Physiological studies of intracellular messengers frequently employ intracellular injections of large molecules that either monitor or modulate the metabolism of the messenger cascade. Injected molecules have unknown mobility in the cytosol and unknown accessibility to various cytosolic compartments, including those postulated to be traversed by intracellular messenger molecules. In order to determine whether injected molecules have access to the confined spaces through which messenger molecules must diffuse, we injected 5-nm colloidal gold or horseradish peroxidase, or both, into Limulus ventral photoreceptors. Injections were made by applying pressure pulses to the back of an intracellular micropipette that also monitored membrane voltage. The tissue was fixed at varying times after injection and processed for electron microscopy by conventional techniques. Cells fixed 1–3 min after injection contained HRP reaction product only in the cell body. HRP reaction product was found at varying distances down axons in direct relation to the interval between injection and fixation. Colloidal gold particles were found throughout the cell body but not in axons of tissue fixed 1–3 min after injection. Both HRP reaction product and 5-nm colloidal gold particles were observed within the microvillar projections of internal and external rhabdomere, as well as within the extracisternal spaces of endoplasmic reticulum. We conclude that large molecules injected from an intracellular micropipette into an arbitrary locus of ventral photoreceptor cells have access to all of the presumed sites of the phototransduction cascade.

Ungulates have been classified as having arrhythmic eyes in the sense that they contain features appropriate both to diurnal and nocturnal life. The former is typically associated with multiple classes of cones and a color-vision capacity. To see if an arrhythmic animal has these features, the number of cone classes was determined and the spectra of these cones were measured in a common ungulate, the domestic pig (Sus scrofa). Examination with electroretinogram (ERG) flicker photometry revealed the presence of two classes of cones in the pig's eye having average maximum sensitivity (λmax) at 439 nm and 556 nm, respectively. This ungulate thus has the requisite retinal basis for dichromatic color vision.

Single frog rods consisting of the outer segment and the ellipsoid were investigated by the whole-cell patch-clamp technique. When the recording pipette was filled with a simple intracellular medium containing potassium as the principal cation, a slow increase in dark voltage (hyperpolarization) associated with a decay of the photoresponses was observed. The hyperpolarization started at a dark voltage of −27 ± 8 mV, followed an exponential course, and leveled out at −52 ± 6 mV. The time constant was proportional to the access resistance of the preparations. With a pipette medium containing a 0.5 or 1.0 μM cGMP, the initial dark voltage was shifted to more positive values and the tendency of hyperpolarization was clearly attenuated. Similar results were obtained with 1 mM GTP. The effects of GDP and of ATP were less significant. In experiments with 1 mM GTP plus 1 mM ATP, the dark voltage behaved as in experiments with only GTP. The stabilizing action of GTP was amplified by EGTA so that with 1 mM GTP plus 1 mM free EGTA the dark voltage was stable at a level of −15 mV. It is concluded that the preparations lose intracellular components such as cGMP and GTP by diffusion into the recording pipette and that the losses are prevented or reduced when the pipette medium contains these nucleotides in nearly physiological concentrations. For the internal transmitter cGMP, the results suggest that its free concentration does not exceed 1 μM.

Autoradiographic techniques were used to label [3H]-adenosine and [3H]-cyclohexyladenosine accumulating cells in rabbit, mouse, and ground squirrel retinas. Immunohistochemical methods revealed the distribution of cells that stained for endogenous adenosine. Comparisons of these two markers revealed for all three species that the distribution of specific subpopulations of retinal cells that store or accumulate the purine nucleoside, adenosine, is similar. For all three species, cells localized in the ganglion cell layer accumulated adenosine and exhibited adenosine-like immunoreactivity (ALIR). A smaller proportion of cells localized in the inner nuclear layer were labeled for ALIR, while a larger proportion of cells in this layer accumulated adenosine. Subtle differences between species are presented. However, the general similarities of the distribution of these two putative purinergic markers supports the evidence that a discrete adenosinergic neurotransmitter/modulatory system is present in the retina.

Differential stretch of a retinal surface with an initially uniform cell density has been repeatedly implicated as one of the developmental mechanisms that produces the topographic organization of cell density in the adult retina, notably the area centralis or visual streak versus peripheral regions. It is known that intraocular pressure is required to produce the normal conformation and thinning of the retina during development. We tested the possibility that the retina has elastic properties that might permit differential stretch in conjunction with intraocular pressure. The relative deformation of the retina containing the presumptive area centralis was compared to the deformation of peripheral retina at equivalent applied fluid displacements in 7–12-day-old cats. The peripheral retina deformed significantly more, consistent with the hypothesis that differences in the local elasticities of the developing neural retina contribute to its characteristic topographic changes. Thus, a biomechanical property of the growing eye may contribute to the mechanism by which the pattern of the visual array is sampled.

