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Effect of the richness of the environment on the cat visual cortex.

In a recent study of the cat visual cortex, it was shown that there are interindividual differences in the numerical density (Nv) of symmetrical synapses associated with flat vesicles (FS synapses) but not of asymmetrical synapses associated with round vesicles (RA synapses). Since many of the environment-sensitive properties of visual cortex neurons are GABA-dependent, it was suggested that the interindividual differences in FS synapses might be due to environmental factors. To verify this possibility we estimated the Nv of both types of synapses in two groups of six cats, paired by litter and by sex, and raised either in isolation or in a colony from the time of weaning to the age of 8 months. We also measured the Nv of neurons and the thickness of the cortex and made some gross anatomical measurements. The brains of animals raised in the enriched environment are 7% heavier, and their total body weight is 10% greater: The brain-to-body-weight ratio remains unchanged. The total length of the brain is not affected, but the length and width of the cerebral hemispheres are each 5% greater in the enriched cats. As in comparable rat studies, the thickness of the cortex is 4% greater, but in the present study this difference is not significant. The numerical density of neurons is diminished by 17% in enriched animals. This is probably due to a wider separation of neuronal cell bodies in a larger cortical volume, rather than to a loss of neurons. There are no significant changes in the numerical density of RA synapses between the two milieux, but there are nearly twice as many FS synapses per mm3 of tissue in the impoverished cortex. The coefficient of variation of FS synapses, which in the previous study was on the order of 30%, has been reduced to 10% and 7% in enriched and impoverished cats, respectively. We conclude that environmental conditions can lead to selective interindividual differences in the Nv of FS synapses, as seen in our previous study of animals whose rearing conditions were not controlled. The average diameter of RA synaptic profiles is not affected by the environment but FS synapses are 25% wider in the enriched animals. Because of the smaller neuronal Nv in enriched animals, there are, in fact, 18% more RA synapses and 34% fewer FS synapses per neuron in the enriched condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Immunohistochemical localization of the S-100 beta protein in postnatal cat visual cortex: spatial and temporal patterns of expression in cortical and subcortical glia.

The ontogenic expression of the glial-specific protein S100 beta was examined in postnatal cat visual cortex using immunocytochemical methods. Astrocytes in visual cortex and oligodendrocytes in the subcortical white matter exhibited distinct spatio-temporal gradients in their expression of the S100 beta protein. In the visual cortex, S100 beta-immunoreactivity was detected in astroglial cytoplasm, as well as in the extracellular interstitium, in a lamina-specific manner throughout postnatal development. Using double labeling procedures, the S100 beta protein was found to be strictly colocalized with GFAP-immunoreactive astrocytes when GFAP was present. The glial fibrillary acidic protein (GFAP), a marker of mature astrocytes, was not present at high levels until the 4th postnatal week. From the 2nd through 5th postnatal weeks, the expression of S100 beta was highest in the thalamocortical recipient, layer IV, of visual cortical areas 17 and 18. At ages beyond 6 postnatal weeks, S100 beta-immunoreactivity increased disproportionately in supra- and infragranular layers such that areas 17 and 18 were demarcated from adjacent cortices by lower levels in layer IV. The S100 beta protein was also highly expressed in oligodendroglial somata and processes in the subcortical white matter between the 2nd and 6th postnatal weeks. The levels of S100 beta in the subcortical white matter progressively diminished to adult levels, where it was localized only to a few remaining oligodendroglial somata. The differential laminar expression of the S100 beta protein in astrocytes during the period within which the visual cortex exhibits input- and experience-dependent synaptic modifications suggests that astrocytes, possibly via their release of S100 beta, may play a special role in mediating plasticity in visual cortical development. A consistent feature of the appearance of the S100 beta protein was its expression in immature astroglia and oligodendroglia, well before they are considered morphologically mature. This characteristic underscores the potential of S100 beta as a marker of distinct populations of glial cells and of their role in normal and abnormal development.

Animals

Transient co-localization of calretinin, parvalbumin, and calbindin-D28K in developing visual cortex of monkey.

