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PubMed2004

Time-dependent changes in the expression of the MEF2 transcription factor family during topographic map reorganization in mammalian visual cortex.

Removal of retinal input from a restricted region of adult mammalian visual cortex leads to a substantial reorganization of the retinotopy within the lesion projection zone (LPZ) of primary visual cortex (area 17). Little is known about the molecular mechanisms underlying such cortical plasticity. We investigated whether small but homonymous central retinal lesions induced differences in gene expression patterns between central area 17, the LPZ, vs. peripheral area 17 of the adult cat. Systematic differential mRNA display screening revealed higher levels for the mRNA encoding the transcription factor MEF2A in the LPZ. Semi-quantitative PCR confirmed this dependency of mef2A mRNA expression on visual eccentricity in area 17 of animals with retinal lesions in contrast to normal animals. Western blotting experiments extended these data to the protein level and to two other members of the MEF2 transcription factor family, i.e. MEF2C and MEF2D. Quantitative analysis of the Western blotting experiments further revealed a post-lesion survival time-dependent change in expression for all three MEF2 family members. The lesion effect was maximal at 3 days and 1 month post-lesion, but only minor at 2 weeks post-lesion. Interestingly, complete removal of retinal input from area 17 by surgery did not significantly alter the expression of the MEF2 transcription factors, excluding a definite correlation between neuronal activity and MEF2A expression levels. MEF2A immunocytochemistry confirmed both qualitatively and quantitatively the Western blotting observations in all animal models. Together, our findings identified a brain plasticity-related expression pattern for the MEF2 transcription factor family in adult mammalian neocortex.

Animals↗
PubMed1995

Monocular deprivation decreases the expression of messenger RNA for brain-derived neurotrophic factor in the rat visual cortex.

We found that deprivation of pattern vision in one eye, that leaves luminance detection performance unaffected, is sufficient to reduce brain-derived neurotrophic factor (but not trkB) messenger RNA in the visual cortex of young and adult rats. Monocular deprivation by means of eyelids' suture was performed during or after the critical period and the cortical amount of brain-derived neurotrophic factor messenger RNA was analysed by in situ hybridization and RNAase protection after 15-30 days of deprivation. A reduction of brain-derived neurotrophic factor messenger RNA was observed in the visual cortex contralateral to the deprived eye in rats monocularly deprived during the critical period. The same reduction was also found in rats monocularly deprived after the end of the critical period, when anatomical or physiological signs of monocular deprivation are absent. The pharmacological blockade of retinal activity equally affected the expression of brain-derived neurotrophic factor messenger RNA in young and adults. Quantitative RNAase protection assays revealed that the cortical level of brain-derived neurotrophic factor messenger RNA was reduced to the same extent when intraocular injections of tetrodotoxin were performed within or after the critical period. A developmental study of brain-derived neurotrophic factor messenger RNA expression in rat visual cortex showed a marked increase around the time of natural eye-opening followed by a plateau from postnatal day 20 until adult age. Messenger RNA for the kinasic domain of brain-derived neurotrophic factor receptor (trkB) was found in the dorsal lateral geniculate nucleus and the visual cortex during development and in adults. Our results suggest that the reduction of brain-derived neurotrophic factor messenger RNA induced by monocular deprivation is related to the absence of pattern vision rather than to the competitive interactions that underlie the effects of monocular deprivation during the critical period.

Age Factors↗
PubMed1999

Asymmetric suppression outside the classical receptive field of the visual cortex.

