Tunicamycin (TM), an inhibitor of dolichylphosphate-mediated protein glycosylation, was injected intravitreally into the eyes of diurnal rodents with cone-dominated retinas. Injection of 1 μg of the B2 isomer led to a progressive degeneration of the photoreceptor outer segments and disruption of the RPE-photoreceptor interface that took place over a 10-day period. Cone outer segments were shortened by postinjection day 6 and virtually absent by day 9. The microvilli that normally protrude from the apical surface of the retinal pigment epithelium were replaced by a fringe of shortened processes. The other retinal layers showed no morphological evidence of disruption. Retinal sensitivity, as measured by electroretinographic b-wave threshold, showed a significant and progressive decline over the 10-day course of the experiment that paralleled the disruption of retinal morphology. These results suggest that TM leads to similar morphological and electrophysiological effects on rod and cone photoreceptors.

The action spectrum of the ERG b-wave was measured under dark-adapted conditions in intact goldfish (Carassius auratus). It is substantially broader than the absorption spectrum of goldfish rod porphyropsin. Neither prolonged dark adaptation nor removal of possible efferent neural activity affected its shape. Moreover, a 682-nm background did not produce a selective loss of sensitivity to long wavelengths. The results imply that the spectral sensitivity of the b-wave in dark-adapted goldfish reflects the influence of at least two photoreceptor types which act as a single univariant mechanism near absolute threshold.

Using fractions of the protein spectrum of the cat retina as immunogens, we have generated antibodies with substantial specificity for the Müller cells of the retina of cat, rabbit, guinea pig, and rat. The antibodies appear to bind to the filamentous components of the Müller cells and allow demonstration of the pattern of Müller cell endfeet at the inner surface of the retina, best seen in wholemount preparations. In sections and at the edge of wholemount preparations the somas and processes of the cells can be observed. Müller cells are more evenly distributed over the retina than ganglion cells, indicating that their proliferation continues during the differential growth of retina which continues into postnatal life. The morphology and distribution of the endfeet varies with the structures present at the inner surface of the retina. Where the axon bundles are thick, the endfeet are relatively small and are confined to narrow rows between bundles. Müller cell endfeet are also separated widely by large blood vessels. In both situations, it seems likely that Müller cells and astrocytes both contribute, perhaps competitively, to form the glia limitans of the inner surface of the retina. Where the somas of neurones are densely packed in the ganglion cell layer, the endfeet are small and numerous, forming rings around the somas. Where axon bundles, vessels, and somas are sparse, the endfeet appear largest and form a regular array.

Selective agonists and antagonists were employed to determine the role of indoleaminergic amacrine cells in the generation of the light-evoked responses and spontaneous activity of direction and orientation selective cells. Perfusion with 5-HT2 antagonists reduced the spontaneous activity and both the leading and trailing edge responses of ON/OFF direction selective cells. 5-HT1a agonists had a similar effect on this class of cell, namely, a reduction of light-evoked and spontaneous activity. Results from ON-center and OFF-center orientation selective cells were consistent with those obtained from direction selective cells in that no disruption of direction or orientation selectivity was observed during perfusion of these drugs. These data suggest that the indoleaminergic cells are not directly involved in the generation of the trigger features of complex ganglion cells, but may be facilitating synaptic transmission in the inner retina. This function is discussed relative to the connectivity of the rod bipolar cells and the putative indoleaminergic amacrine cells. The similarity of the effects of 5-HT1a agonists and 5-HT2 antagonists supports the hypothesis, developed during our prior studies of brisk ganglion cells, that these two receptor classes mediate antagonistic processes in the target neurons.

The distribution and ultrastructure of neurons and neuropil labeled by an antiserum to gamma-aminobutyric acid (GABA) were examined in the lateral geniculate nucleus (LGN) of the tree shrew (Tupaia belangeri). The LGN of this species segregates center type and cell class into three distinct pairs of laminae: a medial pair (laminae 1 and 2) containing ON-center cells, a more lateral pair (4, 5) containing OFF-center cells, and 2 laminae (3, 6) containing W-like cells. The relationship between this laminar segregation and the distribution of GABA immunoreactivity was investigated in the present study. GABA-immunoreactive neurons and neuropil were present in all six of the laminae. However, both the density of labeled cells (adjusted for neuronal density across laminae) and the density of labeled neuropil showed a medial-to-lateral gradient. The adjusted density of labeled cells was higher laterally than medially, and the density of labeled neuropil was significantly greater in the more lateral OFF-center laminae and W-like laminae than in the medial two ON-center laminae. Thus, inhibitory, GABAergic influences may modulate to different degrees the visual signals in the ON, OFF, and W pathways. Labeled cells had a mean cross-sectional area (107 μm2) approximately one-half that of unlabeled cells (216 μm2). They constitute 16–34% of the neurons in the LGN. At the electron microscope level, three different kinds of labeled profile were observed. Vesicle containing profiles like the F2 profiles of cat were postsynaptic to retinal terminals and presynaptic to conventional dendrites. Fl axon terminals with dense clusters of vesicles were also labeled as were some myelinated axons. Another labeled profile, which we suggest should be called an F3 process, was a large dendrite of irregular caliber with punctate groups of vesicles near the synapse. Our results suggest that GABAergic circuitry is an important part of the functional organization in the LGN of the tree shrew.

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.

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.

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 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.