The development of lateral inhibitory interactions in the infant visual system, as reflected by the visual-evoked potential (VEP), was studied using a radial, asymmetrical windmill-dartboard stimulus. This contrast-reversing stimulus generates VEP responses with a strong fundamental frequency component and an attenuated second harmonic component (relative to that obtained using a symmetrical stimulus). These two harmonic components reflect distinct phenomena, and appear to be the result of short-range (the fundamental) and long-range (attenuated second harmonic) lateral inhibitory interactions elicited by differential luminance-modulation of contiguous spatial regions. We studied the development of the short-and long-range interactions at 100% and 30% contrast in human infants using both VEP amplitude and phase measures. Attenuation of the second harmonic (long-range interactions) was adult-like by 8 weeks of age while the strength of the fundamental (short-range interactions) was adult-like by 20 weeks suggesting a differential development of long-range and short-range interactions. In contrast, corresponding phase data indicated significant immaturities at 20 weeks of age for both the short-and long-range components.

Using suction electrodes, photocurrent responses to 100-ms saturating flashes were recorded from isolated retinal rods of the larval-stage tiger salamander (Ambystoma tigrinum). The delay period (Te) that preceded recovery of the dark current by a criterion amount (3 pA) was analyzed in relation to the flash intensity (If), and to the corresponding fractional bleach (R*0/Rtot) of the visual pigment; R*0/Rtot was compared with R*s/Rtot the fractional bleach at which the peak level of activated transducin approaches saturation. Over an approximately 8 In unit range of If that included the predicted value of R*s/Rtot, Te increased linearly with In If. Within the linear range, the slope of the function yielded an apparent exponential time constant (TC) of 1.7 ± 0.2 s (mean ± S.D.). Background light reduced the value of Tc measured at a given flash intensity but preserved a range over which Tc increased linearly with In If; the linear-range slope was similar to that measured in the absence of background light. The intensity dependence of Tc resembles that of a delay (Td) seen in light-scattering experiments on bovine retinas, which describes the period of essentially complete activation of transducin following a bright flash; the slope of the function relating Td and In flash intensity is thought to reflect the lifetime of photoactivated visual pigment (R*) (Pepperberg et al., 1988; Kahlert et al., 1990). The present data suggest that the electrophysiological delay has a similar basis in the deactivation kinetics of R*, and that Tc represents TR* the lifetime of R* in the phototransduction process. The results furthermore suggest a preservation of the “dark-adapted” value of TR* within the investigated range of background intensity.

We examined inward rectification in Limulus ventral photoreceptors using the two-microelectrode voltage clamp. Hyperpolarization in the dark induced an inward current whose magnitude was distinctly dependent on extracellular K+ concentration, [K+0]. The [K+0] dependence resembled the characteristic [K+0] dependence of other inward rectifiers. The inward current was not dependent on extracellular Ca2+ or Na+, and it was unaffected by intracellular injection of Cl−. The hyperpolarization induced currents had two phases, an early nearly instantaneous phase and a slowly developing late phase. The currents were sensitive to extracellular barium and cesium. In voltage-pulse experiments, the magnitudes of the inwardly rectifying currents were variable from cell to cell, with some cells exhibiting negligible inward currents. Large hyperpolarizations (to membrane potentials more negative than about – 140 mV) caused unstable inward current recordings, irreversible desensitization, and irreversible elevation of intracellular Ca2+ concentration. The inward rectifier provides negative feedback by tending to depolarize the cell (with inward current) in response to hyperpolarization. We suggest that the inward rectifier reduces the amount of hyperpolarization that would otherwise be generated by electrogenic processes. This feature would restrict the dynamic voltage range of the photoreceptors at very hyperpolarized potentials.

Foveal dark adaptation in 58 subjects and photopigment regeneration in 60 subjects from 10–78 years of age exhibit parallel slowing of recovery rate with increasing age, with significant correlation of the two functions among individuals. The data are suggestive of an initial slight decline in rate before age 50, followed by a greater decline occuring at different ages in different ages in different individuals. Longitudinal data for one subject from age 40–65 show an increase in pigment regeneration time constant consistent with this idea. Foveal sensitivity and photopigment density both decrease with increasing age and are significantly correlated among individuals, although sensitivity declines more with age than does photopigment density. In contrast to earlier proposals based upon the Rushton-Dowling equation, we found no universal constant of proportionality to relate log relative threshold to photopigment within our population.

