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Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity.

We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These findings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional significance of these observations is discussed.

Animals↗

A time-based stereoscopic depth mechanism in the visual cortex.

We propose a new depth mechanism, operating in the visual cortex, which uses temporal as well as spatial cues. By varying the timing of input to the two eyes, and the position of stimuli on the two receptive fields, we show that both temporal and spatial disparities influence the binocular responses of single cortical cells.

Animals↗

Lateral interactions in visual cortex.

The findings presented in these studies have brought out different ideas concerning the mechanisms of processing in primary visual cortex than were held at the outset. Rather than thinking of receptive fields as being restricted in their extent, with the process of integration of the components of an image occurring at a much later stage along the visual pathway, we have shown that the integrative process is a progressive one, beginning in the primary visual cortex (or perhaps even earlier) and building up in a cascading series of converging and diverging connections. Rather than thinking of the filter characteristics of a cell as being fixed, it is apparent that they are dynamic and can be modified by the context in which features are presented. Finally, rather than a cortex with a functional architecture that is fixed after a critical period ending in infancy, we find that perturbing the system can lead to long-term topographical reorganization. Other examples of contextual interactions have been demonstrated in the submodalities of motion, where a cell's directional selectivity is modulated by the presence of movement in the surround (Allman et al. 1985; Tanaka et al. 1986; Gulyas et al. 1987; Orban et al. 1987). In the domain of color, the phenomenon of color constancy, reported for cells in visual area V4 (Zeki 1983), also requires lateral interactions in visual space, comparing the wavelength distribution of light coming from surfaces in different parts of the visual field. The influences presented in these studies, as in our own work in the domain of orientation, are modulatory. The long-term changes in cortical topography following removal of somatosensory input (Merzenich et al. 1984, 1988) or by retinal lesions suggest that with the appropriate manipulations the lateral interactions can be enhanced to the point of activating the postsynaptic cells. Although retinal lesions clearly represent an abnormal disruption of sensory input, they may nevertheless be representative of long-term reorganizations of neural networks occurring under normal circumstances, such as those required for memory.

Animals↗

Quantitative morphological effects of dark-rearing and light exposure on the synaptic connectivity of layer 4 in the rat visual cortex (area 17).

The quantitative effects of dark-rearing and light exposure on the ultrastructural characteristics of synapses and synaptic boutons in layer 4 of the rat visual cortex (area 17) have been investigated using stereological techniques. Two experimental groups (each containing 5 animals) were investigated-i) animals dark-reared upto weaning at 21 days post natum (21DPN) and then light exposed until 52DPN (Group 21/31), and ii) littermate animals totally dark-reared until 52DPN (Group 52dD). The results indicate a significantly higher mean density of synapses in the neuropil of layer 4 in group 21/31 (3.58 X 10(8).mm-3) compared with group 52dD (2.68 X 10(8).mm-3). Although the density per unit volume of synapses with identified asymmetrical synaptic membrane specialisations was not significantly different in group 21/31 than in group 52dD (but was significantly lower than animals reared normally), the density of synapses with identified symmetrical synaptic membrane specialisations was about 200% higher in group 21/31 versus group 52dD. However, significant differences were detected in the number of asymmetrical synapses established by single synaptic boutons in group 21/31 (1.21 +/- 0.11) compared with group 52dD (1.10 +/- 0.09). On the basis of the numbers of post-synaptic targets contacted by an individual synaptic bouton, a significantly higher density of synaptic boutons was found in group 21/31 (2.32 X 10(8).mm-3) compared with group 52dD (1.82 X 10(8).mm-3). Furthermore, planar quantitative data indicated significant intergroup differences in the ultrastructure of asymmetrical and symmetrical synaptic boutons. The results of this study provide evidence indicating marked structural alterations in the synaptic connectivity of layer 4 of the rat visual cortex following the light exposure of rats dark-reared upto weaning. Indeed visual deprivation severely affected the 'inhibitory' circuitry in the major thalamorecipient territory of the visual cortex.

Animal Husbandry↗

Ocular dominance plasticity restored by NA infusion to aplastic visual cortex of anesthetized and paralyzed kittens.

We studied the ocular dominance distribution in visual cortex of kittens which had been monocularly exposed to moving-pattern stimuli under anesthesia and paralysis. 1. We did not obtain any discernible changes in ocular dominance, confirming the previous reports that anesthesia and paralysis prevent ocular dominance plasticity from occurring. 2. The plasticity, however, was restored under the acute experimental condition by a cortical infusion of 1-noradrenaline (1-NA). In the 1-NA-infused visual cortex, the ocular dominance distribution was clearly shifted to the open eye after monocular exposure for about 20-24 h. 3. We also studied how quickly and to what extent the changes were induced when the duration of the combined treatment was varied. The results were: (i) the earliest change was observed in approximately 12 h with disappearance of binocular cells, (ii) the treatment was most effective after 20-24 h in inducing the shift of ocular dominance, and (iii) the treatment longer than 24 h (up to 45 h) did not necessarily enhance the shift, though the state of reduced binocularity was sustained throughout. 4. The effects of the cortical 1-NA infusion combined with monocular exposure became less with increasing the age of experimental animals, suggesting the presence of the "susceptible period" in the acute experiments. 5. The effects seemed to become smaller toward the end of a given recording session, suggesting that the restored plasticity wanes with time. The present results further support the idea that the direct activation of the NA system enhances cortical plasticity, in principle, independent of general conditions of experimental animals.