Areas beyond the classical receptive field (CRF) can modulate responses of the majority of cells in the primary visual cortex of the cat (). Although general characteristics of this phenomenon have been reported previously, little is known about the detailed spatial organization of the surrounds. Previous work suggests that the surrounds may be uniform regions that encircle the CRF or may be limited to the "ends" of the CRF. We have examined the spatial organization of surrounds of single-cell receptive fields in the primary visual cortex of anesthetized, paralyzed cats. The CRF was stimulated with an optimal drifting grating, whereas the surround was probed with a second small grating patch placed at discrete locations around the CRF. For most cells that exhibit suppression, the surrounds are spatially asymmetric, such that the suppression originates from a localized region. We find a variety of suppressive zone locations, but there is a slight bias for suppression to occur at the end zones of the CRF. The spatial pattern of suppression is independent of the parameters of the suppressive stimulus used, although the effect is clearest with iso-oriented surround stimuli. A subset of cells exhibit axially symmetric or uniform surround fields. These results demonstrate that the surrounds are more specific than previously realized, and this specialization has implications for the processing of visual information in the primary visual cortex. One possibility is that these localized surrounds may provide a substrate for figure-ground segmentation of visual scenes.

Animals↗
PubMed1995

Motion-from-hue activates area V5 of human visual cortex.

We designed experiments to ascertain whether area V5 of human visual cortex is activated by a motion stimulus in which luminance is made irrelevant, and motion is generated from hue differences alone. The stimuli consisted of moving green squares or bars against a red background, masked with luminance noise. Changes in regional cerebral blood flow (rCBF) were determined by the technique of positron emission tomography and the brain images thus derived were co-registered with magnetic resonance images of the same brain to identify the anatomical locations of the blood flow changes. The results showed that when subjects perceived motion, a change in rCBF occurs in areas V5, V1/2, V3 and the parieto-occipital sulcus but not V4, even though the moving stimulus was defined by hue. We conclude that the motion-specialized areas of the visual cortex can use information derived from any source to undertake their function.

Brain Mapping↗
PubMed1994

Temporal covariance of pre- and postsynaptic activity regulates functional connectivity in the visual cortex.

1. It has been suggested from mathematical models and in vivo experiments in the visual cortex that periods of temporal covariance of pre- and postsynaptic activity can lead to a potentiation or depression of synaptic efficacy. We directly tested this hypothesis in vitro in the guinea pig and cat visual cortex. 2. Intracellular recordings were made in brain slices from 63 neurons in layers 2-4 in bicuculline-free artificial cerebrospinal fluid. Twenty-nine cells (n = 25 from pigmented guinea pigs and 4 from cats) were taken through a complete series of control and test protocols to evaluate the covariance hypothesis. Some (n = 7) cells that were taken through the complete experimental protocols were also filled intracellularly with biocytin. Compound postsynaptic potentials (PSPs) were evoked by low-frequency (0.2-1.0 Hz), weak (20% of threshold intensity) stimulation of the cortical white matter and/or intracortical sites in layers 2-3. 3. In one series of experiments we paired PSPs with imposed coincident depolarizing (S+) or hyperpolarizing (S-) pulses (mean +/- 2.8 nA for 50-80 ms) of the postsynaptic neuron (n = 54 PSPs; > 1 pairing protocol was often run on an individual cell). Controls consisted of analyzing the same number of S+ or S- pairings but with long temporal delays [called fixed delay pairings (FDPs)] between the test pathway stimulation and the onset of the intracellular current pulse (120 ms) and pseudopairings (PP) consisting of evoked PSPs and delivery of intracellular current injection pulses in a phase-independent manner. Twenty-one of 54 PSPs subjected to pairing were significantly modified by the protocol. The S+ protocol significantly (P < 0.05, Kolmogorov-Smirnov test) increased the peak amplitudes of 8 of 22 PSPs (+20 to +55%); the S- protocol significantly decreased the peak amplitudes of 13 of 32 PSPs (-15 to -88%), whereas the FDP and PP protocols generally did not cause significant changes in the PSPs (0% and 4%, respectively). Significant changes in PSPs persisted in most cases for 10-20 min. 4. Another series of experiments consisted of evaluating for the same cell the effects of evoking a PSP from one stimulation site without concomitant postsynaptic activation and alternately evoking a PSP from the other stimulation site with S+ or S- pairing (n = 25 PSPs). Only the paired pathway showed the predicted effects on the PSP (S+ pairing causing an increase in peak PSP amplitude and S- pairing causing a decrease in peak PSP amplitude).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Development of local circuits in human visual cortex.

