Interplexiform cells are centrifugal neurons in the retina carrying information from the inner to the outer plexiform layers. In teleost fish, interplexiform cells appear to release dopamine in the outer plexiform layer after prolonged darkness that modulates the receptive-field size and light responsiveness of horizontal cells (Mangel & Dowling, 1985; Yang et al., 1988a, b). It has been proposed that interplexiform cells may also release dopamine upon steady illumination because horizontal cells' receptive fields shrink in the light (Shigematsu & Yamada, 1988). Here, we report the shrinkage of the receptive fields of horizontal cells seen in the presence of background illumination is not blocked by dopamine antagonists, indicating that dopamine does not underlie the receptive-field size changes observed during steady illumination. Flickering light, however, does appear to stimulate the release of dopamine from the interplexiform cells, resulting in a marked reduction of horizontal cell receptive-field size. Taken together, experiments on horizontal cells indicate that dopamine is released from interplexiform cells in the teleost retina after prolonged darkness and during flickering light, but that dopamine release from interplexiform cells during steady retinal illumination is minimal.

The representation of the visual field in the callosal fiber recipient zone of area 17 and the adjacent area 17/18 transition zone was determined in the cat. The callosal fiber recipient zone was identified by anterograde transport of tritiated amino acids that had been injected into transcallosal sending zone of the opposite hemisphere. Application of autoradiographic procedures revealed that transcallosal projections are densest in the area 17/18 transition zone, and that their density in area 17 diminishes within 1–2 mm of the transition zone. Of 980 sites sampled in the visual-field mapping part of the study, 507 proved to be in the zone demarcated by transcallosally transported label. In this zone, both ipsilateral- and contralateral-field positions are represented, and the representation of the visual field at the different elevations is not equal. When ipsilateral-field positions are considered, the representation extends to about 4 deg close to the visual axis, and to 15–20 deg at elevations >±30 deg, the representation is approximately mirror-symmetric about the horizontal meridian, and the representation is concordant with that of the representation in the area 17 transcallosal sending zone of the opposite hemisphere.

In both anesthetized and behaving macaques, we examined the responses of neurons in the inferior temporal cortex (IT) to repeated presentation of a visual stimulus. In anesthetized animals, the responsiveness of IT neurons decreased with repeated stimulus presentation at interstimulus intervals (ISIs) of 2–12 s but not at 20 s. Responsiveness recovered after a 5-min period of no stimulus presentation. The response decrement was similar in anesthetized and awake animals at a 2-s ISI, but at a 6-s ISI, response decrement in the awake animal was much less.

Catecholaminergic (presumed dopaminergic) amacrine cells in the retinae of Beagle dogs (canis lupus f. familiaris) and wolves (canis lupus) were visualized with an antiserum against tyrosine hydroxylase (TH). In both species, TH immunoreactivity is found in a population of amacrine cells with large somata (about 14 μm diameter) and large, moderately branched dendritic trees. Somata are located in the proximal inner nuclear layer (normal amacrines) or in the ganglion cell layer (displaced amacrines). Most dendrites stratify in a narrow band in the inner plexiform layer close to the inner nuclear layer, where they form a dense plexus with the characteristic pattern of “dendritic rings.” The displaced cells have some of their dendrites in a proximal stratum of the inner plexiform layer. A few immunopositive processes are found in the outer plexiform layer (interplexiform processes).

In Beagle dogs, the cell density of catecholaminergic amacrines varies from less than 1/mm2 in far periphery to 40–55/mm2 in central retina (mean density 21/mm2). The proportion of displaced amacrines varies locally from 10 to 85% (overall proportion 41% in one retina). In the wolf, densities of catecholaminergic cells range between about 3/mm2 in peripheral and up to 35/mm2 in central retina. The proportion of displaced cells is somewhat lower than in dogs, varying between 11 and 31% across the retina.

The morphology and density distribution of canine catecholaminergic amacrines resemble that of other mammalian retinae. A marked difference, however, is the high percentage of displaced cells in both dog and wolf retina; it is the highest found in any mammal so far. The displaced and normal cells appear to be members of a single functional population. A comparison of the topographic distributions of catecholaminergic amacrines, rods, and ganglion cells in the dog retina shows no consistent density correlations between these neurons that are all part of the rod pathway.

