Recent immunocytochemical studies indicate the existence of several classes of peptide- (PRGC) and catecholamine-containing retinal ganglion cells in anurans, birds, and mammals. Different classes of PRGC project to discrete and seemingly unique layers in the retino-recipient portion of the anuran and avian optic tectum. Peptide-containing retinofugal projections to the frog tectum originate early in development, and are reestablished by some classes of PRGC during regeneration of the optic nerve. These findings indicate that chemically specific, parallel retinofugal pathways presumably subserve different functional aspects of vision in vertebrates. Exciting prospects for research include the correlation of physiologically with immunocytochemically defined classes of retinal ganglion cells, the analysis of the possible role of neuroactive peptides in retinofugal transmission, and the pharmacological manipulation of putative peptidergic retinofugal pathways to analyze their role in visual function.

Bipolar cells make reciprocal synapses with amacrine cells in the inner plexiform layer; both feedforward connections and feedback connections are present. The physiological properties of the feedback synapse have not been well described. Since some amacrine cells are thought to be GABAergic, we examined bipolar cells for feedback input from γ-aminobtyric acid (GABA)ergic amacrine cells. Solitary bipolar cells were dissociated enzymatically from the goldfish retina. Cells were voltage clamped with a patch pipette and their GABA sensitivity was examined. GABA evoked responses in all bipolar cells with a large axon terminal, which were identified to be the rod dominant ON type, and in some bipolar cells with a small axon terminal. The highest GABA sensitivity was located at the axon terminal. The least effective dose was as low as 100 nM. A small insignificant response of high threshold was evoked when GABA was applied to the dendrite and soma. GABA increased the Cl conductance and caused membrane hyperpolarization. The bipolar cells had the GABAA receptor coupled with a benzodiazepine receptor. The GABA-evoked response was not susceptible to Co ions, which suppressed the GABA-induced responses in turtle cones by 50% at 5 fiM concentration. Incomplete desensitization was observed, suggesting that the GABAergic pathway seems capable of transmitting signals tonically. The present results strongly indicate that the rod-dominant ON-type bipolar cells and some bipolar cells with a small axon terminal receive negative feedback inputs from GABAergic amacrine cells.

A serial-lesion technique was used to investigate interactions in visual processing between telencephalic components of the pigeon visual system. Pigeons were trained to discriminate pairs of stimuli that differed in color, intensity or pattern. After mastering the discrimination tasks, they were assigned to one of three groups. The first group (WI-EII) received lesions of the visual Wulst and were retested. After the discrimination tasks were again mastered, a second set of lesions was made, this time in the ectostriatum. The birds were tested once again after the second surgery. The second group (EI-WII), underwent the same sequence of events except that the order of the lesions was reversed. In the third group (E + W), lesions of both the visual Wulst and ectostriatum were made in a single operation, followed by retesting. The performance after the first lesion of the subjects in each of the two-stage lesion groups was typical of performance after such lesions; i.e. the birds with visual-Wulst lesions showed little or no impairment on any of the tasks, whereas the pigeons with ectostriatum lesions showed considerable deficits in intensity and pattern discrimination, which diminished after prolonged retraining. In contrast, the pigeons in the one-stage group (E + W) showed profound deficits that appeared to be permanent. The performance after the second operation of the WI-EII group was the same as that of pigeons with lesions of ectostriatum alone; i.e. destruction of ectostriatum first or second resulted in the same duration of impairment. The performance of the EI-WII group after its visual Wulst lesion, however, was similar to that observed in the E + W group. The results are interpreted as a reflection of parallel processing within the avian visual system; i.e. the presence of an intact tectofugal pathway may mask the effects of thalamofugal pathway interruption.