How we see the world largely depends on the organization of neuronal circuits in visual cortex. Physiological recordings in mammals indicate that circuits develop over a period that extends well into early postnatal ages (LeVay et al., 1980; Albus and Wolf, 1984). Our understanding of how these circuits are assembled during development is still fragmentary (Katz and Callaway, 1992). Here we describe the development of local connections within visual cortex, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to trace axonal projections in post-mortem human brains. Vertical (intracolumnar) connections between layers 2/3 and 5, which link neurons representing the same point in the visual field, develop prenatally at 26-29 weeks gestation. In contrast, horizontal (intercolumnar) connections between different points in the visual field develop later. They first emerge prenatally at approximately 37 weeks gestation within layers 4B and 5. After birth (> 40 weeks gestation) the fiber density increases rapidly, showing a uniform plexus of connections at 7 weeks postnatal. The more adult-like patchiness of the projection, however, emerges after 8 weeks postnatal. Long-range horizontal connections within layer 2/3 develop after the connections within layers 4B, 5, and 6. These connections emerge after 16 weeks postnatal, long after cytochrome oxidase blobs have developed, and reach mature from sometime before 15 months of age. Unlike the patchy horizontal projections within layers 4B and 5, which seem to develop through a process of collateral elimination, long-range projections within layer 2/3 are patchy from the outset and seem to develop with greater topographical precision. The finding that intracolumnar connections develop before intercolumnar projections suggests that circuits that process local features of a visual scene develop before circuits necessary to integrate these features into a continuous and coherent neural representation of an image. In addition, the sequential development of horizontal connections within layer 4B before those within layer 2/3 suggests that circuits that may be related to the processing channel for visual motion develop in advance of those that may be more intimately related to the processing of form, color, and precise stereoscopic depth.

Aging↗
PubMed1993

High frequency (60-90 Hz) oscillations in primary visual cortex of awake monkey.

It has been proposed that synchronized oscillations play a key role in perceptual feature linking and sensory integration. This idea was supported by the discovery of strongly synchronized stimulus-specific oscillations in the visual cortex of anaesthetized cats. The 'synchronization hypothesis' was controversial because in the visual cortex of awake monkeys either only weak or no oscillations were found. We have now recorded high amplitude synchronized oscillation at the level of spike activity and local field potential from the primary visual cortex of an awake monkey. The dominant frequencies (70-80 Hz) were considerably higher than those observed previously in cats and monkeys (30-50 Hz). However, stimulus specificities of the oscillations were comparable to and amplitudes even higher than those in cats.

Animals↗
PubMed1987

Distribution of neurons and glia in the visual cortex (area 17) of the adult albino rat: a quantitative description.

The neuronal and glial cell composition of the rat visual cortex (area 17) has been determined quantitatively using stereological techniques. The volume numerical densities (number of cells per mm3 of cortex) of neurons and of the principal glial cell types (astroglia, oligodendroglia, and microglia) were calculated from tangential semithin resin sections spaced at regular intervals 50 micron apart throughout the entire depth of the visual cortex. From measurements of cortical and laminar thickness the separate volume numerical densities of neurons and glial cells were derived for each lamina in the cortex. In addition, the absolute numbers of cells in each lamina under 1 mm2 of cortical surface were calculated. The mean cortical volume numerical density of neurons was 60,020 +/- 3840/mm3 (mean +/- SEM; n = 8), and 49,040 +/- 2610/mm3 for the combined glial cell types. Astroglia, oligodendroglia, and microglia were present in a ratio of 6:3:1 respectively. It was determined from neuronal and glial somatic volume estimates that the somata of these cells occupied approximately 13.5% of unit cortical volume, with 81.3% of the unit volume being occupied by cortical neuropil. Using previously published reports that described the laminar composition of neurons in terms of the relative proportions of pyramidal and non-pyramidal cells, the laminar volume numerical densities for these neuronal categories have been derived. In addition, it has been estimated that under 1 mm2 of cortical surface there are 79,500 pyramidal and 7790 non-pyramidal neurons distributed throughout layers 1-6 of the rat visual cortex.

