We analyzed the immunohistochemical distribution of the two calcium-binding proteins, parvalbumin (PV) and calbindin D-28k (CB), in the primary visual cortex and lateral dorsal geniculate nucleus (dLGN) of monocularly enucleated macaque monkeys (Macaca fascicularis and Macaca nemestrind) in order to determine how the expression of PV and CB is affected by functional inactivity. The monkeys survived 1–17 weeks after monocular enucleation. The distribution pattern of each of the proteins was examined immunocytochemically using monoclonal antibodies and compared with that of the metabolic marker cytochrome oxidase (CO). We recorded manually the number of immunostained neurons and estimated the concentration of immunoreactive staining product using a computerized image-acquisition system. Our results indicate a decrease of approximately 30% in the labeling of PV-immunoreactive (ir) neuropil particularly in those layers of denervated ocular-dominance columns receiving the geniculocortical input. There was no change in the number of PV-ir neurons in any compartment irrespective of the enucleation interval. For CB-ir, we found a 20% decrease in the neuropil labeling in layer 2/3 of the denervated ocular-dominance columns. In addition, a subset of pyramidal CB-ir neurons in layers 2 and 4B, which are weakly stained in control animals, showed decreased labeling. In the dLGN of enucleated animals, PV-ir and CB-ir were decreased only in the neuropil of the denervated layers.

From these results, we conclude that cortical interneurons and geniculate projection neurons still express PV and CB in their cell bodies after disruption of the direct functional input from one eye. The only distinct decrease of PV and CB expression is seen in axon terminals from retinal ganglion cells in the dLGN, and in the axons and terminals of both geniculocortical projection cells and cortical interneurons in the cerebral cortex.

Tritiated proline and leucine were injected into areas 17 and 18 of intact cats and into the medial bank of the lateral suprasylvian (LS) cortex of intact cats and cats from which areas 17 and 18 had been removed on postnatal day 1 (P1), P28, or in adulthood (A). The density of label transported to the superior colliculus was quantified using image-analysis equipment. The results from the intact cats confirmed previous reports that areas 17 and 18 project most heavily to stratum zonale (SZ) and stratum griseum superficiale (SGS) and LS cortex projects most heavily to stratum opticum (SO) of the superior colliculus. However, in cats with lesions of areas 17 and 18, the projections from LS cortex showed an age-dependent reorganization. LS projections to SGS and SZ were enhanced following ablation of areas 17 and 18 on P1, and projections to SGS were enhanced following an ablation on P28. The pattern of LS-collicular projection following ablations incurred in adulthood was indistinguishable from the pattern presented by intact cats. This study demonstrates that the LS corticocollicular projection expands in SGS and possibly substitutes for inputs eliminated by the removal of areas 17 and 18 from the immature brain. This enhanced pathway may contribute to compensatory neuronal changes and to spared behaviors that accompany damage of immature cortex.

Four experiments were performed to assess the effects of ON channel blockade with the glutamate analog 2-amino-4-phosphonobutyrate (APB) on brightness and contrast perception in monkeys. In Experiment 1, we demonstrate that stimuli brighter than background (incremental stimuli) appear less bright following ON channel blockade. This decrease in brightness is not enough to account for the previously observed threshold increase for detection of incremental stimuli following APB administration (Schiller et al., 1986; Dolan & Schiller, 1989). Experiment 2 examines the role of the ON and OFF channels in the interaction between local contrast and apparent brightness. The phenomenon of simultaneous contrast was examined under normal conditions and following APB administration. We find that even following ON channel blockade, the brightness of a stimulus is determined primarily by its contrast with its immediate background. This indicates that the lateral processes involved in simultaneous contrast can operate even when one channel has been compromised. In Experiment 3, we examined the role of the ON channel in detection of stimuli that appear by virtue of changes in background vs. foreground luminance. We find that the ON channel selectively conveys information pertaining not only to the temporal nature that defines the stimulus as incremental but also to the spatial features that define it as incremental. In Experiment 4, we test the hypothesis that incremental and decremental temporal luminance ramps are differentially processed by the ON and OFF channels to a higher degree than are step-luminance changes. We find that the detection of incremental ramps is no more affected than is the detection of incremental steps following APB administration.

