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[The rat visual cortex. Cytoarchitecture and stereotactic parameters].

In the present investigation the visual cortex of the albino rat was analyzed. On the basis of cytoarchitectonic criterions we can demarced the area striata (field 17) from a medial (field 18) and lateral (field 18a) lying peristriatic area. There are differences in the cortical structure not only between the striate and peristriate areae but also between field 18 and field 18a. In this publication we also present the visual cortex in stereotaxic coordinates on the basis of the stereotaxic atlas of FIFKOVA and MARSALA. Stereotaxic informations belonging the different fields of the visual cortex of the rat are not yet known, but they are very helpful for experimental investigations in this region of the brain.

Animals

Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex.

Alzheimer's disease (AD) visual cortex (area 17) was investigated using stains for plaques and tangles (Bielschowsky, thioflavine S) and gliosis (GFAP immunoperoxidase). Pathology was heaviest in layers II, III, IVa and IVc. Of especial interest was a thin line of plaques and astrocytic gliosis at the lower margin of layer IVc. These results could provide an insight into the pathogenesis of AD, and suggest that patients with AD may have specific visual deficits.

Aged

Dopaminergic innervation of the primary visual cortex in the rat, and some correlations with human cortex.

Dopaminergic terminals have been identified in the primary visual cortex with three techniques; immunocytochemistry with an anti-dopamine antiserum, retrograde axonal transport techniques using unconjugated wheat germ agglutinin and HPLC determination of catecholamines and metabolites in microdissected sub-regions of occipital cortex in the rat. The results demonstrate a specific dopaminergic innervation, arising from the ventral tegmental area, which is found mainly in laminae VI and V, but with minor innervation also in lamina I. Dopaminergic innervation to adjacent cortical regions is also described. Neurochemical data from post-mortem human material suggests that a similar innervation exists in man. An analysis of the distribution of dopaminergic fibres in relation to the known connections and possible functions of the deep laminae of visual cortex suggests that dopaminergic axons may participate in the corticofugal control of visual afferent pathways.

Aged

Dark-reared kittens: GABA sensitivity of cells in the visual cortex.

Most cells in the visual cortex of dark-reared kittens are unselective for stimulus orientation and we examined the notion that this might be due to insufficiently developed gamma-aminobutyric acid (GABA) receptors. We recorded from cortical neurons and examined their sensitivity to iontophoretically applied GABA. As expected, most units were non-selective for orientation, but application of GABA suppressed impulse activity of these cells just as for orientation selective neurons. This result suggests that the development or maintenance of GABA receptors is not critically dependent on visual experience.

Animals

Cellular organization and development of slice cultures from rat visual cortex.

Slice cultures from the visual cortex of young rats were prepared using the roller culture technique (Gähwiler 1984). After 10 days in vitro the cortical cultures flattened to 1-3 cell layers, surviving for up to 12 weeks. The cultures were organotypically organized, the typical layered structure of the cortex was preserved. The neuronal composition of slice cultures was studied using intracellular staining, Golgi impregnation and GABA immunohistochemistry. Both pyramidal cells and several types of nonpyramidal cells were identified in the slice cultures. Electrophysiological recordings showed that the electrical properties of cells in culture were similar to those measured in acute slice preparations; for some cells, however, the spontaneous activity was higher. The maintained activity was strongly increased by application of the GABA antagonist bicuculline and decreased by GABA, suggesting that GABAergic inhibition is present in these preparations. We could observe the postnatal maturation of some characteristic morphological features in culture. For example, pyramidal cells in 6 day-old rats in situ have very short basal dendrites with growth-cones, and the dendrites are free of spines. After 2-3 weeks in culture growth-cones were no longer observed. Instead, the cells had developed a large basal dendritic field and the dendrites were covered with spines. Slice cultures therefore may provide a useful tool for physiological, anatomical, pharmacological and developmental studies of cortical neurons in an organotypical environment.

Action Potentials

The effects of unilateral neonatal removal of visual cortex on transmitter parameters in the adult superior colliculus and lateral geniculate body.

