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Distribution of glial fibrillary acidic protein and vimentin immunoreactivity during rat visual cortex development.

The postnatal maturation of astrocytes in the rat visual cortex was analysed by immunostaining the astroglial proteins vimentin and glial fibrillary acidic protein with poly- and monoclonal antibodies. Vimentin immunoreactivity was present in the visual cortex up to the third postnatal week, whereas immunolabelling first disappeared in the cortical layers and then in the white matter. In the early postnatal period, vimentin antibodies labelled radial glial fibres. After the first postnatal week staining of radial glial fibres gradually disappeared and vimentin immunoreactivity was localized in a few protoplasmic astrocytes in the grey matter and fibrous astrocytes in the white matter. The development of glial fibrillary acidic protein-positive astrocytes was not fully complete until postnatal day 50. Glial fibrillary acidic protein-positive radial glial fibres were present after birth and disappeared towards the end of the third postnatal week. Staining of astrocytes in the white matter and in cortical layers I and VI reached an adult density at postnatal days 8 and 20, respectively. A progressively later development of glial fibrillary acidic protein-positive astrocytes was observed in cortical layers II-V which was completed between postnatal days 47 and 50. In the adult rat visual cortex glial fibrillary acidic protein-positive astrocytes were especially dense in layers I and VI, moderate in layers II/III and V and nearly absent in layer IV and lower layer III. The time course of the loss of vimentin and the gradual appearance of glial fibrillary acidic protein immunoreactivity in the visual cortex is considered as an index of astrocytic maturation and the spatiotemporal sequence of this maturation pattern is discussed in terms of reciprocal neuron-astrocyte interactions during brain development.

Animals

Organization of corticocortical connections in human visual cortex.

Clinical and psychophysical observations indicate that the visual cortex is critical for the perception of color, form, depth, and movement. Little, however, is known about the cortical circuitry that underlies these functions in humans. In an attempt to learn more about these connections, we have traced projections of primary (V1) and secondary (V2) visual cortex in the postmortem, fixed human brain, using the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate as an axonal marker. The results show that V1 makes a forward projection to layers 3 and 4 of V2, and V2 projects back to layers 1, 2, 3, 5, and 6 of V1. Some V2 injections also show an input to layer 4B of V1. Projections to 4B probably originate from cytochrome oxidase (CO)-reactive stripes that we have identified in V2. Differential connections between CO-rich (blobs) and CO-poor regions (interblobs) also exist within V1; blobs are connected to blobs and interblobs are connected to interblobs. The results show that the connections in human visual cortex are similar to those of nonhuman primates and that their organization is consistent with the concept of multiple processing streams in the visual system.

Adult

Evidence for a dopaminergic innervation of cat primary visual cortex.

Experiments have been conducted to determine whether dopamine fulfills the criteria to be considered as a neurotransmitter in cat primary visual cortex. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a neurotoxin with high selectivity for noradrenergic terminals, was administered into kitten cerebral ventricles. Two weeks later, the concentration of norepinephrine in visual cortex was reduced to 15% of control while dopamine and serotonin were not depleted. Receptor binding assays with [3H]SCH 23390 showed that membranes prepared from cat primary visual cortex contain a binding site that has the properties of a D1 receptor. This site was localized by autoradiography to two bands, one in layer VI and the second in upper layers of visual cortex. A dopamine-stimulated adenylate cyclase activity was demonstrated that was inhibited by SCH 23390 but not by alprenolol. Norepinephrine was shown to stimulate adenylate cyclase activity through both a beta-noradrenergic receptor and a D1 receptor. Binding assays with [3H]spiperone indicated that D2 dopamine receptors are absent from cat visual cortex or present in very low amounts. Taken together these results strongly suggest the existence of a dopamine innervation of cat primary visual cortex. The neurotoxin experiments show that some of the dopamine in cat visual cortex is not in noradrenergic terminals while the receptor assays demonstrate the presence of D1 receptors functionally linked to the synthesis of cyclic 3',5'-adenosine monophosphate. The demonstration of a dopaminergic innervation in cat primary visual cortex is also relevant to the interpretation of data on the involvement of catecholamines in developmental plastic phenomena.