This paper reports a double-labelling immunocytochemical study of the three calcium-binding proteins calretinin, parvalbumin, and calbindin-D28k in developing and adult Macaca primary visual cortex. In adult visual cortex, each protein marks a subset of GABAergic neurons with a characteristic laminar distribution and virtually no co-localization was found between these three proteins, suggesting that each calcium-binding protein may serve as a marker for one or more cortical subcircuits. The immature visual cortex, immunostained using identical techniques was then analysed to determine if each calcium-binding protein could serve as a developmental marker for these circuits. The Cajal-Retzius cells of layer 1 contained all three proteins during development. Calbindin-D28k and calretinin were co-localized starting at Fd (foetal day) 45 and after Fd125, parvalbumin also was present in the same Cajal-Retzius cells. All three proteins continued to be expressed until the Cajal-Retzius disappeared postnatally. In layers 2-6 calbindin-D28k and calretinin were never co-localized. In contrast, parvalbumin and calretinin were found in neurons of deep layer 3 from Fd 155 to postnatal (P6) weeks with a few persisting even later. Before birth almost all PV+ neurons in layers 4-6 were CaB+, but by P3 weeks only a few PV+/CaB+ neurons remained in layer 4C and these completely disappeared by P6 weeks. Co-localization in layer 4 neurons overlaps the period of ocular dominance segregation, suggesting that the onset of cortical maturity coincides with segregation of calcium-binding proteins within the GABA interneurons.

Animals

The in vitro slice preparation for combined morphological and electrophysiological studies of rat visual cortex.

The morphological condition of slices of rat visual cortex, maintained in vitro in an interface-type recording chamber, was assessed. In addition, neurones in these slices were impaled with glass micropipettes for intracellular recording and horseradish peroxidase (HRP) injection. After fixation and embedding, slices were examined by light and electron microscopy. Slices sectioned orthogonally to the original plane of cutting showed a vertical zonation of tissue preservation. The upper zone contained dense and flattened neuronal somata, although the neuropil appeared normal. The central zone was well preserved, with the appearance of most somata, dendrites, axons and synapses comparing favourably with perfusion-fixed material. The lower zone contained many abnormal, vacuolated somata. The morphology of HRP-injected neurones was assessed by light microscopy. Dendrites could be visualised in great detail and spines were clearly visible. Local axon arbors were well represented. There was good correlation between electrophysiological and morphological criteria for the assessment of the condition of the slice. We conclude that, provided the extent of degeneration within the slice is monitored and appreciated, slices of visual cortex can provide both electrophysiological and morphological data of high quality.

Animals

[Characteristics of the response of rabbit visual cortex neurons to intracortical electric stimulation].

Responses of visual cortex neurons to single and rhythmical intracortical electrical stimulation were investigated in rabbits. Stimulating and recording electrodes were separated by 0.7-1.2 mm. Thresholds of responses to single stimuli were in general about 150-180 microA, to serial stimuli -- 30-60 microA. Latency of the first spike was 5-15 ms, but probability of discharge was very low (3-6%). The length of the inhibitory phrase in the response increased in a half of the investigated neurons with the increase in the stimulus strength. Spontaneous activity after a series of stimuli increased during 4-6 s. Repeated single stimuli induced in about a half of the investigated neurons the same types of dynamic modifications in activity, as those produced by light stimulation. However, in response to electrical stimulation more neurons developed discharge sensitization and less habituation. It is supposed that intracortical stimulation induces in the visual cortex excitation of local hypercolumns and inhibition of the neighbouring ones.

Animals

Remote astrocytic response as demonstrated by glial fibrillary acidic protein immunohistochemistry in the visual cortex of dorsal lateral geniculate nucleus lesioned rats.

