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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↗

Right and left visual cortex areas in healthy subjects with right- and left-eye dominance.

The aim of this work was to study the differences between the right- and left-visual cortices in relation to eyedness in healthy subjects. Ocular dominance was determined by means of the near-far alignment test. To assess visual cortical areas, the right and left sagittal scenograms of cranium by magnetic resonance imaging were used. To calculate the visual cortex areas by using scenograms, Cavalieri's method was used. In the subjects with right-eye dominance, the right visual cortex was larger than the left visual cortex, and vice versa in the subjects with left-eye dominance. The right and left cuneal areas were found to be larger in males than in females. In light of these results, it was concluded that the human eyes are predominantly controlled by the ipsilateral visual cortex.

Adolescent↗

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↗

Ischemia increases prostaglandin H synthase-2 levels in retina and visual cortex in piglets.

BACKGROUND: Ischemia increases levels of prostaglandin H synthase-2 (PGHS-2) in neonatal brain and cerebral vasculature, but effects on the developing visual system are unknown. We examined the effects of ischemia on PGHS-2 mRNA and protein levels in the retina and visual cortex in anesthetized piglets. METHODS: Ten minutes of complete retinal and brain ischemia was induced by increasing intracranial pressure. After 2-12 h of reperfusion, samples of retina and visual cortex were collected for determinations of levels of PGHS-2 mRNA (RNase protection assay) or protein (immunohistochemistry and western blotting). Tissues also were obtained from control animals. RESULTS: Levels of PGHS-2 mRNA were undetectable in control animals but showed a dramatic increase at 2-4 h in the cortex and retina in animals exposed to ischemia. Detectable but limited PGHS-2 immunoreactivity (IR) was present in the retina and visual cortex from control animals. In piglets not subjected to ischemia, PGHS-2 IR was localized mainly to the outer limiting membrane and to the Muller cells. Ischemia induced a marked increase in PGHS-2 IR in the neural retina, with the greatest increase in the photoreceptor layer. PGHS-2 levels in whole retina also increased at 8 h after ischemia. In the intact visual cortex PGHS-2 IR was evident in layers II and V. Ischemia increased the intensity of IR in layers II/III as well as layer V. CONCLUSIONS: Detectable amounts of PGHS-2 protein are present in the piglet retina and visual cortex under normal conditions, but levels are markedly increased 8-12 h after ischemic stress. Enhanced PGHS-2 levels after ischemic stress may contribute to delayed pathological changes of the visual system in the neonate.

Animals↗

Is there a BOLD response of the visual cortex on stimulation of the vision-related acupoint GB 37?

PURPOSE: To determine whether or not acupuncture of guangming (GB 37) produces a significant response of the visual cortex detectable by means of functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: This study investigates the activation of the visual cortex elicited by a soft and an intensified stimulation of GB 37, an acupoint documented to influence vision-related disorders. Three different paradigms were carried out to detect any possible modulation of the Blood Oxygenation Level Dependent (BOLD)-response in the visual cortex to visual stimulation through acupuncture. RESULTS: The percentage signal changes in the visual stimulation cycles did not significantly differ before vs. during acupuncture. CONCLUSION: Whereas no BOLD-response correlating with acupuncture was detected in the visual cortex, BOLD-signal-changes in response to needle twisting were detected in different cortical areas. Further studies are necessary to clarify whether these clusters correlate to inevitable somatosensory stimulation accompanying acupuncture or represent an acupuncture-specific response.

Acupuncture Points↗

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↗

Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex.

The NMDA receptor (NMDAR) is a heteromer comprised of NR1 and NR2 subunits. Mice that overexpress the NR2B subunit exhibit enhanced hippocampal LTP, prolonged NMDAR currents, and improved memory ( Tang et al., 1999). In the current study, we explored visual cortex plasticity and NMDAR function in NR2B overexpressing transgenic mice. Unlike the hippocampus, in vitro synaptic plasticity of the visual cortex was unaltered by NR2B overexpression. Consistent with the plasticity findings, NMDAR excitatory postsynaptic current (EPSC) durations from layer 2/3 pyramidal cells were similar in wild-type (wt) and transgenic (tg) mice. Furthermore, temporal summation of NMDAR EPSCs to 10, 20, and 40 Hz stimulation did not differ between cells from wt and tg mice. Finally, although in situ studies clearly demonstrate overexpression of NR2B mRNA in visual cortex, we failed to observe a significant elevation in the synaptic expression of NR2B protein. We conclude that the synaptic ratio of NR2B over NR2A in the NMDA receptor complex in the visual cortex is not significantly influenced by the transgene overexpression. These data suggest that mRNA availability is not a limiting factor for the synthesis of NR2B protein in the visual cortex, and support the hypothesis that levels of NR2A, rather than NR2B, normally determine the subunit composition of NMDARs in visual cortex.

Animals↗

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↗

Sex and electroencephalographic synchronization after photic stimulation predict signal changes in the visual cortex on functional MR images.

PURPOSE: We evaluated factors that influence MR signal changes during photic stimulation of the visual cortex. We also tested the hypothesis that functional MR imaging response corresponds to electroencephalographic (EEG) synchronization after photic stimulation. METHODS: Thirty-eight healthy subjects, 20 men and 18 women, underwent photic stimulation of the visual cortex. They were studied with a 1.5-T MR unit, and photic stimulation was induced via 8-Hz LED goggles. Seven subjects with and seven without detectable functional MR imaging response to photic stimulation underwent further studies with 16-channel EEG after 2- to 30-Hz stroboscopic stimulation. RESULTS: Thirteen men and 18 women had a significant increase in MR signal in the visual cortex; seven men showed no visual cortex activation during more than two repeated studies. Six of seven volunteers with increased functional MR imaging signal after photic stimulation also showed signs of EEG synchronization when an 8-Hz stroboscopic flash was used; six of seven subjects with no functional MR imaging lacked EEG synchronization at 8-Hz stimulation. CONCLUSIONS: Men were more likely than women to have undetectable MR signal changes after photic stimulation. This finding should be considered when interpreting results of functional MR imaging studies. EEG with stroboscopic examination is a good predictor of functional MR imaging sensitivity to changes in regional cerebral blood flow induced by sensory stimulation.

Adult↗

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↗

Roles of protein kinase A and protein kinase G in synaptic plasticity in the visual cortex.

Monocular deprivation leads to clear physiological and anatomical changes in the visual cortex known as ocular dominance plasticity. Protein kinase A (PKA) is necessary for ocular dominance plasticity, while protein kinase G (PKG) is not. We have now tested the role of PKA and PKG in long-term potentiation (LTP) and long-term depression (LTD). We have shown that PKA inhibitors have a major effect on both LTP and LTD in the visual cortical slices, whereas a PKG inhibitor affects LTP but not LTD. The PKA activator, 8-chloroadenosine-3',5'-monophosphorothioate, Sp-isomer (Sp-8-Cl-cAMPS), by itself induces a slowly rising form of LTP, which is occluded by theta-burst stimulation (TBS)-induced LTP. These results support the point that the PKA signaling pathway is crucial for neuronal plasticity in visual cortex, and the dissociation of the role of PKA and PKG in long-term synaptic plasticity in the visual cortex suggests that LTP alone is not sufficient to support ocular dominance plasticity, or LTD plays a more fundamental role than LTP in ocular dominance plasticity.

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↗