Recent studies have shown that several receptor populations in cat visual cortex undergo alterations in their laminar distributions during postnatal development (Shaw et al., 1984a, b; 1986b). These redistributions occur during the first few months of postnatal life, coincident with the physiologically defined critical period for cortical plasticity. In the present communication, we demonstrate that receptor redistributions can be prevented from occurring, or progressing once started, by surgically isolating the visual cortex at appropriate postnatal ages. These data suggest that the maturation of the chemical circuitry of the visual cortex is dependent on factors of extrinsic origin.

The orientation selectivity, ocular dominance, and binocular disparity tuning of 272 cells in areas 17 and 18 of barbiturate-anesthetized, paralyzed cats were studied with automated, quantitative techniques. Disparity was varied along the axis orthogonal to each cell's best orientation. Binocular correspondence was established by means of a reference electrode positioned at the boundary of lamina A and Al in the area centralis representation of the lateral geniculate nucleus. Measures were derived that expressed each cell's disparity sensitivity and best disparity and the shape and slope of its tuning curve. Cells were found that corresponded to categories described by previous authors (“disparity-insensitive,” “tuned excitatory,” “near,” and “far” cells), but many others had intermediate response patterns, or patterns that were difficult to categorize. Quantitative analysis suggested that the various types belong to a continuum.

No relationship could be established between a cell's best orientation and its ocular dominance or any aspect of its disparity tuning. There was no relationship between a cell's ocular dominance and its sensitivity to disparity. Ocular dominance and best disparity were related. As reported by others, cells with best disparities close to zero (the fixation plane) tended to have balanced ocularity, while cells with best disparities in the near or far range had a broad distribution of ocular dominance. Among cells with receptive fields near the vertical meridian, those preferring far disparities tended to be dominated by the contralateral eye, and those preferring near disparities by the ipsilateral eye. It is suggested that this relationship follows from the geometry of near and far images and the pattern of decussation in the visual pathway. There was a significant grouping of cells with similar best disparities along tangential electrode tracks. We believe that this grouping is due to the columnar organization for ocular dominance and the relationship between ocular dominance and best disparity. No evidence was found for a columnar segregation of disparity-sensitive and disparity-insensitive cells.

Nucleus rotundus and nucleus dorsolateralis posterior (DLP) are the thalamic components of two parallel pathways within the tectofugal division of the pigeon visual system. An earlier study (Hodos, Weiss & Bessette, 1986) had shown that lesions in direct telencephalic recipients of projections from rotundus and DLP produced postoperative elevations in size-difference thresholds only if the lesion included both structures. What was not revealed by their study was whether the integrity of both thalamic components is necessary for pigeons to discriminate small differences in the size of stimuli or whether the birds could still make the discrimination with only one of the two nuclei intact. This question was particularly important because no prior behavioral evidence existed to indicate that DLP plays a role in visual information processing. Therefore, 14 pigeons were tested preoperatively using a variant of the method of constant stimuli to determine the smallest difference between the size of two annuli that the subjects could discern. The comparison stimuli, which were presented in a successive discrimination procedure, ranged from 3.5–15 mm in diameter. After surgery, in which lesions were placed bilaterally in rotundus, DLP, or both structures, the subjects' size-difference thresholds were again determined. Combined lesions of rotundus and DLP resulted in impaired psychophysical performance. The postoperative behavior was characterized by initial elevations in threshold followed by a gradual improvement in performance. Some birds returned to their preoperative level. By comparison, subjects with lesions in rotundus or DLP alone showed an immediate return to their preoperative sensitivity level. These results indicate that both nuclei can process information about the size of visual stimuli. Moreover, the processing that occurs within either nucleus is sufficient for the pigeon to discriminate size differences. The present experiment provides the first behavioral evidence that DLP participates in visual information processing.