The reaction of astroglia was investigated after unilateral destruction of the dorsal lateral geniculate nucleus in the primary visual cortex of adult albino rats. The destruction of the dorsal lateral geniculate nucleus was performed by stereotaxic injections of ibotenic acid, and the location was verified in Nissl stained sections in each animal. Electron microscopic observations demonstrated the presence of degenerating axon terminals surrounded by hypertrophic astroglial processes mainly in layers III and IV of the ipsilateral primary visual cortex. The ipsilateral (impaired) and contralateral (control) sides of the primary visual cortex showed light microscopically a clearly differing appearance and distribution of glial fibrillary acidic protein (GFAP) immunoreactivity 7 to 11 days after the unilateral injection of ibotenic acid into the dorsal lateral geniculate nucleus. Whereas the control side of the primary visual cortex showed GFAP staining only in the subpial zone of layer I and close to the white matter, all layers of the impaired cortex showed an intense GFAP immunoreactivity. The increase in immunoreactivity was confined to the primary visual cortex. The extent of and increase in immunoreactivity was corroborated by image analysis. These findings were interpreted as a localized hypertrophy of astroglia caused by the anterograde degeneration of geniculocortical terminals. This hypertrophy is accompanied by an increase in GFAP, which may represent the stabilization of the cytoskeleton of newly formed glial processes involved in the rearrangement of the impaired neuropil.

Afferent Pathways

The development of MK-801, kainate, AMPA, and muscimol binding sites in cat visual cortex.

Previous work using homogenate binding has shown that the development of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10imin e maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the height of the plastic period, and decreases in adulthood. We have studied the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the development of other binding sites in the visual cortex. After confirming the original finding, we extended it by showing that the sensitivity of MK-801 binding sites to glutamate and glycine decreases when the cat becomes an adult. We then examined the regional specificity of MK-801 binding. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 days to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adulthood was less dramatic in the hippocampus than in the visual cortex and was statistically significant only when binding was measured per milligram protein. Saturation analyses also showed a difference in the two structures. Bmax in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these developmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and muscimol. Like MK-801, kainate binding increased from 7 days to 42 days and decreased from 42 days to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly from 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate binding suggests that their associated receptors may have a role in determining the plastic period of visual cortex.

Aging

Optimal spatial displacement for direction selectivity in cat visual cortex neurons.

Responses of single neurons in cat visual cortex were measured in response to sinewave grating stimuli. Firstly, a neuron's spatial frequency tuning was determined, and subsequent stimuli were set at the optimal spatial frequency for that neuron. Then a "jumping grating" stimulus was used: a sinewave grating subjected to a series of abrupt spatial displacements, while remaining stationary for a fixed exposure time between displacements. The amount of direction selectivity elicited by this stimulus was measured as a function of the amount of spatial displacement. Visual cortex neurons generally showed an optimal spatial displacement, corresponding to somewhat less than one quarter of a spatial period of the neuron's optimal spatial frequency (close to, but systematically less than, "quadrature phase"). In a majority of neurons tested, this optimal displacement was not affected by increasing the exposure time between displacements, indicating that the measurements were not a simple consequence of temporal frequency tuning. These results closely parallel recent human psychophysical data obtained from measurements of motion aftereffect or direction discrimination elicited by jumping grating stimuli.

Animals

Processes of visual recognition in monkeys and their neuronal correlates in the visual cortex: the influence of a blocker of M-cholinoreceptors.

The activity of individual neurons of the visual cortex was recorded simultaneously in behavioral experiments on monkeys before and after the systemic administration of a blocker of M-cholinoreceptors, amizil (0.8-1.0 mg/kg). The animals were trained to delayed visual differentiation of stimuli of various colors. After the administration of amizil, the characteristics of recognition deteriorated substantially: the duration of the storage of information in short-term memory sharply declined, while the time of the motoric reaction increased. The deterioration of these characteristics was accompanied by inhibition of the activity of the neurons of the visual cortex, inhibition which depended on the stage of recognition, and which intensified when there was an increase in the delay interval. The results obtained suggest that cholinergic mechanisms of the visual cortex are included in visual recognition, and apparently play various functional roles at various stages of behavior.

Animals

Squint affects synchronization of oscillatory responses in cat visual cortex.