The molecules which control the patterns of cell division, growth, and precise interconnections characteristic of the central nervous system still remain largely unidentified. The protein platelet-derived growth factor (PDGF) has been shown to mediate interactions among glial cells in vitro. More recent evidence has indicated that PDGF may also be involved in controlling communication between neurons and glial cells and among neurons. The presence of receptors for PDGF on neurons of the developing nervous system is an essential piece of evidence in this chain of events. Ganglion cells are labeled with antibodies to PDGF receptor only during the period of active process outgrowth. These findings suggest that PDGF is used as a mediator of intercellular signaling during neuronal development.

Enzymatic treatments that facilitated whole-cell electrophysiological recordings were used on Limulus ventral photoreceptor cells. Ventral optic nerves were treated with either collagenase or collagenase, papain, and trypsin. Either treatment greatly increased the ease of making whole-cell recordings of transmembrane potentials. Light responses obtained from enzyme-treated photoreceptor cells were nearly identical to results obtained without enzyme treatment and compared favorably to in vivo recordings of light responses from the compound lateral eye. Enzyme-treated cells also responded to applied octopamine, as do untreated cells, with an increased phosphorylation of a 122-kD protein. This suggests that the external receptors and internal biochemical machinery required for at least one second-messenger cascade are present after enzyme treatment. The morphological integrity of enzyme-treated photoreceptor cells was examined with light microscopy as well as with scanning and transmission electron microscopy. In general, we found that each enzyme treatment greatly reduced the integrity of the layers of glial cells that surround the photoreceptor cells thereby making these cells easily accessible for whole-cell recordings of transmembrane potentials. The morphology of the rhabdomere was normal after enzymatic degradation of the adjacent glial covering.

The effect of light adaptation on the period of photocurrent saturation induced by a bright stimulating flash was examined in rod photoreceptors of the larval-stage tiger salamander (Ambystoma tigrinum). Using suction electrodes, photocurrent responses to brief flashes were recorded from single, isolated rods in the presence and absence of steady background illumination. Background light decreased the saturation period (T) measured at fixed flash intensity (fixed If) and in this respect light-adapted the saturating response. Effects of the background on responses to weak (i.e. subsaturating) and bright flashes were compared with changes in a parameter, where ΔT is the decrease in saturation period, and where TR* is the slope of the line that relates T and ln If in a given state of adaptation. Dark- and light-adapted responses to flash intensities and , respectively, exhibited similar absolute peak photocurrent and falling-phase kinetics when and satisfied the relation, , where Ib is the background intensity. It is argued that ψ approximates the relative PDE*/R* gain of transduction, i.e. the relative peak level of activated cGMP phosphodiesterase (PDE*) produced by a given, small amount of photoactivated visual pigment (R*). Interpreted on this view, the results imply that light adaptation derives largely from a decrease in PDE*/R* gain, rather than from the stimulation of guanylate cyclase activity. The data are consistent with the possibility that modulation of the lifetime of PDE* underlies the background dependence of ψ.