Adenylyl Cyclases

Role of visual cortex in interocular alignment.

The role which the visual cortex plays in the development of interocular alignment in the cat was examined by removing this structure bilaterally in 4 groups of subjects. These included (1) kittens 10 to 14 days of age, (2) 10- to 14-day-old kittens in which one eyelid was sutured shut at the same time, (3) normally reared adult cats, and (4) cats dark-reared until 4 months of age. If the cortex is removed in young kittens, interocular alignment appears to develop normally until the kittens are 60 to 80 days of age. At this time, an abrupt change in alignment resulting in incyclotorsion of the optic axes is observed. If binocular vision is prevented in kittens with neonatal visual cortex lesions by suturing one eyelid shut, convergent strabismus and/or incyclotorsion are frequently observed. This characteristic incyclotorsion does not develop if similar lesions are made in adult cats; no significant alterations of eye alignment occur in these animals even after postoperative survival times of more than 6 months. Incyclotorsion characterizes dark-reared cats when they are first brought into the light, but this diminishes with time and may even be replaced by excyclotorsion after the animals spend a few weeks in the light. If dark-reared cats are decorticated on being brought into the light, these changes are largely prevented. Such animals remain permanently incyclotorted relative to normal cats. The results indicate that the visual cortex plays an important role in the development of torsional alignment of the eyes.

Animals

Morphological types of projection neurons in layer 5 of cat visual cortex.

Pyramidal cells in layer 5 of the visual cortex have multiple cortical and subcortical projection sites. Previous studies found that many cells possess bifurcating axons and innervate more than one cortical or subcortical target, but cells projecting to both cortical and subcortical targets were not observed. The present study examines the morphology of cells in cat visual cortex projecting to the superior colliculus, the main subcortical target of layer 5, and cells in layer 5 projecting to cortical areas 18 and 19. The neurons that give rise to these different projections were retrogradely labelled and intracellularly stained in living brain slices. Our results show that cells within each projection group have several morphological features in common. All corticotectal cells have a long apical dendrite forming a large terminal tuft in layer 1. Their cell bodies are medium sized to large, and their basal dendrites form a dense and symmetrical dendritic field. Corticocortical cells in layer 5 have a very different morphology: their apical dendrites are short and they never reach higher than layers 2/3. Their cells bodies are small to medium sized and they have fewer basal dendrites than corticotectal cells. Thus there are two morphologically distinct projection systems in layer 5, one projecting to cortical and the other one to subcortical targets, suggesting that these two systems transmit different information from the visual cortex. Among the corticotectal cells with the largest cell bodies we found some cells whose basal and apical dendrites were almost devoid of spines. Spiny and spinefree corticotectal cells also have different intrinsic axon collaterals and therefore play different roles in the cortical circuitry. While many spiny corticotectal cells have axon collaterals that project to layer 6, spinefree corticotectal cells have fewer axon collaterals and these do not arborize in layer 6. We suggest that the two morphological types of corticotectal cells might be related to functional differences known to exist among these cells. We discuss how the presence or absence of spines affects the integration of the synaptic input and how this might be related to the cells' functional properties.

Animals

Functional consequences of modification of callosal connections by perinatal enucleation in rat visual cortex.