Illumination greatly increases the GTPase activity in homogenates of squid (Loligo) whole retinas or rhabdomeric membranes. Adenylylimidodiphosphate inhibits the light-insensitive (but not the light-sensitive) GTPase activity in these homogenates. Illumination also greatly increases the binding of GTP[γS] to the rhabdomeric membranes. This binding at saturating illuminations indicates that there are approximately 10–100 times more rhodopsin molecules than G-protein molecules in squid photoreceptors. Each light-activated rhodopsin molecule activates about 10 G-protein molecules which might provide amplification for the first stage of the phototransduction cascade.

The distribution of honeybee retinal photoisomerase, a soluble light-requiring enzyme that stereospecifically forms W-cis retinal, was investigated by immunoelectron microscopy and by HPLC. Immunolocalization with polyclonal antibodies shows that the highest concentration of retinal photoisomerase is located in the proximal portion of the primary pigment cells in large aggregates (approximately 2 μm diameter).

Photoisomerase is also located in the peripheral portion of the photoreceptor cells, laterally displaced from the rhabdom, but in much lower concentration. Because of the larger volume of the photoreceptor cells, about half of the total immunoreactivity is associated with the primary pigment cells.

Dissection of the eye with the subsequent use of HPLC to assay for photoisomerase activity showed that most of the photoisomerase activity is associated with tissues near the cornea. The same tissue also supports the reduction of W-cis retinal to W-cis retinol. These biochemical findings are consistent with the immunolocalization of retinal photoisomerase to the high-concentration aggregates in the primary pigment cells that surround the crystalline cones. The major synthesis of W-cis retinol therefore takes place in the primary pigment cells, and the retinoid must be moved into the photoreceptor cells to be available to newly synthesized opsin. The immunoreactivity of the photoreceptor cells appears to reflect the presence of some isomerase without an attached retinoid chromophore.

The ascending projections from the dorsal mesencephalon to the thalamus and pretectum in Rana pipiens were investigated by using the anterograde and retrograde transport of HRP with regard to two major issues:

(1) the degree of tectotopic organization in the projections, and (2) their cells of origin.

The results indicate that the spatial organization of the tecto-thalamic tract is specifically related to the laminar organization of the contributing tectal efferent neurons. Axons of neurons in the superficial portion of tectal layer 8 exit the tectum through layer 9 and travel in the superficial portion of the dorsal and ventral tecto-thalamic tracts and innervate the nucleus lentiformis mesencephali, the posterior lateral dorsal nucleus, and corpus geniculatum. The distribution of terminals within these structures varied with the tectal HRP-injection site. HRP injections in the ventral tecto-thalamic tract retrogradely labeled neurons in the superficial portion of tectal layer 8 across the lateral and caudal portion of the tectal lobe. HRP injections into the dorsal tecto-thalamic tract, at the level of the pretectum, retrogradely labeled pyriform neurons in the superficial portion of tectal layer 8 in the rostral and medial portions of the tectal lobe.

With regard to the deep tectal layers, axons from pyramidal neurons in layer 6 and ganglionic neurons in layer 8 leave the tectum through layer 7, travel in both the dorsal and ventral tecto-thalamic tracts, and are located internal to the axons of the pyriform neurons of superficial tectal layer 8. The majority of the ganglionic neurons project to the posterior lateral ventral nucleus and the anterior lateral nucleus. The distribution of terminals within these nuclei did not display a tectotopic organization.

A second major projection to the thalamus originates from the mesencephalic pretectal gray and innervates the nucleus lentiformis mesencephali, the posterior lateral dorsal nucleus, the anterior lateral nucleus, dorsal and ventral divisions of the ventral lateral thalamus, and the nucleus of Bellonci. Other axons from the mesencephalic pretectal gray terminate in the contralateral, medial portions of the posterior lateral dorsal thalamus, the ventral lateral thalamus, and the anterior lateral nucleus.