Two cDNA clones for nicotinic acetylcholine receptor (nAChR) subunits sensitive to α-bungarotoxin (α-Bgt) have been isolated, the so-called α-Bgt binding proteins α1 (or α7 nAChR subunit) and α2 (or α8 nAChR subunit). Immunohistochemical experiments have shown that both α7 and α8 subunits, as well as subunits insensitive to α-Bgt (β2 and α3), are present in amacrine and ganglion cells of the chick retina. However, only the α8 subunit was observed in presumptive bipolar cells. The present study investigated in detail the pattern of distribution of the bipolar cells containing the α8 nAChR subunit and its relation to the pattern of distribution of bipolar cells immunoreactive to protein kinase C (PKC). Presumptive α8-and PKC-like immunoreactive (α8-LI and PKC-LI) bipolar cells were observed sending their dendrites to the outer plexiform layers and their axons to the inner plexiform layer. Where as α8-LI bipolar cells corresponded to 40–53% of the whole population of bipolar cells, PKC-LI bipolar cells represented only 6–8% of the same population. The soma sizes of the α8-LI bipolar cells were slightly smaller (mean ± s.d.; 4.9 ± 0.8 μm) than the soma sizes of the PKC-LI bipolar cells (5.4 ± 0.9 μm). Double-labeling experiments indicated that probably all PKC-LI bipolar cells also contain α8-LI. This indicates that two distinct groups of cholinoceptive bipolar cells exist in the chick retina, one that contains PKC-LI, and another one that does not.

To characterize the postnatal development of geniculocortical axon arbor morphology in owl monkeys at a series of ages from birth to adulthood, individual arbors were bulk-filled with HRP in brain slice preparations and were reconstructed from serial sections. At all ages, cortical layers and sublayers were obvious. Presumed M or magnocellular arbors were largely confined to layer IVα, but they also extended into layer IIIc (IVB of Brodmann, 1909); presumed P or parvocellular arbors were almost exclusively confined to layer IVβ. Other axons that may reflect feedback projections from MT terminated in layer IIIc. Overall, M axon arbors increased in size and complexity from birth to adulthood with mean surface-view arbor areas ranging from 0.08 ± 0.01 mm2 in newborns to 0.24 ± 0.02 mm2 in adults. The developing P arbor areas were, on average, as large or larger than adult (newborn = 0.07 ± 0.01 mm2, adult = 0.047 ± 0.01 mm2; n.s.) but the arbors were somewhat less complex. Since the brain and area 17 increase in size postnatally, the proportion of area 17 subserved by each P arbor would decrease in postnatal development. Terminal boutons with immature features were evident in both M and P populations at all developmental ages. The results indicate that, while both LGN axon types in monkeys undergo morphological changes postnatally, M arbors appear to mature by increasing arbor size and terminal branching complexity, whereas P arbors increase in complexity but not in size. These distinct programs of axon arbor development suggest that the periods of susceptibility of geniculocortical axon arbors to postnatal influences of the environment, and the types of plastic responses they potentially exhibit, are class-specific.

Following bright flashes, rod photoreceptors exhibit a period of photocurrent saturation that increases linearly with the logarithm of flash intensity. In a recent report, Pepperberg et al. (1992) presented evidence that the slope of the function relating the saturation period (T) to the natural logarithm of flash intensity (In If) represents the exponential lifetime (τ) of photoactivated visual pigment: τ = ΔT/Δ[ln If]. In salamander rods, 11 -cis 9-desmethylretinal combines with opsin to form 9-desmethyl rhodopsin. Dim flash responses mediated by this analogue visual pigment exhibited slow recovery kinetics relative to those of native pigment (Corson et al., 1991). This observation raises the hypothesis that the physiological lifetime of photoactivated 9-desmethyl rhodopsin is substantially longer than that of native visual pigment. To test this hypothesis, we have examined the relation between the period of photocurrent saturation and flash intensity in salamander rods containing a mixture of the two pigments. Brief stimuli at two widely separated wavelengths (440 and 640 nm) elicited saturating photocurrent responses that were preferentially mediated by 9-desmethyl rhodopsin or residual native pigment, respectively. Plots of T vs. In If revealed a linear increase in the period of response saturation over a large range of saturating intensities at both wavelengths. However, the slope of the relation between T and In If with 440-nm flashes was more than twice as large (4.1 ± 0.5 s, n = 5) as that measured with 640-nm flashes (1.7 ± 0.4 s). For rods subjected only to bleaching of the native pigment, or to bleaching and resensitization with 11-cis retinal, the slope of the relation between T and In If remained independent of wavelength and indistinguishable from that of native pigment in unbleached cells. The data provide support for the hypothesis that the slope parameter τ represents the lifetime of photoactivated pigment, and specifically suggest that the lifetime of photoactivated 9-desmethyl rhodopsin is abnormally long.

