rotation ellipsoids, in situ, onto a single plane. This method, as well as the known distribution of Müller cells per unit retinal surface area, were used to estimate the redistribution of specific subpopulations of Müller cells within different topographic regions of the retinae. Müller cells are known to exist as a stable population of cells 1 week after birth and can therefore be used as “markers” for determining tissue expansion. Our results show that differential retinal expansion occurs during development. Peripheral retinal regions expand at least twice as much as the central ones. Furthermore, there is a greater vertical than horizontal expansion. This differential retinal expansion leads to a corresponding redistribution of 5-hydroxytryptamine (5-HT) accumulating amacrine cells. Differential retinal expansion, however, does not account for all of the changes in the centro-peripheral density gradient of cells in the ganglion cell layer (GCL) — mostly retinal ganglion cells — during postnatal development. The changes in the ganglion cell layer were evaluated in Nissl-stained wholemount retinal preparations. Additionally, the difference between expansion-related redistribution of cells in the GCL and Müller cells was confirmed in wholemount preparations where Müller cells (identified as vimentin positive) and cells in the GCL (identified by fluorescent supravital dyes) were simultaneously labeled. It is assumed that many of the ganglion cells within the retinal center are not translocated during retinal expansion, possibly because their axons are fixed. In contrast, 5-HT accumulating amacrine cells — which are interneurons without a retinofugal axon — display a passive redistribution together with the surrounding retinal tissue.

Receptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area-threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-thresholdcurves. Altlhough the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits.

We investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direction channel.

In a dichromatic teleost species, we determined the intensity of light of various wavelengths required to prevent cone elongation by exposing fish at the time of their normal “dusk” phase to monochromatic light (479, 623, and 660 nm) at eight to ten different intensities for 75 min. The positions of single and double cones were measured in tangential sections and expressed as cone indices. At all wavelengths, the spectral responses of both cone types were virtually identical. Furthermore, the sensitivity of the blocking effect was highest at shorter wavelengths. When comparing the relative quantal sensitivities of myoid elongation for the two cone types to the spectral sensitivities of the three types of Aequidens pulcher photoreceptor, we found the closest match between the action spectrum and the absorption spectrum of the green-sensitive single cones. This may indicate that this cone type is capable of reacting directly to decreasing levels of illumination. On the other hand, the identical sensitivity of both cone types argues for an indirect control mechanism of dark-adaptive cone elongation, possibly via a neural pathway involving the inner retinal layers, complementary to the neural control of light adaptation. Green-sensitive single cones are well suited to trigger this response, since (1) their sensitivity is inferior to that of double cones; (2) waters inhabited by the blue acara transmit best at long wavelengths; and (3) at dusk, long-wavelength radiation dominates over other parts of the spectrum. Therefore, green-sensitive cone threshold will be reached first at dusk.

The role of dopamine as the endogenous signal-initiating light-dependent changes in the distribution of pigment granules in goldfish retinal pigment epithelium was investigated. In normal retinas, light adaptation resulted in the dispersion of pigment granules. This effect of light was mimicked by the intraocular injection of dopamine or serotonin, which is thought to increase endogenous dopamine release, into dark-adapted eyes. The effect of light, dopamine, or serotonin on dark-adapted retinas was blocked by the dopamine receptor antagonists haloperidol and sulpiride. However, lesioning the endogenous source of retinal dopamine, by prior intraocular injection of 6-hydroxydopamine (6-OHDA), did not block the dispersion of pigment granules in light-adapted retinas. No significant differences in pigment dispersion were noted between unlesioned and lesioned light- or dark-adapted retinas. However, the effect of light on pigment dispersion was no longer blocked by haloperidol or sulpiride in 6-OHDA lesioned animals. Dopamine and serotonin mimicked the effect of light when injected into lesioned dark-adapted eyes, but their effects were also not blocked by haloperidol or sulpiride. These results suggest that dopamine, acting on D2 receptors, is sufficient to induce pigment migration in unlesioned animals. In 6-OHDA-lesioned animals, however, pigment migration is mediated by a receptor mechanism other than D2.