The isthmo-tectal projection was also retrogradely labeled following tectal injections of HRP. This pathway travels in the most ventral portion of the ventral tecto-thalamic tract; its axons passed over the lateral margin of the endopeduncular nucleus bilaterally, and crossed the midline in the caudal portion of the optic chiasm. Extensive, bead-like varicosities were observed on these axons both in the endopeduncular nucleus and in the posterior optic chiasm.

These results, taken together with those from other species, strongly suggest that a common organizational plan exists among terrestrial vertebrates with regard to the specific pattern of innervation of pretectal and thalamic nuclei by either the optic tectum or the superior colliculus.

We studied the morphology and center-surround organization of Lucifer Yellow injected OFF- and ON-center bipolar cells in the light-adapted Xenopus retina and the effects of glycine and GABA on their cone-mediated light responses. In both classes of cell, prominent antagonistic surround responses up to 20 mV in amplitude could be evoked without first suppressing the center responses with steady illumination. An additional feature of the light-evoked bipolar cell response was a pronounced (up to –24 mV) delayed hyperpolarizing after potential (DHAP) which followed the depolarizing responses of both classes of bipolar cell.

The morphological features of dye-injected bipolar cells conformed to the general idea of segregation of ON and OFF pathways in the inner and outer interplexiform layer, however, the morphology of axonal arborizations was different for both classes. OFF-center cells ramified symmetrically around the primary branchpoint, whereas ON-center cells had a strongly asymmetrical arrangement of their axonal tree.

The center and surround responses were differentially sensitive to glycine and GABA. Glycine eliminated the antagonistic surround responses in both OFF and ON cells; the center responses were reduced to some extent but were not eliminated. In contrast, GABA affected the hyperpolarizing responses much more strongly than the depolarizing response components. That is, the amplitude of the center response in the OFF cell and the surround response in the ON cell was reduced 80–90% during exposure to GABA, whereas the surround and center depolarizations of OFF and ON cells, respectively, were reduced only 0–10%.

Our findings implicate a role for GABAergic and glycinergic pathways in the center-surround organization of bipolar cells in Xenopus retina. In addition, the results suggest that the pathways mediating center-surround antagonism may be different in OFF-bipolar cells vs. ON-bipolar cells.

The uses of light for cephalopods living at various depths are described. Aphakic apertures are shown in the eyes of Amphitretus and bolitaenids. In cirrate octopods, the eye is an open cup without lens and the retinal rhabdoms are disorganized. The photosensitive vesicles of cephalopods are extraocular receptors present either in the mantle or on the head. In some mesopelagic forms, they serve to compare the downwelling light with that emitted by the animal's own photophores, thus allowing regulation of counterillumination. In bathypelagic species, the photosensitive vesicles are very large and may serve to ensure reproduction at great depths.

Some of the uses of the paired eyes in shallow water species are discussed. The mechanism for visual learning consists of a system for allowing many possible combinations of the output from numerous feature detectors. This begins with a set of columns in the optic lobes, followed by a tangential system. Outputs from the optic lobe lead to either attack or retreat: a third output leads to a memory system of four matrices allowing for interaction among the visual signals and between them and signals of taste or pain. These matrices allow conjunctive interaction between particular sets of signals and the setting up of memories ensuring appropriate responses. The matrices may be considered as analogous with those of the mammalian hippocampus. They include re-excitation among themselves and with the optic lobes. The tactile memory apparatus of the octopus has four similar lobes and also makes use of the four lobes of the visual system. These are therefore striking examples of adaptive networks allowing learned reactions by statistical selection among numerous channels. The anatomy, function, and generalizing powers of these networks emerged from Boycotts's early work, whose significance for computation can now be appreciated.