Thresholds for psychophysically opposite stimuli—light and dark, or equiluminous red and green, or equiluminous blue and yellow—are usually nearly equal. This color threshold symmetry is sometimes violated in subjects who have optic nerve hypoplasia, a congenital loss of retinal ganglion cells. We describe a subject who has optic nerve hypoplasia, who exhibits large red-green and blue-yellow detection threshold asymmetries for equiluminous spots. Temporal and spatial integration for equiluminous red and green test spots also differed from normal; static perimetric thresholds for equiluminous green, blue, and yellow (but not red) spots lacked the normal “V” shaped minimum at the fovea. These asymmetries may relate to a developmental paucity of some ganglion cell subtypes. Optic nerve hypoplasia may allow the contributions to detection made by individual ganglion cell subtypes to be isolated psychophysically, in analogy to the study of cone spectral sensitivity in dichromats.

Steady discharges were collected from ganglion cells of the magnocellular (MC) and parvocellular (PC) pathways of the macaque while their receptive fields were uniformly illuminated with a 4.7-deg steady yellow light of photopic illuminance. The mean rates, coefficients of variation, interval distributions, serial correlation coefficients, and power spectra of these discharges were determined. The results presented permit one to estimate the noise power in the discharges of macaque ganglion cells and hence determine how visual signals of different amplitudes will be affected by the noise resident in their discharges.

Although there was some small serial correlation in the discharges of both MC- and PC-pathway cells, their discharges can be considered to result from renewal processes with reasonable accuracy. As with the discharges of cat ganglion cells, macaque ganglion cell discharges can be considered to have approximately gamma-distributed intervals. Steady discharges of MC- and PC-pathway cells show considerable overlap in their statistics, although small but significant differences are present.

Inferior temporal (IT) cortex is a “high-order” region of extrastriate visual cortex important for visual form perception and recognition in adult primates. The pattern of cortical afferents from both ipsilateral and contralateral hemispheres to anterior IT cortex was determined in infant macaque monkeys 7–18 weeks of age following injections of wheat-germ agglutinin-HRP. Within the ipsilateral hemisphere, the locations and laminar distribution of labeled cells were similar to those observed after comparable injections in adult monkeys. Specifically, ipsilateral afferents derived from visual areas V4, TEO, anterior and posterior IT, and STP, from parahippocampal, perirhinal, and parietal zones, and from several anterior zones including lateral and ventral frontal cortex, the insula, and cingulate cortex. Within the contralateral hemisphere, we observed labeled cells in homotopic regions of IT and in parahippocampal and perirhinal areas, as has been reported for adult monkeys. However, we also identified additional contralateral regions not previously known to provide input to anterior IT, including lateral and ventral frontal cortex, cingulate cortex, and STP. Overall, the strongest and most widespread projections from outside the temporal lobe were found in the youngest monkey, suggesting that some of these projections may represent transient circuitry necessary for the development of complex visual response properties in anterior IT.

The neurotransmitter used by horizontal cells in mammals has not been identified. GABA has been the leading candidate, but doubt has remained because of failure to clearly demonstrate the GABA synthetic enzyme, glutamic acid decarboxylase (GAD) in these cells. Because GAD was recently shown to exist as two isoforms, 65 kDa and 67 kDa, we considered whether there might be a mismatch between the forms of GAD expressed in horizontal cells and the probes used to detect it. Accordingly, we stained sections of mammalian retina with antibodies specific for each isoform. Cat horizontal cells of both types (A and B) were immunoreactive for GAD67 but negative for GAD65; monkey horizontal cells of both types (H1 and H11) were positive for GAD65 and negative for GAD67. The findings reconcile previous, apparently conflicting, observations and strengthen considerably the hypothesis that mammalian horizontal cells are GABAergic.