Interocular alignment was assessed by corneal light reflex photography in 15 normal and 26 strabismic kittens. Strabismus was induced at 3–4 weeks of age by severing one extraocular muscle (tenotomy), by cutting and reinserting the muscle at another position on the ocular globe (recession), or by combining recession of the medial rectus muscle with resection of the lateral rectus muscle of the same eye. Nineteen strabismic and five normal kittens were followed longitudinally from 12 days to about 6 months of age.

Three out of the six longitudinally followed tenotomized cats and six out of the 13 recessed cats conserved their postoperative ocular deviation throughout the testing period (“large-angle strabismics”). Three tenotomized and seven recessed cats showed a transient deviation for 1–2 weeks after surgery, after which the interocular deviation diminished to values found in normal cats (“microstrabismic” cats). Both recessed-resected cats showed a transient interocular deviation.

In spite of their different developmental histories, all cats showed a clear breakdown of binocularity in area 17. Large-angle strabismics showed a dominance of the non-operated eye, while in microstrabismic cats, both eyes were equally effective in driving cortical cells. It thus appears that a transient strabismus is sufficient to produce a reduction of binocularity in area 17.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. The present paper describes the localization of GABAA receptors in the rat retina as revealed by in situ hybridization and immunocytochemistry.

In situ hybridization with probes against various a subunits revealed a marked differential expression pattern. The αl subunit gene is expressed mainly in the bipolar and horizontal cell layer, the α2 gene in the amacrine and ganglion cell layer, and the α4 gene in a subpopulation of amacrine cells. β subunit mRNA is present diffusely throughout the entire inner nuclear layer and in the ganglion cell layer.

The monoclonal antibody bd 17 (against β2/β3 subunits) stained subpopulations of GABAergic and glycinergic amacrine cells as well as some ganglion cells and bipolar cells. Immunoreactivity was not restricted to synaptic input sites. In the outer plexiform layer bipolar cell dendrites were immunoreactive; in the inner plexiform layer mainly amacrine and ganglion cell processes were labeled, and bipolar cell axons appeared unstained. The results demonstrate a strong heterogeneity of GABAA receptors in the retina.

On the basis of cortical connections and architectonics, inferior temporal (IT) cortex of squirrel monkeys consists of a caudal, prestriate-recipient region, ITC; a rostral region, ITR; and possibly an intermediate region along the border of ITC and ITR, ITI (Weller & Steele, 1992). ITC contains dorsal (ITCd) and ventral (ITCv) areas. The subcortical connections of these subdivisions of IT cortex were determined in the present study from the results of cortical injections of wheat-germ agglutinin conjugated to horseradish peroxidase, [3H]-amino acids and fast blue. ITC and ITR receive afferents from the locus coeruleus, dorsal raphe, nucleus annularis, central superior nucleus, pontine reticular formation, lateral hypothalamus, paracentral nucleus, and central medial nucleus; send efferents to the superior colliculus, reticular nucleus, and striatum; and have both afferent and efferent connections with the pretectum, pulvinar, claustrum, amygdala, and basal nucleus of Meynert. ITC and ITR have different patterns of connections with a number of subcortical structures, including the pulvinar and amygdala. Injections in ITC strongly label multiple nuclei of the inferior pulvinar and the medial division of the lateral pulvinar (PLM), and moderately label the medial pulvinar (PM), whereas injections in ITR strongly label PM and moderately label PLM. Injections in ITC label sparse projections to the lateral nucleus of the amygdala, in contrast to injections in ITR that label strong projections to the lateral and basal nuclei of the amygdala. Injections in “IT” produce a pattern of subcortical label that has some features of that observed from injections in ITC and that observed from injections in ITR. Although most of the connections of ITCd and ITCv appear similar, only injections involving ITCd label the middle nucleus of the inferior pulvinar (PIM).

Comparison of the subcortical connections of subdivisions of IT cortex in squirrel monkeys and what is presently known of the subcortical connections of subdivisions of IT cortex in macaque monkeys supports the previous suggestion that ITC of squirrel monkeys may be comparable to area TEO of macaques, IT, may be comparable to posterior area TE, and ITR may be comparable to anterior area TE (Weller & Steele, 1992).