The effects of neonatal monocular enucleation (right eye) on the callosal connections in the rat visual cortex were studied by physiological and morphological methods. Evoked activity was recorded in the left hemisphere, i.e. contralaterally to the enucleated eye. After enucleation, trans-callosally evoked responses were recorded in a widened stripe of the lateral visual cortex. Compared with the controls, the responsive area was expanded laterally and medially, i.e. into the lateral part of the primary visual area and within the secondary visual cortex (lateral part). Within about 0.5 mm of the expansion, the responses did not differ from those recorded in areas with "normal" callosal connections. Morphological evidence is presented suggesting that this expansion of evoked responses with high amplitudes and short latencies corresponds to an extension of callosal connections with a high density of axon terminals in layers two and three. Further medially within the primary visual cortex, callosally evoked responses with low amplitudes and longer latencies were recorded. The main types of unit responses and characteristic interactions between visually and callosally evoked responses are shown and discussed. These results suggest that following neonatal enucleation (1) the callosal connections expand and form functional synapses in the lateral part of the visual cortex, (2) these connections can activate cortical neurons either directly or by mediation of associational connections between the lateral secondary and primary visual cortex areas and (3) callosal connections can interact with visually evoked potentials and unit responses.

Animals

Effect of early visual pattern deprivation on development and laminar distribution of cholinergic markers in rat visual cortex.

In order to evaluate the role of cholinergic cortical mechanisms in the shaping of visual cortical plasticity in more detail the present paper summarizes recent studies on the laminar distribution of muscarinic acetylcholine receptors, choline acetyltransferase, and sodium-dependent high-affinity choline uptake sites during postnatal ontogenesis of the visual cortex of monocularly derived rats using autoradiographic techniques as well as quantitative biochemical methods after separating the different cortical layers by a cryocut technique. The data are correlated to the laminar distribution of cholinergic fibers within the visual cortex as studied by the immunohistochemical visualization of choline acetyltransferase. The laminar distribution of cholinergic receptor binding in the visual cortex changes during ontogenesis. In adult rats, the highest muscarinic acetylcholine receptor density is found in layer I. The activity of the choline acetyltransferase is rather uniformly distributed in all cortical layers. Adult activity values are reached at the age of 25 days. In adult rats the enzyme activity is highest in layer V. In all visual cortical layers the highest 3H-hemicholinium-3 binding to choline uptake sites during the postnatal period studied is already detectable at the age of 10 days, then binding decreases sharply until day 25 at which age it nearly equals the value found in the adult brain. Binding sites exhibit highest density in layers I and IV of the adult rat visual cortex. Monocular deprivation resulted in significant changes in all three parameters studied with different cortical laminae preferentially affected. The data suggest that the normal laminar development of the modulatory function of cholinergic transmission in the rat visual cortex depends on the presence of physiological light stimulation.

Aging

Direct connections of rat visual cortex with sensory, motor, and association cortices.

Each division of rat visual cortex, areas 17, 18a, and 18b, has connections with sensory, motor, and association cortices. These corticocortical connections were sampled using anterograde autoradiographic and retrograde horseradish peroxidase labeling techniques. Area 17 is connected via reciprocal pathways with each division of visual cortex, the posterior one-third of motor area 8, association area 7, and posteroventral area 36 of temporal cortex. It also receives projections from perirhinal areas 13 and 35. Area 18a has reciprocal connections with areas 17 and 18b, a patch in posterior somatosensory area 3, and dorsal auditory area 41. Like area 17, area 18a receives afferents from and projects to the posterior one-third of motor area 8. The connections of area 18a with association cortices are extensive; these regions include parietal areas 7, 39, 40, and 14, posteroventral and dorsal area 36, and perirhinal cortex. Area 18b is connected with areas 17 and 18a, a patch in medial area 3, and dorsal area 41. There are reciprocal projections between area 18b and posterior area 8. As for association cortex, area 18b projects to frontal area 11, area 7, posteroventral and dorsal area 36, and perirhinal cortex. In addition, area 18b receives input from and projects efferents to the dorsal claustrum. Most of the interconnections among areas 17, 18a, and 18b originate from neurons in layers II, III, and V and end in terminal fields in layers I-III and V. In contrast, projections of other sensory, motor, and association cortices to visual cortex originate mainly from neurons in layer V and to a lesser extent from layer II. The reciprocal pathways from visual cortex terminate predominantly in the supragranular layers. In conclusion, these corticocortical pathways provide the basis for cortical visuosensory and visuomotor integration that may aid the rat in the coordination of visually guided behaviors.