The formation of topographic maps requires not only that afferents synapse with the appropriate targets, but that the spatial relationships between the afferents be maintained. During development, in addition to the formation of the topographic map, the connectivity patterns responsible for the receptive-field properties of the target cells are being formed. The extent of interaction between these two processes is unknown. The present study addresses this question by manipulating afferent/target ratios during development, thus altering the topography of the map, and studying the effects of this alteration on the receptive-field properties of single target cells in the adult.

Partial unilateral lesions of the superior colliculus (SC) were made in neonatal hamsters. These lesions result in a compression of the retinotopic map onto the remaining collicular fragment. Single cells were recorded from the superficial gray layer of the SC in the adult in response to visual stimuli. Receptive-field properties observed in lesioned animals were compared to those in normal animals and in sham operates.

Receptive-field properties were largely unaffected by the change in the topographic map. There was no difference in the receptive-field size of single tectal cells of lesioned and unlesioned animals. Stimulus velocity and stimulus size tuning functions remained the same. This raises the possibility that, rather than the expected increase in convergence of retinal ganglion cells (RGC) onto single collicular cells, single SC cells receive input from ganglion cells representing the same amount of retinal area as in unlesioned animals. The excess ganglion cells created by the partial target removal would then project elsewhere and/or reduce their arbor within the SC. Regardless of the mechanism, it is clear from our results that circuitry in the retinotectal system of the hamster can compensate for conditions of increased afferent availability and thus maintain receptive-field properties.

Tectal evoked potentials (TEPs) in response to sinusoidal gratings of different contrast, spatial and temporal frequency have been recorded from the tectal surface of the pigeon. Responses have been digitally filtered in order to isolate transient oscillatory (fast) potentials (50–150 Hz), transient slow potentials (1–50 Hz), and the steady-state second-harmonic component (16.6 Hz). Transient slow potentials, as well as the steady-state second-harmonic component, are band-pass spatially tuned with a maximum at 0.5 cycles/deg and attenuation at higher and lower spatial frequencies. The high spatial frequency cutoff is 4–5 cycles/deg. Both transient slow potentials and the steady-state second-harmonic component increase in amplitude as a function of log contrast and saturate at about 20% contrast. The contrast sensitivity, as determined by extrapolating TEP amplitude to 0 V is 0.1–0.2%. These characteristics of spatial-frequency selectivity and contrast sensitivity are similar to those reported for single tectal cells. Unlike slow potentials, oscillatory potentials are not band-pass spatially tuned. In addition, their contrast response function does not saturate at moderate contrast. These differences suggest that tectal evoked slow and fast potentials reflect the activity of different neuronal mechanisms.

This study was performed in order to establish whether selective depletion of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the pigeon optic tectum (TeO) induced by p-chloroamphetamine (p-CA) modified tectal evoked potentials (TEPs). TEPs in response to sinusoidal gratings of different contrast, spatial and temporal frequency were recorded in control pigeons and in pigeons intraperitoneally injected with p-CA (10 mg/kg; two administrations in consecutive days). TEPs of p-CA treated pigeons, as compared to those of control pigeons, were reduced in amplitude as a function of contrast, spatial and temporal frequency. In addition, TEPs of p-CA treated pigeons differed from those recorded in controls in their transfer characteristics of contrast and spatial frequency. In particular, TEPs of p-CA treated pigeons did not saturate at moderate contrast, unlike those of controls. Furthermore, the TEP spatial tuning in p-CA treated pigeons is broader than that in controls; it thus suggests a reduction of spatial-frequency selectivity. These findings indicate that a selective neurotoxin for serotonergic systems, such as p-CA, can serve as a useful denervation tool for the study of the serotonergic function in the pigeon TeO. In addition, selective changes of TEP properties suggest the possibility that serotonergic afferents play a modulatory role on the receptive-field characteristics of tectal neurons.

The tectum of Xenopus frogs receives input from both eyes. The contralateral eye's projection reaches the tectum directly, via the optic nerve, and the ipsilateral eye's projection reaches the tectum indirectly, via the nucleus isthmi. Under normal conditions, the topography of the ipsilateral map relayed from the nucleus isthmi is in register with the topography of the retinotectal map from the contralateral eye. During development, the process of aligning the two maps is complicated by the dramatic changes in binocular overlap of the two eyes' visual fields which take place during late tadpole and juvenile stages. The goal of this study is to determine the branching patterns of contralaterally projecting isthmotectal axons before, during, and after the period of rapid eye migration.