Cortical connections of area 18 (V-II) and part of the dorsolateral visual area (DL) were determined in squirrel monkeys with single and multiple injections of the sensitive bidirectional tracer, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Injections were placed into portions of area 18 or DL on the dorsolateral surface of the brain, patterns of label were examined in brain sections cut parallel to the surface of physically flattened cortex, and comparisons were made with alternate brain sections reacted for cytochrome oxidase (CO) or stained for myelinated fibers. Major results are as follows. (1) Area 18 was identified by a characteristic alternation of dense and light CO bands crossing its width; the middle temporal visual area (MT) was CO dense; the dorsolateral area (DL) was less reactive, with rostral DL (DLR) lighter than caudal DL (DLC); area 17 had clear CO puffs in the supragranular layers. (2) Intrinsic connections revealed in area 18 included a narrow 100–200 μm fringe of less dense label around each injection core, label unevenly distributed in small clumps within 1–2 mm of injection sites, and clumps of transported label up to 6 mm from injection sites. (3) Single and multiple injections in area 18 produced patterns of labeled cells and terminations in area 17 that ranged from lattice- to puff-like in surface-view distribution. With multiple area 18 injections, regions of area 17 could be found where transported label was concentrated in CO puffs, avoided the CO puffs, or overlapped both puff and interpuff divisions of cortex. The labeled regions of area 17 were somewhat larger than the injection sites, suggesting some convergence from area 17 to area 18. (4) The major rostral connections of area 18 were with caudal DL (DLC). Rostral DL (DLR) was largely free of transported label. Single injection sites in area 18 resulted in several large clumps of label separated by regions of sparse or no label in DLC. Injections in lateral area 18 produced lateral foci of label in DL, while more medial injections produced more medial foci. However, following multiple injections into area 18 that included the representation of central vision, a continuous 2–3-mm-wide band of infragranular labeled cells extended from area 18 caudally to MT rostrally in the presumed location of central vision in DLC and DLR. (5) Injections in area 18 produced foci of label in MT. Label was more dorsal in MT with more dorsal injection sites in area 18. (6) Injections in area 18 resulted in sparse label in cortex within the inferior temporal sulcus and in cortex in the location of the frontal eye field. (7) Callosal connections of area 18 were with areas 17, 18, DL, and sparsely with MT. Multiple injections in area 18 produced a narrow, dense strip of label along the contralateral 17/18 border. Most of this label was in area 18, but small protrusions of label extended into area 17, and small separate foci of label were found displaced slightly into area 17. Fingers of callosal connections extended rostrally from the caudal border to cross up to half of the width of medial area 18 and the entire width of lateral area 18 where central vision is represented. Patchy callosal connections were found with DLC. (8) Injections in caudal DL confirmed the observation from area 18 injections that major connections of DLC are with area 18. Injections in DLR produced scattered, small foci of label in area 18 near the rostral border, as well as puffs of intrinsic connections, connections with MT, and with cortex rostral to area 18 medially.

The major conclusion stemming from the present results is that the DL region consists of at least two fields, with the caudal portion, DLC, receiving major inputs from area 18, and the rostral portion, DLR, having little input from area 18.

We have investigated responses in proximal retina of the cat that contribute to two kinds of electroretinogram (ERG) recordings: (1) the pattern ERG, a light-adapted response and (2) the threshold and near threshold ERG, a dark-adapted response (Sieving et al., 1986a, 1986b; Sieving & Steinberg, 1985). In intraretinal, extracellular recordings, two negative-going responses were identified that are maximal around the inner plexiform layer, and distinct from PII, which is maximal in distal retina: under light-adapted conditions, a spatially tuned response at light onset and light offset, the “M-wave” (previously described in cold-blooded animals by Karwoski & Proenza (1977, 1980)), and under dark-adapted conditions, the scotopic threshold response, or “STR,” a response at light onset. The results under dark-adapted conditions are examined in more detail here.

The STR is a very sensitive response whose threshold is 1.5–2.0 log units below that of the dc-component of PII and therefore well below the threshold of the a-, b-, and c-waves. It saturates about 2.4 log units below rod saturation. The STR contributes a negative-going potential to the dark-adapted ERG that is dominant near threshold; while PII (dc-component and b-wave) contributes a positive-going potential that is dominant at higher intensities (Sieving et al., 1986b). Investigation of the mechanism of the proximal retinal responses that contribute to the ERG supports a K+-Müller cell hypothesis of their origin.