Animals

Reinstatement of binocular depth perception by amphetamine and visual experience after visual cortex ablation.

In adult cats with bilateral visual cortex ablation the complete deficit in binocular depth perception, as measured on a visual cliff, was reversed by 4 doses of amphetamine. The amphetamine-induced recovery endured after the amphetamine treatment was discontinued. This enduring recovery of function was not obtained if the animals were housed in the dark during drug intoxication. Therefore, both amphetamine intoxication and visual experience are simultaneously required for recovery of binocular depth perception after visual cortex ablation.

Animals

Cortical activity blockade prevents ocular dominance plasticity in the kitten visual cortex.

Recordings from single units in kitten primary visual cortex show that a reversible blockade of the discharge activities of cortical neurons and geniculocortical afferent terminals by intracortical infusion of the sodium channel blocker tetrodotoxin (TTX) completely prevented the ocular dominance shift that would normally be seen after monocular deprivation. The blockade of cortical plasticity, like the blockade of discharge activity, was reversible, and plasticity was restored following recovery from the effects of TTX. These results extend previous work suggesting involvement of electrical activity at the level of the cortex in the phenomenon of cortical plasticity by demonstrating an absolute requirement for discharge activities in the primary visual cortex.

Action Potentials

Effect of dark rearing on the volume of visual cortex (areas 17 and 18) and number of visual cortical cells in young kittens.

The surface area, total volume, and total number of neurons of areas 17 and 18 in one hemisphere of dark-reared (DR), dark-reared and light-exposed (DRL), and normally reared (NR) kittens were studied at the age of 6 weeks. The thickness of the visual cortex was lower by 13% and 11% (area 17) and by 17% and 16% (area 18) in DR and DRL groups, respectively, when compared with similar cortical areas in NR kittens. The surface area values of area 17 were nearly the same in DR and DRL kittens, both being, however, 37% smaller than in NR animals. The surface area of area 18 was significantly smaller than that of area 17 in each group, and was also lower in DR (by 27%) and DRL (by 21%) groups when compared with the NR group. As a consequence of dark rearing, the numerical density of cortical neurons in area 17 amounted to about double of the value observed in normally reared kittens and was also significantly higher in area 18. The numerical density of nerve cells of DRL kittens fell between the DR and NR groups. The total cortical volume of area 17 was similar in DR and DRL groups but it was by 46% (DR) and by 44% (DRL) smaller than in NR kittens. In each experimental group, the total volume of area 18 was significantly smaller than that of area 17. The cortical volume of area 18 was also smaller than in the NR group by 39% and 34% in DR and DRL groups, respectively. In DR and NR kittens, the total numbers of neurons in areas 17 (DR = 26.4 million, NR = 25.7 million) and 18 (DR = 8.5 million, NR = 9.0 million) were essentially similar. In the DRL groups a significantly smaller number of cortical neurons was found both in area 17 (21.5 million) and in area 18 (6.8 million). It is concluded that, in spite of considerable differences in the cortical thickness, surface area, numerical density, and total cortical volume, the absolute numbers of neurons in area 17 and 18 of visually deprived (DR) and NR kittens do not differ at 6 weeks of age. The main deficit in cortical organization following dark rearing, therefore, appears to be confined mainly to the neuropil, as a result of an underdevelopment of neuronal processes and of depressed synaptic organization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Why spatial frequency processing in the visual cortex?

The nature of redundancy in visual images is discussed and the methods of removing statistical redundancies are considered. It is demonstrated that local spatial frequency analysis is a highly successful method and it is thus argued that this determines the choice of representation of the visual image by the simple cells of the visual cortex.

Humans

Laminar thermocoagulation of the visual cortex in the rat. II. Visual pattern discrimination.