Animals↗
PubMed2004

The organization of orientation and spatial frequency in primary visual cortex.

Many studies have demonstrated that the primary visual cortex contains multiple functional maps of visual properties (e.g., ocular dominance, orientation preference, and spatial-frequency preference), but as yet no consistent picture has emerged as to how these maps are related to one another. Three divergent, prior optical-imaging studies of spatial frequency are reanalyzed and critiqued in this article. Evidence is presented that a nonstimulus-specific response biased the interpretation of results in previous studies. In addition to reexamining four prior cat experiments, we carried out one new experiment. Through the use of different methods and a careful removal of the nonspecific response, we are led in all instances to a unique view of cortical organization for spatial-frequency preference. In particular, we find little apparent evidence for a columnar organization for spatial frequency. The response recorded by each image pixel may be viewed as arising from an admixture of low- and high-spatial-frequency populations. For most pixels, the ratio of these populations is 1:1.

Animals↗
PubMed1979

Projections to the visual cortex in the golden hamster.

Retrograde transport of horseradish peroxidase (HRP) was used to determine the origins of afferent connexions to the visual cortex (areas 17, 18a and 18b) in the hamster. The distribution of neurons projecting to the visual cortex from other cortical areas, from the thalamus and from the brainstem was studied using a computer technique for three-dimensional reconstruction. There is a topographically organized projection from the dorsal lateral geniculate nucleus to area 17, but probably to no other of the areas studied. The lateral posterior nucleus of the thalamus (LP) projects to area 18a and weakly to area 17. The lateral nucleus (L) projects to area 18b and also, probably, weakly to area 17. The cortical projections from LP and L are also organized topographically but relatively grossly compared with the geniculo-cortical pathway. There are reciprocal association projections between area 17 and areas 18a and 18b. Areas 18a projects weakly to 18b. The main commissural connexions of the posterior neocortex are between the area 17/18a boundary zones in the two hemispheres, with little between the bodies of area 17. Labelled neurons were found bilaterally in the locus coeruleus, more ipsilaterally than contralaterally, after multiple injections into the visual cortex: single, small injections sometimes resulted in the labelling of a single cell body in the locus coeruleus.

Animals↗
PubMed2006

Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study).

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion-sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction-dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compared with the control condition (stationary target) and with each other. Direction-dependent differences were not found in the cortical eye fields, but an asymmetry of activation occurred in paramedian visual cortex areas, and there were stronger activations in the hemisphere contralateral to the slow OKN phase (pursuit). This can be explained by a shift of the mean eye position of gaze (beating field) in the direction of the fast nystagmus phases of approximately 2.6 degrees, causing asymmetrical visual cortex stimulation. The absence of a significant difference in the activation pattern of the cortical eye fields supports the view that the processing of eye movements in both horizontal directions is mediated in the same cortical ocular motor areas. Furthermore, no hemispheric dominance for OKN processing was found in right-handed volunteers.

Adult↗
PubMed1997

Parallel processing streams in human visual cortex.

This study shows the existence in humans of independent neural processing streams in early visual cortex, which had previously been demonstrated in macaque monkeys. This evidence was obtained by controlled fixation testing of a subject who had suffered a small stroke in the right fusiform gyrus. The patient showed a severe disruption of color perception, shape discrimination and contrast sensitivity for stationary gratings in the upper left quadrant of his visual field. However, motion perception and contrast sensitivity for drifting gratings were relatively preserved. These results support the view that there are independent visual processing streams early in human visual cortex, and that these streams may subserve such functions as motion and color/form perception.