The elimination of retinogeniculate afferents from one eye on embryonic day 44 (E44) has pronounced effects on the formation of the cellular laminae in the cat lateral geniculate nucleus (LGN). Only two laminae form: a dorsal, “magnocellular” layer, and a ventral, “parvocellular” layer. Soma size measurements and previously reported patterns of termination of retinogeniculate axons suggest that the dorsal lamina is a coalescence of the normal A-laminae and the dorsal, magnocellular division of layer C, while the ventral layer is a composite of the parvocellular sublamina of layer C and the remaining C-laminae. This is a novel pattern of lamination in the LGN that differs from that found in the normal nucleus, not only in that there are now only two cell layers rather than the normal five, but also in that the interlaminar zone occurs in an abnormal location. This result is markedly different from that observed in other species where interlaminar zones present after early monocular enucleation are a subset of the ones which would normally be present. We suggest that, in the absence of ongoing binocular interactions, interactions between functionally distinct retinal ganglion cell classes from the remaining eye may direct the formation of cell laminae in the LGN, even when such interactions are not normally operative.

The neural circuitry underlying movement detection was inferred from studies of amacrine cells under whole-cell patch clamp in retinal slices. Cells were identified by Lucifer yellow staining. Synaptic inputs were driven by “puffing“ transmitter substances at the dendrites of presynaptic cells. Spatial sensitivity profiles for amacrine cells were measured by puffing transmitter substances along the lateral spread of their processes. Synaptic pathways were separated and identified with appropriate pre- and postsynaptic pharmacological blocking agents.

Two distinct amacrine cell types were found: one with narrow spread of processes that sustained excitatory synaptic current, the other with very wide spread of processes that transient excitatory synaptic currents. The transient currents found only in the wide-field amacrine cell were formed presynaptically at GABAB receptors. They could be blocked with baclofen, a GABAB agonist, and their time course was extended by AVA, a GABAB antagonist. Baclofen and AVA had no direct affect upon the wide-field amacrine cell, but picrotoxin blocked a separate, direct GABA input to this cell.

The narrow-field amacrine cell was shown to be GABAergic by counterstaining with anti-GABA antiserum after it was filled with Lucifer yellow. Its narrow, spatial profile and sustained synaptic input are properties that closely match those of the GABAergic antagonistic signal that forms transient activity (described above), suggesting that the narrow-field amacrine cell itself is the source of the GABAergic interaction mediating transient activity in the inner plexiform layer (IPL). Other work has shown a GABAB sensitivity at some bipolar terminals, suggesting a population of bipolars as the probable site of interaction mediating transient action.

The results suggest that two local populations of amacrine cell types (sustained and transient) interact with the two populations of bipolar cell types (transient forming and nontransient forming). These interactions underlie the formation of the change-detecting subunits. We suggest that local populations of these subunits converge to form the receptive fields of movement-detecting ganglion cells.

The trajectories of saccadic eye movements evoked electrically from many brain structures are dependent to some degree on the initial position of the eye. Under certain conditions, likely to occur in stimulation experiments, local feedback models of the saccadic system can yield eye movements which behave in this way. The models in question assume that an early processing stage adds an internal representation of eye position to retinal error to yield a signal representing target position with respect to the head. The saccadic system is driven by the difference between this signal and one representing the current position of the eye. Albano & Wurtz (1982) pointed out that lesions perturbing the computation of eye position with respect to the head can result in initial position dependence of visually evoked saccades. It is shown here that position-dependent saccades will also result if electrical stimulation evokes a signal equivalent to retinal error but fails to effect a complete addition of eye position to this signal. Also, when multiple or staircase saccades are produced, as during long stimulus trains, they will have identical directions but decrease progressively in amplitude by a factor related to the fraction of added eye position.