Hooded rats were trained on a series of four visual discrimination tasks in a Y-maze, and subjected to a variety of posterior cortical lesions. In 17 animals this consisted of an extensive aspiration lesion contralateral to a more superficial lesion made by laminar thermocoagulation and centered over the striate area. After operation the animals were tested on the same problem series. The behavioral deficit in this group varied with the extent and depth of the thermal lesion, and six animals with very superficial thermal lesions displayed an isolated difficulty in solving an encircled triangle problem. This deficit seemed to be referable to widespread involvement of supragranular cortex, and specifically of layer I of area striata which receives an input from the nonspecific thalamocortical afferents. The possible influence of various interlaminar projections upon underlying vertically-oriented cell columns as a mechanism for the mediation of 'selective attention' was discussed.

Animals

Effect of electrical stimulation of locus coeruleus on the activity of neurons in the cat visual cortex.

1. We studied the effect of electrically stimulating the locus coeruleus (LC) and iontophoresing noradrenergic antagonists on visual responses and spontaneous activity of individual cells in the cat primary visual cortex. 2. A bilateral projection from LC to visual cortex was demonstrated anatomically, by retrograde labeling using horseradish peroxidase. Where electrical stimulation of both ipsilateral and contralateral LC affected a cortical neuron, the effect induced by stimulating each side was similar. 3. One hundred and two cells were recorded in area 17: 52% of them had their activity suppressed and 36% had their activity facilitated by LC stimulation. The suppressive effect was predominant in cortical layers II + III and IV, whereas most cells in layer V and one-half of the cells in layer VI were facilitated by LC stimulation. This suggests that LC neurons innervate each cortical layer in a different manner. 4. Simple and complex cells were equally sensitive to LC stimulation. For simple cells, the suppressive effect of LC stimulation was dominant throughout all layers. For complex cells, the suppressive effect was dominant in layers II + III and IV, whereas the facilitatory effect was dominant in layers V and VI. 5. The suppressive effect of LC stimulation was blocked by iontophoretic application of beta-adrenergic receptor antagonists and the facilitatory effect was blocked by either alpha- or beta-adrenergic receptor antagonists. 6. Nonselective alpha-, and selective alpha 1- and alpha 2-receptor antagonists suppressed visual and spontaneous activity in almost all neurons tested, suggesting that these receptors are either facilitatory at a postsynaptic site or inhibitory at a site presynaptic to an inhibitory synapse in the visual cortex. 7. beta-Receptor antagonists facilitated activity in 45% and suppressed activity in 36% of the cells tested, suggesting there are both suppressive and facilitatory types of beta-receptors. 8. The effectiveness of alpha- and beta-antagonists on the activity of neurons without LC stimulation also suggested that spontaneously released noradrenaline activated noradrenergic receptors in the visual cortex even in the anesthetized and paralyzed cat. 9. In most cells tested, both alpha- and beta-receptor antagonists exerted effects on single neurons suggesting that endogenous noradrenaline acts on both alpha- and beta-receptors on the same cell. 10. The activation of LC did not improve the signal- (visual response)to-noise (spontaneous discharge) ratio of neurons in the visual cortex. 11. LC seemed to control the activity of each cortical layer differently, by activating different kinds of noradrenergic receptors in different layers.

Adrenergic alpha-Antagonists

[Nuclear and cytoplasmic RNA in visual cortex neurons of adult rats following visual deprivation and photic stimulation].

It has been shown by two-wavelength cytospectrophotometry of gallocyanin-chrome alum-stained sections that visual deprivation in adult rats kept in a complete darkness for 30 days resulted in an accumulation of cytoplasmic RNA by layer V neurons of the visual cerebral cortex and by the cells of the perineuronal neuroglia of this layer. The nuclear RNA content remained unchanged. Stimulation of intact rats with a flickering or constant light induced an increase in the cytoplasmic RNA in these neurons rather than in the nuclear RNA as well as in RNA in their glial satellite cells. Similar light stimulation of the deprived animals gave rise to a complete return of the neuronal RNA to normal with only a slight decrease in the deprivation-induced RNA accumulation by the neuroglial cells. Neither visual deprivation nor light stimulation affected the RNA content in the neurons and neuroglia of layer V of the motor cerebral cortex. Compartmentation of RNA metabolism within the neuronal-neuroglial unit is discussed.