Isthmotectal axons were filled by anterograde transport of horseradish peroxidase (HRP) from the nucleus isthmi. The results show that crossed isthmotectal axons enter the entire extent of the tectum before binocular overlap begins to increase. Therefore, binocular overlap is not necessary for the initial isthmotectal projection to span the tectum. The density of isthmotectal branches rises dramatically at the same time that the eyes begin to shift. During the period when eye migration is most rapid, many isthmotectal axons form arbors which resemble adult arbors but which extend over greater proportions of the tectal surface.

The axons appear to be directed toward appropriate mediolateral positions as they enter the tectum. Their trajectories are roughly rostocaudal, with relatively little change along the mediolateral dimension. These data, when combined with available physiological data, suggest that mediolateral order is initially established by vision-independent mechanisms but can be altered by vision-dependent mechanisms. Rostrocaudal order becomes discernable only at the time when binocular visual cues become available and appears to be established primarily on the basis of the activity of the retinotectal and isthmotectal axons.

The sensitivity of neurons in area 17 of the cat's visual cortex to vernier offset was expressed as the percentage reduction in response caused by the introduction of a given offset into a bar stimulus moving across the receptive field. There was a wide variation in sensitivity: in some cells response could be halved by an offset equal to a fifth of receptive-field width (defined as twice the standard deviation of a Gaussian curve fitted to the response profile), while other cells showed no sensitivity. The highest absolute sensitivities of complex and simple cells were similar, although most cells with poor sensitivity were complex.

Sensitivity was largely unaffected by changes in stimulus velocity and stimulus length, although there was a tendency for sensitivity to increase with decreasing bar length.

Comparisons of orientation tuning curves with vernier tuning curves showed that the response to a vernier stimulus approximated the response to a single bar of the same overall length and an orientation equal to that of a line joining the midpoints of each bar. This was true for a wide range of sensitivity values.

Vernier sensitivity was correlated with a measure of length summation H, which is positive when there is net facilitation between the bars, and negative when there is net inhibition. Vernier sensitivity was highest in cells with large values of H, and least in cells where H was negative.

We examined a linear model of the simple cell receptive field which, together with a variable response threshold, was able to explain the correlation between vernier acuity and length summation. Although this model accounted qualitatively for many of our findings, the majority of simple cells had tuning curves that were sharper than the predicted ones. This suggests that there are nonlinearities in the behavior of many simple cells whose effect is to increase the sharpness of orientation tuning and consequently vernier sensitivity.

We have examined the distribution of preferred directions of motion for neurons in the middle temporal visual area (MT) of the macaque. We found a marked anisotropy favoring directions that are oriented away from the center of gaze. This anisotropy is present only among neurons with peripherally located receptive fields. This peripheral centrifugal directionality bias corresponds well to the biased distribution of motions characteristic of optic flow fields, which are generated by displacement of the visual world during forward locomotion. The bias may facilitate the processing of this common form of visual stimulation and could underlie previously observed perceptual anisotropies favoring centrifugal motion. We suggest that the bias could arise from exposure of modifiable cortical circuitry to a naturally occurring form of selective visual experience.

Cell suspensions of embryonic occipital cortex were transplanted into newborn rats with large unilateral visual cortex lesions. When the animals were adults, they were tested on a difficult visual discrimination, and subsequently their brains were analyzed for possible neurotrophic effects of the transplants on nonvisual cortical areas which normally form connections with the occipital cortex. Behaviorally, animals with lesions and transplants learn to discriminate between columns and rows of squares at a rate which is identical to normal rats while animals with lesions and no transplants are impaired. Volume and cell-density measures show that the transplants also rescue neurons in cortical area 8 that would normally degenerate following the cortical lesion. No such neurotrophic effect of the transplants is found in cortical area 24 or area 17 contralateral to the lesion. In rats with lesions and no transplants, there is a significant correlation between the amount of area 8 remaining after the lesion and trials to criterion on the columns-rows discrimination, a relationship that does not exist in transplant animals because of their normal learning curve and the consistent sparing of area 8. Injections of HRP into the visual cortex contralateral to the lesion result in variable numbers of labeled cells within the transplant. However, there is no consistent relationship between the number of transplant cells which project to the opposite hemisphere and learning of the discrimination. It is suggested that the learning deficit following the lesion is largely attentional and that the sparing of cortical area 8 (which in rats may include the analog of the frontal eye fields present in the primate cortex) contributes to the sparing of function.