The existence in cat cortex of linearly operating simple cells with relative spatial-frequency bandwidths of between 0.5 and 1 octave is confirmed.

In this study we examine the postnatal development of retinogeniculate axons projecting to the magnocellular (M axons), parvocellular (P axons), and koniocellular (K axons) layers of the lateral geniculate nucleus (LGN) in the prosimian primate, Galago crassicaudatus, in order to: (1) understand how individual retinogeniculate axons in primates mature postnatally, and (2) determine whether differences exist in the development of separate classes of axons that are known to be presynaptic to physiologically distinct cells in adults. In galagos, magnocellular, parvocellular, and koniocellular LGN layers contain Y-, X-, and W-like physiological cell classes, respectively (Norton & Casagrande, 1982).

In vitro and in vivo optic tract bulk injections of horseradish peroxidase (HRP) were made in animals ranging in age from the day of birth (P0) to adulthood. Two hundred and fifty axonal arbors were completely reconstructed from serial sections and examined qualitatively for general features of maturity and compared quantitatively for changes in shape, arbor width, area, volume, bouton number, and bouton density.

Our results confirm that in adult galagos M arbors are large and radially symmetric; P arbors are medium sized and elongated perpendicular to layer borders; K arbors are small and generally oriented parallel to layer borders. At birth, M, P, and K arbors, although still distinct and confined to layers, are qualitatively and quantitatively immature. Both the pattern and pace of maturation differ between classes. Overall, M arbors mature before P arbors which in turn mature before K arbors. Within classes, arbors representing central vision appear to develop about a week ahead of those representing peripheral vision; no differences are evident between the development of crossed and uncrossed arbors. In no case do arbors exhibit a period of postnatal exuberance, wherein arbors are larger than those of the adult as reported for cat X retinal axons. However, in width and bouton density P arbors are mature at P0 and thus occupy relatively more space in the nucleus compared to adult. All arbors mature rapidly and appear adult-like by the 4th or 5th postnatal week.

The autoradiographic distribution of [3H]nicotine binding sites was examined in the superior colliculus in normal rats and cats, and in animals in which one or both eyes were removed. [3H]Nicotine binding sites in normal animals were densely concentrated in the superficial layers of the colliculus corresponding to the zone of termination of optic nerve fibers. Following bilateral enucleation, [3H]nicotine binding in the superficial collicular layers was drastically reduced. Unilateral enucleation markedly reduced [3H]nicotine binding sites in the colliculus contralateral to the removed eye, with little effect on the ipsilateral colliculus. These results provide further evidence that nicotinic acetylcholine receptors have a presynaptic location on optic tract terminals and may therefore modulate retinotectal transmission in both the rat and cat visual system.

Axons containing serotonin (5-hydroxytryptamine, 5-HT) in the lateral geniculate nucleus of Macaca monkeys were stained using light or electron microscopic (EM) immunocytochemical labeling techniques. 5-HT labeled axons were sparsely and homogeneously distributed throughout the entire nucleus. Small varicosities were located irregularly along each axon giving them a beaded appearance. Examination of these axons at the EM level revealed that the varicosities contained synaptic vesicles that were variable in size and shape. Nearly all of the varicosities lacked synaptic contacts; only two out of over two hundred labeled varicosities appeared to form a synaptic contact, and serial sections through ten varicosities showed no discernible pre- or postsynaptic membrane specializations. 5-HT labeled axon varicosities were not observed to be preferentially located in proximity to any specific neuronal structures at either the light or EM level. 5-HT varicosities were estimated to form about 1% of the profiles containing synaptic vesicles in the neuropil of the lateral geniculate nucleus.

We conclude that axons containing serotonin in the lateral geniculate nucleus release this neurotransmitter to act in a neuromodulatory manner throughout the neuropil, probably to set a general level of neuronal excitability.