As shown previously, neurons in various areas of the cat's visual cortex respond to appropriate visual stimuli with oscillatory activity in the frequency range of 30-70 Hz. It has been suggested that synchronization of such responses serves to define assemblies of coherently active cells which represent individual visual objects. In this study, we have investigated this putative binding mechanism in the visual cortex of strabismic cats. We used six adult cats in which divergent squint had been induced surgically at the age of 3 weeks. Multiunit activity was recorded from area 17 with arrays of four or five closely spaced microelectrodes. Subsequently, auto- and cross-correlation functions were computed for all spike trains. To quantify the oscillatory nature of the responses and the strength of synchronization between spatially remote sites, damped sine wave functions were fitted to the correlograms. Analysis of responses obtained from 202 recording sites showed that the vast majority of cells had become monocular. Auto-correlation analysis revealed that the proportion of oscillatory firing patterns was similar to that observed in normal cats. However, cross-correlation analysis of 153 response pairs demonstrated that synchronization was reduced significantly between cells dominated by different eyes while it was as frequent and strong as in normal cats between cells dominated by the same eye. These findings indicate that strabismus not only causes a reorganization of afferent inputs but also affects intracortical interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Endstopped neurons in the visual cortex as a substrate for calculating curvature.

Neurons in the visual cortex typically respond selectively to the orientation, and velocity and direction of movement, of moving-bar stimuli. These responses are generally thought to provide information about the orientation and position of lines and edges in the visual field. Some cells are also endstopped, that is selective for bars of specific lengths. Hubel and Wiesel first observed that endstopped hypercomplex cells could respond to curved stimuli and suggested they might be involved in detection of curvature, but the exact relationship between endstopping and curvature has never been determined. We present here a mathematical model relating endstopping to curvature in which the difference in response of two simple cells gives rise to endstopping and varies in proportion to curvature. We also provide physiological evidence that endstopped cells in area 17 of the cat visual cortex are selective for curvature, whereas non-endstopped cells are not, and that some are selective for the sign of curvature. The prevailing view of edge and curve determination is that orientations are selected locally by the class of simple cortical cells and then integrated to form global curves. We have developed a computational theory of orientation selection which shows that measurements of orientation obtained by simple cells are not sufficient because there will be strong, incorrect responses from cells whose receptive fields (RFs) span distinct curves (Fig. 1). If estimates of curvature are available, however, these inappropriate responses can be eliminated. Curvature provides the key to structuring the network that underlies our theory and distinguishes it from previous lateral inhibition schemes.

Animals

Functional organization of lateral geniculate cells following removal of visual cortex in the newborn kitten.

When the visual cortex of a newborn kitten is removed, most neurons in the dorsal lateral geniculate nucleus degenerate, but a small population of large cells is spared. Electrophysiological recording revealed that detailed visual topography in the nucleus is abnormal and that single cells have unusually large receptive fields. These results suggest that optic axons deprived of their normal synaptic targets rearrange their connections to converge on local surviving neurons.

Animals

Distribution and morphology of functionally identified neurons in the visual cortex of the rat.

The distribution and morphology of functionally identified neurons were examined in the visual cortex of Long Evans pigmented rats. The results, based on qualitative and quantitative analysis of single cell spike activity, have shown that neurons in the rat visual cortex have well-defined receptive field properties and are similar to those reported for animals with more highly developed visual systems. Unlike the cat and monkey, the distribution of receptive field types appeared even throughout the visual cortex. Exception was provided by layer IV which, similar to the more 'visual' animals, contained the largest percentage of simple cells. Horseradish peroxidase injected into single, physiologically identified neurons allowed for detailed morphological characterization of functional cell types. Of the cells successfully filled with horseradish peroxidase, complex cells were pyramidal in morphology and located in layers II through VI. Simple cells were both pyramidal and non-pyramidal in appearance and were located in layers II + III and IV. Finally, hypercomplex cells were pyramidal in appearance and their perikarya were situated in layers II + III and V.

Animals

Amphetamine-induced recovery of visual cliff performance after bilateral visual cortex ablation in cats: measurements of depth perception thresholds.

After bilateral visual cortex ablation, cats exhibit a loss of depth perception as measured on a visual cliff, which recovers following administration of d-amphetamine. In this Study, 3 amphetamine-treated cats with visual cortex ablations showed a rapid and enduring recovery, with 2 of these animals obtaining levels of performance seen only with binocular vision, suggesting a restoration of binocular depth perception. Cats with asymmetrical lesions showed only a transient improvement during amphetamine treatment, and some animals not displaying autonomic signs of amphetamine intoxication did not improve. Saline-treated cats showed no signs of improvement, and the effect of amphetamine was blocked by the catecholaminergic antagonist haloperidol. These results indicate that amphetamine can induce an enduring recovery from a behavioral deficit after brain injury, which if left untreated would not spontaneously recover.