Bathing the skate retina in a Ringer solution containing a high concentration (100 mM) of potassium ions depolarized the visual cells, depleted the receptor terminals of synaptic vesicles, and suppressed completely the b-wave of the ERG and the intracellularly recorded response of horizontal cells (the S-potential). The depletion of synaptic vesicles was accompanied by a large increase in the extent of the plasma membrane resulting in distortion of the normal terminal profile, i.e. distension of the basal surface and elaborate infolding of protoplasmic extensions. Morphometric analysis showed that despite the changes in vesicle content and terminal structure, the combined linear extent of the vesicular and plasma membranes was unchanged from control (superfusion with normal Ringer solution); the increase in plasma membrane was equivalent to the observed loss of vesicular membrane. When returned to a normal Ringer solution, the terminals rapidly began to reform, and in about 10 min they were morphologically indistinguishable from receptor terminals seen in control preparations. After 30 min in the normal Ringer solution, the amount of membrane associated with the vesicles and the plasma membrane had reverted to control values, and once again the total membrane estimated morphometrically remained essentially the same. Thus, there is an efficient mechanism at the photoreceptor terminal for the recycling of vesicle membrane following exocytosis.

The K+-induced depletion of synaptic vesicles was paralleled by a precipitous loss of responsivity in both the b-wave of the ERG and the S-potential of the horizontal cells. However, after 30-min exposure to the high K+ and a return to normal Ringer solution, the recovery of electrophysiological activity followed a much slower time course from that associated with the structural changes; 60 min or longer were required for the potentials to exhibit maximum response amplitudes. It appears that the rate-limiting step in restoring normal synaptic function following massive depletion of vesicular stores is transmitter resynthesis and vesicle loading rather than vesicle recycling.

Previous studies have suggested that melatonin, released from photoreceptors, may modulate retinal dark-adaptive responses by inhibition of dopamine release from retinal interneurons. We have broadened these studies to examine the effect of melatonin on release of another retinal neurotransmitter, acetylcholine (ACh). The ACh system in rabbit retina has been localized to starburst amacrine cells, which release ACh in response to a variety of experimental stimuli, including direct potassium depolarization, flashing light, and glutamatergic as well as GABAergic inputs. The effect of melatonin on release of endogenously synthesized [3H]-ACh was measured in perfusates from retinas or retinal synaptosomes preloaded with [3H]-choline chloride. Melatonin significantly inhibited ACh release stimulated by potassium in intact retina but not in synaptosomes. Stimulation of intact retina by flashing light or by the glutamate receptor agonist, kainic acid, was also inhibited by melatonin. In contrast, there was no significant effect of melatonin on picrotoxin-induced release. These findings suggest that melatonin does have an inhibitory effect on ACh release, either by direct interaction with the cholinergic amacrine cell, or indirectly via GABAergic but not glutamatergic neurons.

Behavioral and electrophysiological studies of insects demonstrate both spectrally independent and chromatically dependent behaviors and interneurons. This account describes the neuroanatomical identification of two parallel retinotopic subsystems, one supplying descending channels to spectrally independent neck and flight motor circuits, the other supplying polychromatic channels to neuropils associated with leg motor circuits in the thoracic ganglia. In the compound eye, two classes of photoreceptors contribute to each of several thousand sampling units. High-sensitivity, chromatically uniform short-axon photoreceptors (R1-R6) supply the lamina's external plexiform layer and are presynaptic to L1, L2 efferents. These project in parallel with a second system of trichromatic long-axon receptors and the L3 efferent. Both pathways supply columns of the medulla, equal in number to ommatidia. Golgi and cobalt-silver impregnation demonstrates that neurons from the medulla diverge to two deeper regions, the lobula plate and lobula, the former a thin tectum of neuropil dorsal to the more substantial lobula. Layer relationships between medulla neurons and their afferent supply suggest that the lobula plate and lobula are each supplied by one or the other, but not both, of the two parallel subsystems. Independence of the two parallel pathways is suggested by ablation of the photoreceptor layer leading to selective degeneration of the motion-sensitive lobula plate neuropil. In addition, octets of small-field neurons associated with the R1-R6/L1, L2 pathway give rise to synaptic complexes with motion-sensitive neurons of the lobula plate. A variety of behavioral and electrophysiological studies provide supporting evidence that certain insects possess parallel visual pathways comparable to the magnocellular and parvocellular subsystems of primates.