High affinity glutamate uptake was reduced in the ipsilateral lateral geniculate body by 75% and in the ipsilateral superior colliculus by 50% one week after ablation of the visual cortex in the adult rat. Six days after neonatal removal of visual cortex, there were no effects on the high affinity glutamate uptake in these regions indicating that there were few functionally corticofugal fibres established at birth. Seventy-five days after unilateral neonatal ablation of visual cortex, the glutamate uptake in both ipsi- and contralateral superior colliculus was reduced 50% compared to unoperated controls. The glutamate uptake in the lateral geniculate body was reduced 55% ipsilateral to and 38% contralateral to the lesion. The neonatal lesion had therefore affected the development of glutamate nerve terminals bilaterally in these target regions. Destruction of the visual cortex on the unoperated side caused in these adults an additional bilateral decrease of the glutamate uptake in the superior colliculus, showing the presence of aberrant glutamatergic fibres crossing from the unoperated visual cortex. In the lateral geniculate body, a similar lesion was accompanied only by a reduction in glutamate uptake on the ipsilateral side. The neonatal ablation of visual cortex also induced small changes in glutamate decarboxylase and GABA uptake in superior colliculus 75 days after the operation.

Animals

[Characteristics of the stability of functional interhemispheric asymmetry in the cat visual cortex].

A study of EP topography in the cat visual cortex has shown that initial functional interhemispheric asymmetry may be reduced and replaced by symmetry through long and frequent binocular stimulation. Section of the callosal body produced an inversion of one hemisphere dominance. In the callosotomized animals binocular stimulation enhanced the asymmetry. It is more stable in the cat visual cortex than in rats.

Animals

The development of N-methyl-D-aspartate receptors in cat visual cortex.

During a critical period of early postnatal development, the visual cortex of kittens is susceptible to experience-dependent modifications of neuronal response properties. Recently, the activation of N-methyl-D-aspartate (NMDA) receptors has been identified as an indispensable prerequisite for the induction of such modifications. We therefore investigated developmental changes in the density and distribution of NMDA receptors and questioned whether these showed a relation to the time course of the critical period. We determined the proportion of [3H]glutamate binding sites that were displaced by the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) on 10-microns-thick cryostat sections of the primary visual cortex. The overall density of APV-sensitive [3H]glutamate binding sites increased dramatically between the second and the fourth week and stayed at this level throughout the critical period. Towards the end of the critical period, these binding sites decreased and finally reached adult values that were slightly above those of 2-week-old kittens. APV-sensitive binding sites were present in all cortical layers of the age groups investigated. While the general pattern of developmental changes was similar in all layers, slight differences existed in the time course. These observations are compatible with the notion that NMDA receptor activation is required for the expression of use-dependent change of response properties in the kitten visual cortex. Furthermore, they suggest as a possible reason for the decline of malleability towards the end of the critical period the reduction of NMDA receptors.

2-Amino-5-phosphonovalerate

The distribution and ontogenesis of [3H]nicotine binding sites in cat visual cortex.

In vitro autoradiographic techniques using [3H]nicotine were used to characterise nicotine binding sites in developing kitten visual cortex. These binding sites in adult animals have a Bmax of 3.91 fmol/mg protein and a Kd of 4.40 nM. Displacement experiments indicate that [3H]nicotine binds to a nicotinic receptor site that is similar to central nicotinic sites described by investigators in other mammals. The number of binding sites increases during postnatal development, peaking near 60 days of age and levelling-off thereafter. There is no evidence for large changes in affinity during postnatal development for this binding site. [3H]Nicotine binding sites are densely concentrated in layer IV in the visual cortex of adult animals, with sharply reduced binding outside of cortical areas 17 and 18. This laminar pattern does not change during postnatal development, but an increase in the number of binding sites in layer IV as well as in layers I and VI occurs during early postnatal life. These binding sites disappear when extrinsic cortical inputs are severed. However, they survive when neurons in the visual cortex are selectively destroyed with a cell-specific neurotoxin. Unilateral destruction of the lateral geniculate nucleus eliminates [3H]nicotine binding sites in the visual cortex ipsilateral to the lesion, suggesting that they are located presynaptically on the terminals of lateral geniculate nucleus afferent fibres. The laminar pattern of binding of [3H]nicotine during early development of the visual cortex is complimentary to that for muscarinic acetylcholine receptors. These latter receptors redistribute during postnatal development becoming less prominent in layer IV at the same time as the [3H]nicotine binding sites are increasing in number in this layer. For a short period of time at the height of the critical period for cortical plasticity, both populations of binding sites are located in layer IV.

Animals

Electrophysiological properties of embryonic neocortex transplants replacing the primary visual cortex of adult rats.