Aging↗

Effect of onset age of strabismus on the binocular responses of neurons in the monkey visual cortex.

PURPOSE: By 6 weeks of age, neurons in the monkey's primary visual cortex acquire qualitatively adult-like binocular response properties and behaviorally stereopsis emerges. In this study, it was determined whether the onset of strabismus has a more severe impact on cortical binocularity before or after this critical developmental age. METHODS: Infant monkeys were fit with a light-weight helmet which held a total of 27 diopters of base-in prisms in front of their two eyes for a fixed period of two weeks. For one group of infant monkeys, prism-rearing began at 2 weeks of age and for a second group, the onset was at 6 weeks of age. Immediately after the rearing period, i.e., at 4 weeks and 8 weeks of age, respectively, extracellular single-unit recording methods were used to determine the nature and severity of alterations in the binocular response properties of V1 neurons. Dichoptic sinewave gratings were used as visual stimuli. RESULTS: In comparison to normal age-matched infants, V1 neurons in both strabismic groups exhibited reductions in sensitivity to interocular spatial phase disparities (disparity sensitivity) and a higher prevalence of binocular inhibitory interactions (binocular suppression). However, the reduction in disparity sensitivity and the magnitude of binocular suppression were much greater in the late (6-8 weeks) than the early (2- 4 weeks) onset group. CONCLUSIONS: Discordant binocular signals due to brief periods of early strabismus have more serious effects on the development of binocular properties of V1 neurons if they occur shortly after rather than before the emergence of stereopsis (i.e., when the binocular connections are relatively more mature but the visual cortex still shows a high degree of plasticity).

Age of Onset↗

Extrastriate feedback to primary visual cortex in primates: a quantitative analysis of connectivity.

Knowledge-based or top-down influences on primary visual cortex (area V1) are believed to originate from information conveyed by extrastriate feedback axon connections. Understanding how this information is communicated to area V1 neurons relies in part on elucidating the quantitative as well as the qualitative nature of extrastriate pathway connectivity. A quantitative analysis of the connectivity based on anatomical data regarding the feedback pathway from extrastriate area V2 to area V1 in macaque monkey suggests (i) a total of around ten million or more area V2 axons project to area V1; (ii) the mean number of synaptic inputs from area V2 per upper-layer pyramidal cell in area V1 is less than 6% of all excitatory inputs; and (iii) the mean degree of convergence of area V2 afferents may be high, perhaps more than 100 afferent axons per cell. These results are consistent with empirical observations of the density of radial myelinated axons present in the upper layers in macaque area V1 and the proportion of excitatory extrastriate feedback synaptic inputs onto upper-layer neurons in rat visual cortex. Thus, in primate area V1, extrastriate feedback synapses onto upper-layer cells may, like geniculocortical afferent synapses onto layer IVC neurons, form only a small percentage of the total excitatory synaptic input.

Animals↗

Pre- and postnatal development of the primary visual cortex of the common marmoset. I. A changing space for synaptogenesis.

The primary visual cortex of Callithrix jacchus occupies a large portion of the occipital neocortex and can be safely delineated from fetal stages onwards. In 20 animals ranging in age from fetal to adult age the morphological development of area 17 was evaluated and compared with the growth of whole brain, skull, and head size. Cortical thickness, surface area, and volume of the area were determined in addition to predominant growth directions. The volume of area 17 approximately doubles between birth (241 mm3) and three months of age (506 mm3). This maximum value marks an overshoot in growth (volume: 180%, surface area: 150%, thickness: 122%), which is followed by a considerable reduction before adult values (100%) are reached. Although these values seem to indicate that the overall reduction in size is fairly isometric, growth and regression are locally anisometric. For example, layers II-IVc contribute disproportionately to the overshoot; thickening is less pronounced than tangential growth and follows a slightly different time course. These data suggest that the developing visual cortex represents a highly dynamic distribution space for the developing synaptic junctions which should be taken into account in studies on synaptogenesis. By comparison it is suggested that this growth dynamic is not restricted to area 17 but also occurs in some other parts of the cerebral cortex. In contrast, most subcortical brain regions apparently do not undergo overshoot growth. Structural changes of the skull compensate the overshoot in cortex growth, so that head size increases steadily.