We have examined some of the physiological effects associated with the replacement of extracellular Na+ with Li+ in nominally Ca2+-free saline in the ventral photoreceptors of the horseshoe crab Limulus polyphemus. We observed that replacement of Na+ saline with Li+ saline induced larger voltage-activated inward currents with similar voltage dependence. These currents were absent in Tris+ saline. Anode-break excitation was maintained in Li+ saline but blocked in Tris+ saline. Regenerative events associated with quantum bumps in dark-adapted cells illuminated with dim lights were maintained in Li+ saline. Regenerative events associated with responses to moderately bright illumination were also maintained in Li+ saline. The post-illumination hyperpolarization associated with the Na+/K+-exchange pump (Brown & Lisman, 1972) was present after brief exposure to Li+ saline but disappeared after longer exposure. Following return to Na+ saline, the post-illumination hyperpolarization reappeared. We conclude that (1) Li+ permeates the voltage-dependent Na+ channel, GNa(V), in the photoreceptor plasma membrane; (2) Li+ supports voltage-activated physiological events normally mediated by Na+; and (3) Li+ substitution briefly supports and later inhibits the electrogenic effects of the Na+/K+-exchange pump. The effects of external Li+ on cellular physiology have implications for the interpretation of other studies employing Li+ extracellularly.

Effects of the major glutamate receptor agonists, kainate (KA), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), quisqualate (QA), N-methyl-D-aspartate (NMDA), L-α-amino-4-phosphonobutyrate (L-AP4), and trans-l-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on horizontal cells (HCs) were studied in superfused larval tiger salamander retina. 20 μM of KA, AMPA, and QA mimicked the action of 3 mM glutamate in the absence and presence of 1 mM Co2+-20 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the actions of KA and AMPA, but not those of QA and glutamate, indicative of the existence of CNQX-resistant QA receptors in the tiger salamander HCs. Prolonged application of ACPD hyperpolarized the HCs and enhanced the light responses, probably by shifting the resting HC voltage (Er) to a more hyperpolarized position. It is possible that the KA, AMPA, and CNQX-resistant QA receptors are involved in mediating the postsynaptic light responses in HCs, and ACPD receptors are involved in sensitivity adjustment of the HC responses.

Monoclonal antibodies to human leucocyte antigens, including anti-CD45 and anti-CD68, have been used to describe microglia in flatmounts of normal adult human retina for the first time. Anti-CD45 (the leucocyte common antigen) intensely labeled large numbers of cells in a regular distribution across the retina; anti-CD68 and anti-macrophage antibodies labeled fewer cells with distinctive morphologies, suggesting the presence of subpopulations of microglia in the human retina expressing leucocyte antigens.

Immunocytochemical techniques were used to localize strychnine-sensitive glycine receptors in cat retina. Light microscopy showed staining in processes ramifying throughout the inner plexiform layer and in cell bodies of both amacrine and ganglion cells. At the electron-microscopic level, receptor immunoreactivity was seen to be clustered at sites postsynaptic to amacrine cells. In contrast, bipolar cells were neither presynaptic nor postsynaptic elements at sites of glycine receptor staining. Double-label studies verified the presence of glycine immunoreactivity in amacrine terminals presynaptic to glycine receptors. These findings support a role for glycine as an inhibitory neurotransmitter in amacrine cells.

The dopamine (DA) innervation, labeled by tyrosine hydroxylase immunohistochemistry in a wholemounted human retina, is described in the avascular area of the fovea. Eleven DA neurons give rise to this innervation, among which five are interplexiform cells, so that the DA innervation consists of two plexuses: one is internal and is formed by the dendrites of all of the DA cells, and the other is external and is formed by the scleral processes of the interplexiform cells. Five concentric zones are delineated according to the focal plane in which the internal DA plexus is observed. The central zone 1 contains DA processes crossing in all directions. Zones 2 and 3 do not contain any cell bodies. In zone 3 the internal plexus begins to undergo a concentric arrangement, which is clearly observed in zones 4 and 5. The external DA innervation displays a different appearance in zones 1, 2, and 3, in which it consists of vertically oriented thin processes and terminals penetrating the outer nuclear layer, vs. zones 4 and 5 in which it consists of both the same type and horizontal processes lying in the outer plexiform layer. On the basis of DA-innervation appearance and distribution of labeled and unlabeled cell somata, it was concluded that zones 1, 2, and 3 contained the DA innervation of the foveola. DA processes filtering between photoreceptor cells are particularly well-observed in this region. This anatomical study of the DA innervation in the human fovea leads to a better understanding of the important role of DA in primate central vision and can be used as a reference for an approach of macular pathology.