Animals

Changes of drebrin expression in the visual cortex of the cat during development.

The expression of and developmental changes in drebrin were studied in cat visual cortex using immunohistochemistry and immunoblot analysis. Drebrin is a developmentally regulated brain protein which in the chicken has characteristic changes in expression related to developmental stage. A monoclonal antibody (MAb M2F6) raised against drebrin, was found to label the neuropil of the kitten visual cortex in the early postnatal period. At 1-3 weeks of age, the staining was prominent in layer IV of the visual cortex. The immunoreactivity, however, was found to be dramatically decreased around the end of the sensitive period for ocular dominance plasticity (approximately 3 months of age). In the adult visual cortex, almost no immunostaining was observed. These developmental changes revealed by an immunohistochemical method were confirmed using immunoblot analysis. Upon immunoblot analysis after SDS-PAGE of protein from the kitten visual cortex, MAb M2F6 was found to recognize two protein bands with molecular weights of 130 kDa (drebrin E) and 140 kDa (drebrin A). The developmental profile of the intensity of the two bands of the drebin closely parallels in time the postnatal changes in cortical susceptibility to visual deprivation. These results indicate that the expression of drebrin in kitten visual cortex is restricted to the early postnatal period and suggest that it may play an important role in the experience-dependent modification of cortical circuitry during the sensitive period.

Aging

Distribution of parvalbumin immunoreactivity in the visual cortex of Old World monkeys and humans.

The macaque visual system has been frequently used as a model for understanding functional aspects of human vision. There are, however, few studies directly comparing biochemically defined neuronal populations in the visual cortex of the two species. In this study we compared the distribution and morphological features of the parvalbumin-immunoreactive neuronal subpopulation within humans and Old World monkeys (Macaca fascicularis and Macaca mulatta) by using monoclonal antibodies against the Ca2(+)-binding protein parvalbumin (PV), a neuronal marker in the vertebrate cerebral cortex. Characteristic laminar density and distribution of PV is observed, matching that seen with cytochrome C-oxidase and gamma-aminobutyric acid (GABA) immunoreactivity. Thus, parvalbumin is prominent in the layers receiving afferents from the dorsal lateral geniculate nucleus. Terminal fields are rich in layer IVA and IVC and moderate in the blob-region of layer II-III of the monkey cortex. In the human visual cortex only layer IVC displays rich terminal fields. Parvalbumin is present in neurons within all layers of the cortex except layer I. Parvalbumin-immunoreactive (PV-ir) axons occur in different lamellae of the white matter containing axons belonging to association or projection neurons. The estimation of PV-ir neurons, determined for 50 microns-wide columns through the thickness of area 17, shows that the percentage of the total neuron number in area 17 of humans containing PV is 6.8 +/- 2.0%, and in the macaque monkey, 11.5 +/- 2.9%. The perikaryal area of PV-ir neurons varies according to the layer and is comparable in humans (109.3 +/- 40.8 microns2) and monkeys (94.3 +/- 29.5 microns2). However, the relative number of large PV-ir neurons is higher in humans. The immunoreactive product fills the thinnest cell processes and the shape of PV-ir neurons can be easily traced with the aid of a camera lucida. The shape of the neurons is similar in the two species studied, and they probably belong to non-spiny stellate, double-bouquet, chandelier, and basket cell classes. This study shows that parvalbumin acts as a marker for a subpopulation of interneurons in area 17, but it is also present in the geniculocortical as well as in corticocortical pathways. Moreover, the Old World monkey and human visual cortices have a similar, but not identical, distribution of this important calcium-binding protein.

Animals