Amphetamine

Differential effects of quinolinic acid lesions on muscarinic acetylcholine receptors in cat visual cortex during postnatal development.

Quinolinic acid (QA) lesions of neurons in cat visual cortex were combined with conventional in vitro autoradiographic methods in order to define the cellular locus of the muscarinic acetylcholine receptor (mAChR). Animals of various postnatal ages had QA unilaterally injected into the visual cortex. Four to fourteen days later they were sacrificed and processed for electron microscopy (EM) or in vitro autoradiography. QA lesions at the various postnatal ages were found to eliminate intrinsic cortical neurons and their processes while leaving intact glia, fibers of passage and axon terminals from outside the lesion zone. Autoradiograms of visual cortex labelled with [3H]QNB (which labels M1 and M2 subtypes) showed an age-dependent loss of binding sites, with the greatest decreases occurring after 65 days postnatal. Examined separately, only the M1 mAChRs labelled with [3H]pirenzepine exhibited these age-dependent alterations. The results indicate a differential distribution of the M1 mAChRs during postnatal development. The loss of receptors late in postnatal life following QA suggests a dominantly neuronal locus; the relatively small loss early in postnatal life suggests a locus on other cellular elements.

Aging

[Differences in the properties of 2 groups of orientation detectors of the visual cortex in the cat].

Functional properties of 149 neurons in field 17 of the visual cortex were studied in immobilized cats. They were divided into two groups. In 37% of neurons the initial and peak latencies of responses changed not more than by 10 ms in the orientation range. They were named "timer"-neurons. 63% of neurons were called "scanners". "Timers" reliably differed from "scanners" in shorter latencies, time of the discharge frequency increase, duration of the response and higher discharge frequency in all stimuli orientations. Scanners had a higher orientation selectivity, they considerably more often scanned the range of orientations in time. Neurons of the two groups had contraphase dynamics of the width of tuning orientation during response while distribution of their preferential orientations supplemented each other. In orientation columns of the visual cortex, both timers and scanners were most often found with a predominance of the latter. The columns consisting of only timers or only scanners were more seldom. The role of differences in properties of two neuronal groups in the cat visual cortex for orientation detection is discussed.

Animals

Muscarinic acetylcholine receptor subtypes in rat visual cortex--a comparative study using quantitative receptor autoradiography and in situ hybridization.

The laminar pattern of M1- and M2-muscarinic acetylcholine receptors (mAChR) in rat visual cortex has been compared with the distribution of the corresponding m1, m2, m3 and m4 receptor genes using both quantitative receptor autoradiography and in situ hybridization histochemistry. The laminar distribution of 3H-pirenzepine binding to M1-mAChRs in rat visual cortex shows a bimodal pattern with higher binding levels in upper layer III and deeper layer VI. In contrast, highest binding of 3H-AF-DX384 to M2-mAChRs was observed in upper layer IV (100%) and upper layer VI (about 80% of highest binding). The m1 receptor mRNA is almost homogeneously distributed throughout the visual cortex, whereas the m2mAChr mRNA predominates in layer IV with lower levels in layers I and V. The highest amounts of m3mAChR mRNA in rat visual cortex were observed in layer II, while the distribution of m4mAChR transcripts shows a bimodal pattern with peaks in layers III and upper layer VI. The distinct laminar pattern of mRNA muscarinic receptor subtypes in rat visual cortex suggest specific roles of the muscarinic receptor in visual function.

Animals

Evidence for a laminar organization of basal forebrain afferents to the visual cortex.

The present study shows that restriction of HRP injections to layer I within the visual cortex results in negligible retrograde labeling within the nuclei of the basal forebrain. In contrast, when the injections of either HRP or WGA-HRP are restricted to the granular and infragranular layers of visual cortex, extensive retrograde labeling occurs within the basal forebrain. Based upon these findings, we argue that the projection from the basal nucleus terminates preferentially within the deep layers of the visual cortex, and thus contributes minimally to the supragranular layers, including layer I.

Acetylcholinesterase