Retinae of the crab Leptograpsus which had been maintained on a 12-h light/12-h dark cycle were cultured in vitro and exposed to 1 μM okadaic acid (OKA) at 0.75 h before light onset. Control retinae were subjected to the same routine and sampled at the same times without OKA treatment. At the concentration used, OKA totally inhibits types 1 and 2A protein phosphatases, minimally inhibits type 2B, and does not affect type 2C. 1 μM OKA provoked a diminution of rhabdom diameter measured at the level of the photoreceptor nuclei in the dark, some ommatidial cartridges being stripped of rhabdomeral microvilli altogether. After 1-h illumination (225–320 lux), further reduction of rhabdom diameter was modest in control retinae but precipitate in those treated with OKA. After 2 h, control rhabdom diameters showed a further, not significant, decline, but OKA had induced a resynthesis of massive structures with the light-microscopic appearance of rhabdoms. Electron microscopy revealed that they were heterogeneous and of the following kinds: (1) a minority of rhabdoms with normally disposed but distorted microvilli; (2) rhabdoms in the throes of events that parody normal assembly; and (3) rhabdomal volumes occupied by saccular organelles or by pleats or ruffles of irregular architecture. The cytoplasm of all such receptors was packed with free and bound ribosomes and endomembranes. The sequence of events parallels that seen during light-induced degeneration of photoreceptors of the Drosophila mutant w rdgBKS222. Preliminary experiments show that a protein kinase activator SC-9 mimics many of these effects in the dark in the presence of 1 μM OKA. As a working hypothesis, it is proposed that light activates protein kinases via diacylglycerols generated by the phototransduction cascade, and that in both crab retinas challenged with OKA and retinas of rdgBKS222 activation of a nuclear regulatory protein by hyperphosphorylation provokes a runaway transcription whose selectivity and extent remain to be determined.

We have examined the effects of rearing kittens with a unilateral convergent strabismus, induced surgically at 3 weeks of age, on the binocularity (ocular dominance) and receptive-field position of neurons in the motion-sensitive lateral suprasylvian (LS) area of cat extrastriate cortex. Data were compared to those obtained from area 17 in the same animals, and from the two areas of cortex in normal adult cats. Interocular alignment of the operated cats was assessed in alert adults using corneal reflex photography and during recording from the positions of retinal landmarks under paralysis. The strabismus magnitude in each operated cat was calculated by comparison with equivalent data from the normal animals.

Strabismus always caused a major loss of binocularity in area 17. The remaining binocular neurons had receptive-field (RF) pairs arising from positions of normal correspondence in the two retinae and would thus have been responsive to different regions of visual space through the misaligned eyes in the alert animal. In area LS, the effects were dependent on the strabismus magnitude. In the group of four cats with pronounced strabismus (18–30 deg crossed), a loss of binocularity occurred in area LS equivalent in severity to that in area 17. The majority of the remaining binocular LS neurons possessed RF pairs in normal retinal correspondence and would thus, in the alert animal, have received spatially disparate visual input through the two eyes. This also occurred in three other cats with more moderate strabismus (11–15 deg crossed), although only a small breakdown in the binocularity of area LS was apparent. The group of cats with mild strabismus (≤10 deg crossed) had normal proportions of binocular neurons in area LS. In three of these cats, the maintenance of binocularity was accompanied by shifts in RF position, with visual inputs arising from anomalous retinal locations. These shifts compensated, in part, for the strabismus angle present in each cat, so that most of the binocular LS neurons would have received inputs from regions of visual correspondence through the misaligned eyes when the animal was alert.

Similar mechanisms could afford a basis for the binocular visual compensations that occur in humans with small-angle strabismus of early onset. If so, anomalous retinal correspondence in such individuals would have as a locus areas of extrastriate cortex with a role in motion perception, and would involve alterations to the neural substrate underlying normal binocular vision.