Cerebral Infarction↗
PubMed1994

The correlation between cortical neuron maturation and neurofilament phosphorylation: a developmental study of phosphorylated 200 kDa neurofilament protein in cat visual cortex.

Neurofilament proteins are major constituents of the neuronal cytoskeleton. When phosphorylated, neurofilament proteins are thought to be involved in slowing down the slower component of axonal transport, thereby increasing neurofilament stability and conferring resistance to proteolysis. In order to investigate the correlation between phosphorylated neurofilament and plasticity of the cat visual cortex, we applied a monoclonal antibody, which recognizes only the phosphorylated form of neurofilament protein, to kitten visual cortex. This antibody appeared to recognize only axons. There was a progressive increase of phosphorylated neurofilament-immunoreactive axons in the cortical layers and white matter during development. In the visual cortex of young kittens, phosphorylated neurofilament immunoreactive processes were mostly long, fine, and continuous axons. However, in kittens older than 2 months of age, phosphorylated neurofilament immunoreactivity was characterized by short, punctae-like staining. The immunoreactive axons were most dense in deep cortical layers V and VI initially, followed at later ages by layers IVa and IVb, and finally in layer IVc and in the superficial cortical layers of adult animals. This developmental laminar pattern of distribution was not affected by early input restriction and coincides with electrophysiological evidence of early neuronal maturation. In addition, the phosphorylated neurofilament immunoreactivity can also be found in the dendrites and perikaya of degenerating neurons. These results suggest that phosphorylated neurofilament can be used as an index of functional maturity in the kitten visual cortex and also as a marker for neurodegeneration.

Animals↗
PubMed1978

[Comparison of evoked potential changes from lateral geniculate body and visual cortex by stimulation of the medial septal nucleus and mesencephalic reticular formation in rabbits].

Evoked potentials to flash from visual cortex (VC) and corpus geniculatum laterale (Cgl) were observed in alert resting rabbits. The direction and volume of changes in the late negative complex (sn-) of the EP were investigated during repetition of light flashes only (habituation), during stimulation of septum and reticular stimulation (RFmes). Habituation showed an increase of amplitudes during the sn-complex, which was started first in Cgl, had its maximum earlier and lasted longer in the Cgl than in the visual cortex. Septal stimulation in the majority of experiments caused diminution of these EP-components almost synchronously in the VC and Cgl. Reticular stimulation gave rise to diminution of amplitudes during the sn-complex, which started first in the VC, where it had its maximum earlier and lasted longer than in the Cgl too. Our results show that all three influences under investigation caused typical but different changes of processes underlying EP of the visual cortex and lateral geniculate body.

Animals↗
PubMed2005

Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats.

The critical period for observing a developmentally regulated form of synaptic plasticity in the visual cortex of young rats normally ends at about postnatal day 30. This developmentally regulated form of in vitro long-term potentiation (LTP) can be reliably induced in layers II-III by aiming high frequency, theta burst stimulation (TBS) at the white matter situated directly below visual cortex (LTPWM-III). Previous work has demonstrated that suppression of sensory activation of visual cortex, achieved by rearing young rats in total darkness from birth, delays termination of the critical period for inducing LTPWM-III. Subsequent data also demonstrated that when rapid eye movement sleep (REMS) is suppressed, thereby reducing REMS cortical activation, just prior to the end of the critical period, termination of this developmental phase is delayed, and LTPWM-III can still be reliably produced in the usual post-critical period. Here, we report that for approximately 3 weeks immediately following the usual end of the critical period, suppression of REMS disrupts the maturational processes that close the critical period, and LTPWM-III is readily induced in brain slices taken from these somewhat older animals. Insofar as in vitro LTP is a model for the cellular and molecular changes that underlie developmental synaptic plasticity, these results suggest that mechanisms of synaptic plasticity, which participate in brain development and perhaps also in learning and memory processes, remain susceptible to the effects of REMS deprivation during the general period of adolescence in the rat.