Solid pieces of the occipital neocortex derived from 17-day rat fetuses were placed in a cavity formed by complete unilateral aspiration of the primary visual cortex in adult rats. Vital labeling of the brain with bisbenzimide was used to differentiate grafts from the host brain tissue. 2 to 10 months after operation electrophysiological experiments were performed in which neuronal activity and field potentials in transplants were recorded in response to sensory and electrical stimulation of the host brain. This study shows that in a large portion of the transplants (14 out of 25): (1) the majority of neurons (183/270) are controlled by visual stimuli and many of them respond to electrical stimulation of the lateral geniculate body (53/62) and the homotopic sites of the contralateral neocortex (28/62); latencies of these responses are within the ranges typical of the normal visual cortex; (2) there is a topical representation of the visual field on the transplants; (3) receptive field sizes, the preference to stationary flashes or to moving visual stimuli and the temporal response pattern of the grafted neurons are similar to those of the primary visual cortex. However, the field potentials evoked visually were recorded only in part of the transplants (8/14) which revealed clear neuronal visual responses, and field potential depth profile differed from that in visual cortex in situ. The functional organization of the transplants remained unchanged throughout the long-time testing. Taken together, these results suggest that after primary visual cortex removal, fetal neocortex transplants may be able to replace functionally the damaged neural circuitries of the host brain.

Animals

GABA immunoreactive neurons in rat visual cortex.

An antiserum to gamma-aminobutyric acid (GABA) was used in a light and electron microscopic immunocytochemical study to determine the morphology and distribution of GABA-containing neurons in the rat visual cortex and to ascertain whether all classes of nonpyramidal neurons in this cortex are GABAergic. The visual cortex used for light microscopy was prepared in such a way that the antibody penetrated completely through tissue sections, and in these sections large numbers of GABA immunoreactive neurons were apparent. The labeled neurons could be identified as being either multipolar, bitufted, bipolar, or horizontal neurons. In layers II through VIa, GABA immunostained cells were distributed uniformly and accounted for approximately 15% of all neurons, but in layer I all neurons appeared to be immunostained. Electron microscopy of GABA immunostained visual cortex prepared to ensure good fine structural preservation confirmed the presence in layers II through VIa of numerous immunoreactive bipolar neurons, both small and large varieties, as well as multipolar and bitufted neurons. Additionally, electron microscopy reveals that astrocytes are frequently GABA immunoreactive. From a correlated light and electron microscopic evaluation of neurons in GABA immunostained visual cortex, it was possible to confirm which kinds of neurons are GABAergic and what proportion of the neuronal population they represent. Thus, from an analysis of some 950 neurons, it was found that pyramidal neurons were never immunoreactive and that except for 20% of the bipolar cell population, all examples of other types of nonpyramidal neurons encountered in this material were GABA immunoreactive.

Animals

The structure and symmetry of simple-cell receptive-field profiles in the cat's visual cortex.

Receptive fields of simple cells in the cat visual cortex have recently been discussed in relation to the 'theory of communication' proposed by Gabor (1946). A number of investigators have suggested that the line-weighting functions, as measured orthogonal to the preferred orientation, may be best described as the product of a Gaussian envelope and a sinusoid (i.e. a Gabor function). Following Gabor's theory of 'basis' functions, it has also been suggested that simple cells can be categorized into even- and odd-symmetric categories. Based on the receptive field profiles of 46 simple cells recorded from cat visual cortex, our analysis provides a quantitative description of both the receptive-field envelope and the receptive-field 'symmetry' of each of the 46 cells. The results support the notion that, to a first approximation, Gabor functions with three free parameters (envelope width, carrier frequency and carrier phase) provide a good description of the receptive-field profiles. However, our analysis does not support the notion that simple cells generally fit into even- and odd-symmetric categories.

Animals

Surgical undercutting prevents receptor redistribution in developing kitten visual cortex.

Recent studies have shown that several receptor populations in cat visual cortex undergo alterations in their laminar distributions during postnatal development (Shaw et al., 1984a,b; 1986b). These redistributions occur during the first few months of postnatal life, coincident with the physiologically defined critical period for cortical plasticity. In the present communication, we demonstrate that receptor redistributions can be prevented from occurring, or progressing once started, by surgically isolating the visual cortex at appropriate postnatal ages. These data suggest that the maturation of the chemical circuitry of the visual cortex is dependent on factors of extrinsic origin.

Animals

Morphology of single, physiologically identified retinogeniculate Y-cell axons in the cat following damage to visual cortex at birth.