To determine whether central communication of retinal signals is necessary for the development of an experimentally induced myopia, tree shrews were exposed to monocular deprivation (MD) while the action potentials of retinal cells in the deprived eye were blocked with intravitreally injected tetrodotoxin (TTX-MD animals). TTX injections (0.6 μ 3 μL) and MD began about 15 days after eye opening, at the start of the susceptible period for the development of lid-suture myopia. Six injections were given, one every second day to produce 12 days of MD and TTX-blockade. Control TTX animals (TTX-open) received TTX in one eye, but not MD, on the same injection schedule and were always found to be behaviorally unresponsive to visual stimuli through the injected eye indicating that TTX blocked central communication of action potentials. Other control animals received intravitreally injected saline in either an open eye (saline-open), or an MD eye (saline-MD). A sham-injected group (sham-inj-MD) received MD and all anesthetic and surgical manipulations except for penetration of the sclera. In all groups, one eye in each animal was an untreated control.

Two effects were found. All MD groups, including the TTX-MD animals, developed a significant vitreous chamber elongation in the deprived eye, indicating that an experimental myopia developed despite ganglion cell blockade. Thus, retinal mechanisms in tree shrew can detect the presence of a degraded visual image and produce an experimental myopia that does not depend on the receipt of visual messages by central neural structures. In addition, eyes in which the sclera was punctured had smaller vitreous chamber depths than comparable uninjected eyes, indicating that puncturing the sclera reduced the normal elongation. These data suggest that forces within the eye normally contribute to its expansion and may be resisted by the choroid and/or the sclera.

Many studies of visual neurons make use of stimuli that are sinusoidally modulated in time, and take as the response the fundamental Fourier component of the firing. This is a study of the variability of the fundamental sinusoidal components.

A theoretical analysis shows that the variance of sinusoidal components should be nearly independent of their amplitudes; this is expected despite the observation that variance of firing rate increases with increasing firing rate. However, this result applies only to the variance of the complex amplitude, defined as the complex Fourier amplitude in response to each stimulus cycle. This variance is called the complex variance. The variance of the scalar amplitude, which is simply the amplitude in response to each stimulus cycle disregarding phase (scalar variance) is expected to shrink by a factor of up to 2⅓ as the response magnitude approaches zero.

If the relationship between variance of rate and rate is linear, complex variance should be independent of amplitude. If the relationship between variance of rate and rate is characterized by a compressive nonlinearity (as has been observed), the complex variance should very slightly decrease with increased amplitude, despite the main trend of increased variance of rate with increased rate.

Data from cat ganglion cells stimulated with sinusoidally modulated lights of various contrasts agree with the theory, although some individual cases show trends that may be indicative of nonlinearity in the relationship between variance of rate and rate.