Animals↗

Effect of visual experience on tubulin synthesis during a critical period of visual cortex development in the hooded rat.

1. In some species, restriction of visual experience in early life may affect normal functional development of visual cortical cells. The purpose of the present study was to determine if visual deprivation during post-natal development in the hooded rat also affects the production in brain cells of certain molecular components such as tubulin, that are needed for growth and maintenance of synapses and neurites. 2. Norwegian black hooded rats were reared under a variety of conditions of visual deprivation. At various stages of development the animals were killed and the rate of synthesis of tubulin in visual and motor cortex determined. Tritiated colchicine was used to assay tubulin and L-[14C]leucine injected into the brain ventricles 2 hr before death was used to measure rate of tubulin synthesis. 3. In rats reared in normal light there is a marked elevation in visual cortex tubulin synthesis that spans the period from eye-opening (13 days) until approximately 35 days. This elevation in tubulin synthesis is absent in animals reared in darkness from birth or deprived of pattern vision by eyelid suture. Also the effect of visual deprivation on tubulin synthesis was specifically confined to visual cortex and was not found for the motor cortex. Similarly, the incorporation of L-[14C]leucine into total protein in visual cortex was unaffected by dark rearing. Hence the stimulation of tubulin synthesis by visual experience in rat visual cortex is not attributable to a general non-specific stimulation of protein synthesis. 4. Rats that were dark-reared from birth and then exposed to a lighted environment for 24 hr during a certain critical period that extends from eye-opening (13 days) until approximately 35 days, displayed a significant increase in visual cortex tubulin rats that were brought into the light later than 35 days showed no significant increase in tubulin synthesis when compared with their continuously dark-rearer controls. 5. It is suggested that the number of synapses and cytoplasmic processes that a developing cell can maintain depends on the size of the tubulin pool available to that cell. Tubulin in brain only has a half-life of about 4 days, so when the level of tubulin drops this could result in competition between different synapses for the limited supply of tubulin needed for their maintenance, a factor which may contribute to the structural plasticity of the visual cortex during the critical period.

Aging↗

Retinotopic and nonretinotopic field potentials in cat visual cortex.

Two types of field potentials were identified in cat visual cortex using contrast reversal of oriented bar gratings: a short-latency fast-local component with a retinotopic organization similar to that seen with single-unit discharges at the same cortical site, and a slow, nonretinotopic component with a longer peak latency. The slow-distributed component had an extensive receptive field mapped by measuring the amplitude of binary kernels and showed strong inhibitory interactions within the receptive field. The peak latency of the slow-local component increased with distance from the retinotopic center, suggesting a possible conduction delay. Both components showed some orientation bias depending on the laminar location, but the bias could be independent of the orientation preferred by single units in the immediate vicinity. The present findings indicate that locally generated field potentials reflect cortical mechanisms for nonlinear integration over wide areas of the visual field.

Animals↗

A direct projection from area V1 to area V3A of rhesus monkey visual cortex.

Small cortical lesions were made in regions of the primary visual cortex (V1) representing different retinal eccentricities. It was found that, whereas all parts of V1 project to visual areas V2, V3 and the motion area of the superior temporal sulcus, only parts of V1 representing peripheral eccentricities (in excess of 30 degrees) project directly to visual area V3A.

Animals↗

Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation.

Two days of monocular deprivation (MD) of kittens during a critical period of development is known to produce a loss of visual responses in the primary visual cortex to stimulation of the nondeprived eye, and 7 days of deprivation results in retraction of axon branches and loss of presynaptic sites from deprived-eye geniculocortical arbors. The rapid loss of responsiveness to deprived-eye visual stimulation could be due to a decrease in intracortical excitatory input to deprived-eye ocular dominance columns (ODCs) relative to nondeprived-eye columns. Alternatively, deprived-eye visual responses could be suppressed by an increase in intracortical inhibition in deprived columns relative to nondeprived columns. We tested these hypotheses in critical period kittens by labeling ODCs in layer IV of primary visual cortex with injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into lamina A of the lateral geniculate nucleus (LGN). After either 2 or 7 days of MD, densities of intracortical excitatory presynaptic sites within deprived relative to nondeprived ODCs were estimated by measuring synaptic vesicle protein (SVP) immunoreactivity (IR). Because most of the synapses within layer IV of primary visual cortex are excitatory inputs from other cortical neurons, levels of SVP-IR provide an estimate of the amount of intracortical excitatory input. We also measured levels of immunoreactivity of the inhibitory presynaptic terminal marker glutamic acid decarboxylase (GAD)65 in deprived relative to nondeprived ODCs. Monocular deprivation (either 2 or 7 days) had no effect on the distributions of either SVP- or GAD65-IR in deprived and nondeprived columns. Therefore, the rapid loss of deprived-eye visual responsiveness following MD is due neither to a decrease in intracortical excitatory presynaptic sites nor to an increase in intracortical inhibitory presynaptic sites in layer IV of deprived-eye ODCs relative to nondeprived columns.