Second messengers are involved in a number of cellular responses to a variety of stimuli. Diffusion of these second messengers likely will determine the speed and efficiency of such responses. Localization, particularly in large cells, would enhance the efficiency of such transduction systems by restricting the volume in which this diffusion takes place and thereby limiting the diffusion of soluble messengers. Phototransduction in Limulus ventral photoreceptors involves second-messenger systems; the volume of this cell is quite large, but the effect of a single photoexcited rhodopsin molecule is exerted over light-dependent channels localized within a very small area of the plasma membrane. In order to investigate localization of phototransduction in these photoreceptors, we have compared the light responses of small vesicles (photoballs) excised from these cells with those of the intact photoreceptors. We found that the basic kinetics of excitation and adaptation of the photoballs are essentially identical to those of the intact cell. This indicates that all of the necessary machinery for phototransduction is present and intact in the photoball and that any diffusion of second messengers that affect the normal light response of the cell must occur within a region at least as small as our photoballs (on the order of 1 μm3).

The recent isolation of at least five different cDNAs encoding functional subunits of glutamate receptors (GluR1 to GluR5) has revealed a diversity whose function is not understood. To learn more about how these different receptor subunits are used in the brain, we undertook an in situ hybridization study of the retina to define how the different glutamate receptor genes are expressed. We chose the retina because the glutamate sensitivities of its different cell types have been characterized, and these different neurons reside in different laminae.

Hybridization of [35S]UTP-labeled cRNA probes with transverse sections and freshly dissociated cells reveals that all five receptor subunits are expressed in the retina. Hybridization signal is detected in different, but overlapping, sets of cells in the retina. GluR1, GluR2, and GluR5 are expressed by many somata, and GluR4 by a few, in the outer third of the inner nuclear layer, where the horizontal cells reside. Transcripts for GluR1, GluR2, and GluR5 are found in the somata within the middle third of the inner nuclear layer, which is where the bipolar cell somata are located, and GluR2 probes label freshly dissociated rod bipolar cells. All of the probes produce labeling over the cells at the inner edge of the inner nuclear layer, which are probably amacrine cells, as well as over the cell bodies in the ganglion cell layer.

Dry autoradiography was used to determine the distribution of GABAA binding sites in tiger salamander retina. High-affinity binding of [3H]-flunitrazepam ([3H]-FNZ) was used to localize benzodiazepine receptors (BZR) and [3H]-muscimol was used to localize the GABAA recognition site. Specific [3H]-FNZ binding was present only in the inner retina, primarily in the inner plexiform layer (IPL). Co-incubation with GABA enhanced [3H]-FNZ binding by 20–50%. [3H]-muscimol binding was found throughout the IPL and in the outer plexiform layer (OPL). Mouse monoclonal antibodies 62–3G1 and BD-17, that recognize the GABAAβ2, β3 polypeptides, and BD-24, that recognizes the GABAA α1, polypeptide, did not label either the OPL or IPL, despite numerous variations in the fixation and immunoprocessing methods. GABAA receptor location, as revealed by [3H]-muscimol binding, matches the distribution of presumed GABAergic terminals in the OPL and IPL. We suggest that there are at least two subtypes of GABAA receptor in the tiger salamander retina: one type is present only in the inner retina, primarily in the IPL and is functionally coupled to BZRs; the other type is located in the OPL and is not coupled to the BZRs. Furthermore, GABAA receptors in the tiger salamander retina appear to be of a different epitope than GABAA receptors in numerous other preparations that are recognized by mAbs 62–3G1, BD-17, and BD-24.

Contrast sensitivity is a useful measure of the ability of an observer to distinguish contrast signals from noise. Although usually applied to human observers, contrast sensitivity can also be defined operationally for individual visual neurons. In a model linear neuron consisting of a filter and noise source, this operational measure is a function of filter gain, noise power spectrum, signal duration, and a performance criterion. This definition allows one to relate the sensitivities of linear neurons at different levels in the visual pathway. Mathematical formulae describing these relationships are derived, and the general model is applied to the specific problem of relating the sensitivities of parvocellular LGN neurons and cortical simple cells in the primate.

Gap junction (GJ) endocytosis appears to be part of a cycle of GJ renewal in horizontal cells of the teleost fish retina. At least three stages of GJ endocytosis in these neurons have been identified using conventional electron microscopy (EM): invagination of GJ membranes (GJ blebs); free GJ vesicles; and GJ vesicle fusion with mature lysosomes (Vaughan & Lasater, 1990a). In the present study, EM-level acid phosphatase (AP) histochemistry of white bass retina was used to determine at what stage enzymatic degradation of endocytosed GJs begins. Electron-dense AP reaction product was observed within the trans face of the Golgi apparatus, mature lysosomes, and occasional, internal GJ vesicles. In contrast, GJ blebs, peripheral GJ vesicles, and most internal GJ vesicles lacked AP reaction product. These results support the idea that at least some of the GJ vesicles observed within these retinal neurons arise from endocytosis, are on a degradative pathway, and can be termed GJ “endosomes.” Furthermore, GJ vesicles appear to be initially free of AP, but some later acquire it (presumably from transport vesicles bearing degradative enzymes). It is still unclear whether our previous report of GJ vesicle fusion with mature lysosomes is a subsequent step in GJ degradation or part of a different degradative pathway altogether.