In addition to a modulatory function, somatostatin (SS) is likely to exert a morphogenetic and/or trophic role in the developing nervous system. In this study, a mouse monoclonal antibody directed to SS was used to investigate the posthatching development of SS-immunoreactivity (SS-ir) in the pigeon retina to provide a basis for a better understanding of the role of this peptide in retinal maturation. In the adult, SS-ir was observed in amacrine cells located in the inner nuclear layer (INL) of the entire retina. Two cell types were recognized according to their morphology. They showed a differential density distribution. Cell type indicated as “adult 1” (AD1) was characterized by pear-shaped cell bodies with single primary processes directed to the inner plexiform layer (IPL) and was mostly present in the red field. In contrast, cell type indicated as “adult 2” (AD2) was characterized by round-shaped somata with 1–3 primary processes and was highly represented in the fovea and the dorsal periphery. Posthatching maturation of the pigeon retina was characterized by drastic changes in the pattern of SS-ir. Over the first days posthatching, SS-ir was observed in sparsely distributed somata mostly located in the ganglion cell layer (GCL). This cell type indicated as “hatch” (H) was characterized by dense granular staining and became extremely rare at 7 days. Over the same period, growing SS-positive axons displaying enlarged growth cones were found in the optic tract (TrO). These observations suggest the possibility that ganglion cells transiently expressing SS are present at early stages of posthatching development. Of the two types of SS-containing cells observed in the adult, the first to be recognized morphologically was cell type AD1 which appeared at 2 days after hatching in the INL. These cells were virtually adult-like in morphology by 7 days. In contrast, cell type AD2 was not apparent until 7 days posthatching. The density (defined as number of cells/mm2 of retinal tissue) and the total number of SS-containing cells changed during posthatching maturation. In particular, the adult number of cell type AD1 was reached at about 10 days, while the number of cell type AD2 was reached at about 3 weeks posthatching. At this stage, both cell types also displayed their mature density distribution. The present findings suggest a temporal relationship between the maturation of SS-ir and developmental events which include the onset of light-driven activity and the maturation of retinal acuity. Our results also demonstrate significant differences in the pattern of SS-ir between the avian and the mammalian retina and suggest that SS-containing neurons represent important intraretinal association neurons in the retina of birds.

Recent results indicate that astrocytic β-adrenergic receptors (βAR) participate in noradrenergic modulation of synaptic activity. In this study, we sought to examine whether neural activity can, in turn, regulate astrocytic βAR. To address this question, an antiserum that recognizes β-adrenergic receptors (βAR) specifically in astrocytes was used to assess the distribution of the receptors across ocular dominance columns in VI of two monocular and four visually intact adult monkeys. Cytochrome oxidase histochemistry (CO) was used to identify the position of the cortical laminae and of the ocular dominance columns receiving visual inputs from the intact and enucleated eyes. This stain revealed the expected pattern within V1 of monocular monkeys–i.e. darker and lighter bands of equal widths (ca. 500μm) spanning laminae 4–6, each associated with larger and smaller blobs, respectively, in lamina 2/3;. Alignment of CO sections with adjacent sections stained for astrocytic βAR by the immunoperoxidase method revealed intense βAR-like immunoreactivity (βAR-li) in the superficial laminae, a slightly weaker staining in the infragranular laminae and weakest staining in lamina 4C. Within lamina 4C., a prominent striped pattern was evident. The darker bands of the stripe closely matched widths and positions of the lighter CO columns associated with the enucleated eye. On the other hand, immunocytochemical staining for the astrocytic intermediate filament protein, GFAP, within V1 of monocular monkeys revealed no inter-columnar difference in the density of astrocytic cell bodies or processes. Nissl stain also revealed no overt inter-columnar differences in cell density. V1 of visually intact monkeys exhibited a similar laminar distribution pattern of βAR-li and of CO. Within lamina 4C., βAR-li was uniformly faint and CO staining was uniformly intense. This suggests that the striped pattern of βAR-li seen in lamina 4C of monocular monkeys results from elevation of the βAR-antigen within the inactive columns. The results indicate that astrocytic βAR density is regulated by local neural activity. The mechanisms regulating βAR density are likely to be independent of those regulating glial cell proliferation or GFAP synthesis. In vitro experimental results of others suggest that elevation of astrocytic βAR may be a mechanism compensating for chronic neural inactivity, since the coincident release of noradrenaline with visual stimulation would elevate neuropil excitability via the astrocytic mechanism of (1) decreasing the uptake of neuronally released L-glutamate; (2) increasing GABA uptake; and (3) stimulating glycogenolysis. Alternatively, the changes in βAR-li may reflect an up-regulation of the receptors within inactive columns due to reduced levels of noradrenaline release.