Animals↗

[Convergent properties of 3 types of visual cortex neurons recorded with various action potential amplitudes].

Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes of action potentials to photic, acoustic and electro-cutaneous stimuli were studied. It was shown that N1 neurones as differing from N3 were predominantly polymodal, often reacted with inhibitory responses and their background activity was characterized by random distribution of interstimuli intervals. Inputs for heteromodal stimuli were found to differ in N1 and N3 neurones. The results suggest existence of functional heterogeneity of neurones, recorded with different action potential amplitudes.

Action Potentials↗

Different types of signal coupling in the visual cortex related to neural mechanisms of associative processing and perception.

The hypothesis of object representation by synchronization in the visual cortex has been supported by our recent experiments in monkeys. They demonstrated local synchrony among gamma activities (30-90 Hz) and their perceptual modulation, according to the rules of figure-ground segregation. However, gamma-synchrony in primary visual cortex is restricted to few mm, challenging the synchronization hypothesis for larger cortical object representations. The restriction is due to randomly changing phase relations among locally synchronized patches which, however, form continuous waves of gamma-activity, traveling across object representations. The phase continuity of these waves may support coding of object continuity. Interactions across still larger distances, measured among cortical areas in human data, involve amplitude envelopes of gamma signals. Based on models with spiking neurons we discuss potentially underlying mechanisms. Most important for gamma synchronization are local facilitatory connections with distance-dependent delays. They also explain the occurrence of gamma waves and the restriction of gamma-synchrony. Fast local feedback inhibition generates gamma oscillations and supports local synchrony, while slow shunting inhibitory feedback supports figure-ground segregation. Finally, dispersion in inter-areal far projections destroys coherence of gamma signals, but preserves their amplitude modulations. In conclusion, we propose that the hypothesis of associative processing by gamma synchronization be extended to more general forms of signal coupling.

Action Potentials↗

Effects of visual deprivation on polyribosome aggregation in visual cortex of the cat.

Neurons in the visual cortex of 48 normal and visually deprived kittens and cats were examined electron microscopically for the presence of absence of polyribosomes in their perikaryal cytoplasm. In normal animals at most ages the ribosomes of cortical neurons were aggregated into polysomes, but during the second and third months of life -- a period corresponding approximately to the physiologically defined critical period -- variable numbers of cells were found which contained ribosomes only in the monomeric form. The affected cells were spiny stellate neurons in the fourth layer of the cortex. Even within the critical period, however, cells with dispersed ribosomes were not found in every animal examined.

Animals↗

Representation of color stimuli in awake macaque primary visual cortex.

We investigated the responses of single neurons in primary visual cortex (area V1) of awake monkeys to chromatic stimuli. Chromatic tuning properties, determined for homogeneous color patches presented on a neutral gray background, varied strongly between cells. The continuum of preferred chromaticities and tuning widths indicated a distributed representation of color signals in V1. When stimuli were presented on colored backgrounds, chromatic tuning was different in most neurons, and the changes in tuning were consistent with some degree of sensitivity of the neurons to the chromatic contrast between stimulus and background. Quantitatively, the average response changes matched the magnitudes of color induction effects measured in human subjects under corresponding stimulus conditions.

Animals↗

Oscillatory activity is not evident in the primate temporal visual cortex with static stimuli.

It has been suggested in studies in the visual system of anaesthetized cats that oscillatory activity with a frequency of 40-60 Hz occurs during the presentation of moving visual stimuli and reflects a synchronization process between neurons that could implement the binding together of related neurons into different sets. We found no evidence for such oscillations in the inferior temporal visual cortex and related areas of awake macaques fixating effective static visual stimuli, which for the neurons analysed were faces. We put forward the possibility that temporal synchronization between neurons to implement binding may not be generally used in the visual system as a solution to the binding problem, at least when static objects are being processed and recognised in higher parts of the visual system.

Animals↗

A quantitative study of the classification and stability of ocular dominance in the cat's visual cortex.

We recorded from single cells in the cat's visual cortex to quantitatively evaluate (1) the reliability of subjective assessments of ocular dominance (101 cells) and (2) the stability of ocular dominance over time (25 cells). We found that the correlation between subjective and objective measures of this variable was poorer than expected, and was worst for cells with low overall response strengths. This result appears to reflect variability in the subjective assessment procedure. For the second part of the study, we recorded from single cortical cells of 5-week-old kittens, and made repeated objective measurements of ocular dominance over time. Twenty-four of the twenty-five cells examined were quite stable in ocular dominance for periods so long as 8 h. One unit was encountered which showed substantial progressive shifts in ocular dominance over time.

Animals↗