It has been reported previously that neurons in the dorsal lateral geniculate nucleus (LGN) of cats with neonatal damage to visual cortex (KVC cats) have receptive fields that are abnormally large and that the receptive fields of these neurons sometimes do not appear to conform to the normal retinotopic order in the LGN. A primary aim of this study was to determine if these physiological abnormalities are related to inappropriate patterns of retinogeniculate connections. We therefore have analyzed the terminal arbors of retinogeniculate axons in adult cats that had received a lesion of visual cortex (areas 17, 18, and 19) on the day of birth. Single retinogeniculate axons were characterized physiologically and injected intracellularly with horseradish peroxidase. Consistent with earlier reports that neonatal removal of visual cortex results in a retrograde loss of retinal X-cells, all of the retinogeniculate axons that we recorded were from Y-cells. While the visual responses of these Y-cell axons were normal, the morphology of their terminal arbors in the LGN was abnormal. Retinal Y-cell axons in KVC cats have terminal fields in the A laminae of the LGN that are as large or larger than those of normal Y-cells. However, since the LGN in KVC cats is severely degenerated, single Y-cell arbors occupy a proportional volume of the LGN that is 12 times greater than normal. Thus an early lesion of visual cortex produces a severe mismatch between retinogeniculate axon arbor size and target size. Also, despite the normal size of retinogeniculate axon arbors in KVC cats, the number and density of terminal boutons are greatly decreased. Thus our morphological results suggest that the unusually large receptive fields of LGN cells in KVC cats and the relative lack of retinotopic precision in the LGN are due, at least in part, to anomalies in the relative size and distribution of retinogeniculate axon arbors that develop after neonatal removal of visual cortex.

Animals

Source of cholinergic input to ferret visual cortex.

The source of cholinergic input to ferret visual cortex was investigated with a combination of retrograde transport of horseradish peroxidase and choline acetyltransferase immunohistochemistry. Cholinergic projections to ferret visual cortex arise from basal forebrain cells in the septum, diagonal and nucleus basalis magnocellularis; the largest contribution comes from cells in the caudal part of the nucleus basalis magnocellularis. There is no discernible source in the brainstem.

Afferent Pathways

Cerebral metabolism and patterned visual stimulation: a positron emission tomographic study of the human visual cortex.

We studied the impact of visual stimulation upon cerebral metabolism in normal young men using FDG-PET. Results obtained from subjects receiving patterned visual stimulation while performing an ocular fixation task were compared with results from ocular fixation alone. Visual stimulation in the macular region of either hemifield produced significant increases in metabolism of the contralateral posterior striate cortex. Visual stimulation induced highly significant asymmetries in metabolism of the prefrontal and inferior parietal cortices. Metabolic activation in extrastriate areas tended to be right-sided. These findings support the classic notion of retinotopic organization within the primary visual sensory cortex. They also indicate that the patterns of cerebral metabolism are not equivalent between the two cerebral hemispheres. This latter finding suggests that in humans the right cerebral hemisphere may be specialized for visual processing.

Adolescent

Retinotopic organization of human visual cortex mapped with positron-emission tomography.

The retinotopic organization of primary visual cortex was mapped in normal human volunteers. Positron-emission tomographic measurements of regional cerebral blood flow were employed to detect focal functional brain activation. Oxygen-15-labeled water, delivered by intravenous bolus, was used as the blood flow tracer to allow multiple stimulated-state (n = 5) and control-state (n = 3) measurements to be acquired for each of 7 subjects. Responses were identified by applying a maximum-detection algorithm to subtraction-format images of the stimulus-induced change in cerebral blood flow. Response locales were described using a standardized system of stereotactic coordinates. Changes in stimulus location (macular, perimacular, peripheral, upper-field, lower-field) caused systematic, highly significant changes in response locale within visual cortex. Discrete extrastriate visual responses were also observed.

Adult

Fibre divergence in the distal optic radiation: possible basis of functional plasticity in adult primate visual cortex.

The precision of retinotopy in primate visual cortex is commonly thought to result from highly ordered arrangement of fibres in the visual pathways. However, rigid point-to-point representation is hardly compatible with findings of a substantial reorganization of visual cortical maps after peripheral and central lesions. Such observations could be accounted for by divergence in the optic radiation. To explore the hypothesis of fibre divergence, we made small knife cuts in the distal optic radiation of macaca fascicularis. After subsequent axonal tracing by injecting WGA-HRP into lateral geniculate nucleus, we studied the course of distal fibres in white matter. The amount of divergence was assessed by measuring, relative to the prevailing fibre course, length and orientation of labelled fibres between lesion and entry into cortex. Lesion sizes between 1 mm to 3 mm did not result in any detectable diminution of terminal labelling in layer IVC of striate cortex. Individual labelled fibres were found to diverge symmetrically from both sides into the gap distal to the lesion. Divergence starts at a distance of about 3 mm before cortex. At the white matter boundary, less than 10% of all fibres still retain the original direction, with the remaining fibres taking any other orientation without preference. We estimate that this corresponds to a divergence of visual afferents encompassing about 6-10 mm of cortical distance, if intracortical arborization of terminal fibres is taken into account. Possible consequences for functional plasticity in the adult primate visual cortex are discussed.

Animals