Animals↗
PubMed2005

Differences between cation-chloride co-transporter functions in the visual cortex of pigmented and albino rats.

Albinism in mammals is accompanied by specific morphological and functional alterations of the visual system. To understand their cellular basis we studied the physiological characteristics and transmembrane currents of pyramidal neurons in 350-microm-thick slices of visual cortex from pigmented and albino rats using whole-cell and gramicidin perforated patch-clamp recordings. The resting membrane potential was significantly more positive and the rheobase was significantly lower in neurons of layers II/III and V in albinos as compared with pigmented rats. No significant differences were found in the input resistance, time constant and chronaxy. Whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated currents were not significantly different, the maximum gamma-aminobutyric acid (GABA)(A) receptor (GABA(A)R)-mediated currents and miniature inhibitory postsynaptic currents showed significantly lower amplitudes in neurons of layer V in visual cortex of albinos as compared with pigmented rats. The reversal potential of the GABA(A)R-mediated currents (E(GABA)) was significantly shifted to more positive values in albinos. Pharmacological experiments showed that this shift could be caused by an increased action of the inward chloride co-transporter NKCC1 and reduced action of the outward chloride co-transporter KCC2 in albino rats. This difference seems to be restricted to the visual cortex because in pyramidal neurons from frontal cortex E(GABA) was not significantly different in albinos as compared with pigmented rats. These results are discussed in relation to functional alterations in the albino visual system.

Animals↗
PubMed2003

Independence of visuotopic representation and orientation map in the visual cortex of the cat.

The representations of visual space and stimulus orientation were mapped in the cat primary visual cortex using electrophysiological recordings supplemented with intrinsic signal optical imaging. The majority of units displaced up to 600 micro m laterally had overlapping RFs both in orientation domains and around singularities of the orientation map. Quantitative comparison of these units revealed only a weak, positive correlation between the difference in their preferred orientations and RF separations (area 17: r = 0.09; area 18: r = 0.15). The occurrence of nonoverlapping RFs could be accounted for by random RF position scatter rather than by orientation difference between the units. Monte Carlo analysis showed that our findings are compatible with a locally smooth and linear representation of visual space that is not coupled to the representation of stimulus orientation. An important functional implication of the above map relationships is that positional information captured by the retina is faithfully transmitted into the cortex.

Animals↗
PubMed1991

Developmental changes of calcium currents in the visual cortex of the cat.

During a critical period of postnatal development the visual cortex of kittens is susceptible to experience-dependent modifications of neuronal response properties. Evidence is accumulating that these modifications are triggered by a transient neuronal calcium (Ca) influx. To further investigate this issue we measured extracellular Ca concentrations with ion-sensitive microelectrodes and compared the magnitude and the distribution of stimulus-evoked Ca fluxes in slices of the visual cortex of 4- to 5-week-old kittens and of 6-month-old adult cats. Stimulation of the white matter at 15 Hz for 8 s caused transient decreases of the extracellular Ca concentration (delta Cao) in slices of both age groups and in all cortical layers. However, there were developmental changes in the laminar distribution of the delta Cao: in kittens, they were maximal in layer IV whereas in adult cats they were most pronounced in the supragranular layers. The ratios between the amplitudes of delta Cao in layer IV and the supragranular layers were 1.65 +/- 0.26 in kittens and 0.43 +/- 0.2 in adult cats. These changes in laminar distribution resemble the laminar specific decay of neuronal malleability and parallel the developmental redistribution of 1,4-Dihydropyridine-sensitive Ca channels. Because of these correlations we interpret our findings as support for the hypothesis that experience-dependent modifications are triggered by Ca influx.

Aging↗