[Development of Meynert cells in cat visual cortex under the conditions of flickering light stimulation].

To examine the effect of rhythmical light stimulation on postnatal development of the visual system, the formation of Meynert cells was studied in area 17 and posteromedial suprasylvian area (PMLS) of kittens reared under the conditions of flickering light stimulation (15 Hz frequency). Profile area of neuronal cell bodies and cytochrome oxidase (CO) activity level were measured in frontal sections of the visual cortex in control (n = 6) and stimulated (n = 6) kittens. Meynert cells located in area 17 and PMLS demonstrated an approximately 37% increase in CO activity in the stimulated animals. At the same time, the profile area of Meynert cell bodies in PMLS was decreased by 20% as compared to that in normal animals. The presence of functional disturbances of Y-conducting visual channel and the possibility of binocular vision suppression in the stimulated animals are discussed.

[Changes of y neuron formation in cat visual system during early postnatal ontogenesis under the influence of binocular rhythmic light stimulation].

To examine the effect of an artificial rhythmic light stimulation on the development of structural and functional organization of Y neurons of cat visual system in the ontogenesis, the distribution of the neurons immunopositive to SMI-32 antibodies was studied in lateral geniculate nucleus (LGN) and posteromedial suprasylvian area (PMLS). Laminar distribution of SMI-32-positive neurons and neuronal body profile area were analyzed in intact animals (n = 4) and in kittens (n = 4) grown under conditions of rhythmic light stimulation with 15 Hz frequency for 4 months. In light-stimulated animals, changes in laminar distribution of immunopositive neurons were detected in both LGN (decline in the percentage of the immunopositive cells in C(M) layer) and in PMLS area (decrease in cell count in layer V). Morphometric analysis has shown the significant reduction of cell body profile area in immunopositive neurons in light-stimulated kittens only in layers III and V of PMLS area. The data obtained suggest that Y channel functional disturbances in light-stimulated animals are caused by the structural and metabolic changes detected in Y neurons.

[Development of primary visual cortex connections with the motion processing center: the role of visual environment].

Development of axonal connections between cat primary visual area 17 and visual motion processing center was studied to investigate cortico-cortical connection plasticity in ontogenesis as affected by an experimental modification of visual environment (flickering light stimulation). By using a retrograde axonal labeling by horseradish peroxidase, a distribution of initial neurons in area 17 that send afferent projections to PMLS (posterior medial part of lateral suprasylvian sulcus) was analyzed. Sixteen 5-week-old and 12-14-week-old kittens, than were reared in normal visual environment or were subjected to a flickering light of 15 Hz frequency, were examined. It was shown that session stimulation by flickering light led to an impairment of normal development of regular organization of the connections between these visual areas including the decrease of labeled surface area and labeled initial neuron density in area 17. The data obtained elucidate the structural bases of cortical mechanisms that underlie motion processing disturbances in kittens stimulated by a flickering light.

[Early ontogenetic development of regular organization of corticocortical connections between visual areas 17 and posteromedial lateral suprasylvian area in the cat].

Early ontogenetic development of cluster organization of corticocortical connections between visual areas 17 and posteromedial lateral suprasylvian area (PMLS) was studied in cat. Retrograde axonal tracer horseradish peroxidase was microinjected into the area PMLS. Labeled initial neuron distribution was analyzed in area 17 in 5- and 12-week-old kittens. A significant increase of the cortical surface area containing labeled neurons together with the decrease in their distribution density were shown between weeks 5 and 12. An analysis of amplitude and phase of Fourier spectra of labeled neuron distribution patterns demonstrated some differences between the kittens of various age groups and indicated the incompleteness of connection cluster organization formation. The temporal morpho-functional features of the development of PMLS zone corticocortical connections, as compared to the other visual cortical areas, are discussed.

Involvement of the sacral parasympathetic nucleus in the innervation of the descending colon and rectum in cats.

Studies in anesthetized (urethane, 1.5 g/kg, i.p.) cats using retrograde transport of horseradish peroxidase addressed the locations and morphometric characteristics of neurons in the sacral parasympathetic nucleus of the spinal cord innervating the descending colon and rectum. Marker solution was injected beneath the serous membrane of the study areas of the large intestine. Transcardiac perfusion with fixative solution was performed 48 h later and frontal sections of the sacral segments of the spinal cord were prepared; these were processed by the Mesulam method (1978). The results showed that these areas of the large intestine receive innervation from neurons in the sacral parasympathetic nucleus located in spinal cord segments SI, SII, and SIII. The largest number of labeled cells was seen in segment SII. The neurons of this nucleus innervating the study areas of the large intestine formed two longitudinally distributed group (a lateral and a dorsal), the cells of which differed in terms of size and the orientation of the long axis. The largest number of labeled cells was seen in the lateral group.

[Morpho-physiological features of the human eye sclera as the key unit in the level of intraocular pressure under normal conditions and in glaucoma].

The results of sclera investigations from the positions of morphology, physiology, biomechanics and control-system theory, are summarized. The morphological evidence was obtained supporting the physiological hypothesis stating that the specific anatomical organization and spatial displacement of elastic fiber-containing scleral layers against one another, are the key elements in formation of the individual level of intraocular pressure (IOP) in man both under normal and pathological conditions. It was shown that the elastic fibers outlined the collagen lamallae in of scleral internal layers. External scleral layer lacked elastic fibers. Scleral elastic fibers are necessary for the functioning of the mechanism of sclera microfluctuations associated with the intraocular fluid accumulation and removal, they are also important for dampening the sudden changes of IOP. Under normal conditions, age-related increase in scleral rigidity is primarily associated with the process of accelerated aging of its superficial non-elastic layers, resulting in the physiological response of the current IOP level elevation. As IOP becomes elevated under normal conditions, the internal elastic fiber-containing scleral layers are increasingly pressed against more rigid external layer. This limits the displacement capacity of internal layers against each other, resulting in the decline of the efficiency of elastic fiber work in dampening the sudden changes of IOP. In the healthy eyes, the process of scleral aging brings to a natural development of ophthalmohypertension, when IOP elevation is physiologically required for the maintenance of the volume microfluctuation mechanism ("scleral respiration"). In glaucoma, the pathological rearrangement of the scleral fibrous structures is observed, resulting in an additional abrupt increase of its rigidity, with the reciprocal significant elevation of the current level of IOP and the amplitude of its jumps. Pathophysiological mechanism of these significant changes in glaucoma remains currently unknown, however, morphological evidence indicates that it is associated with the changes in the metabolic processes in sclera.

Some aspects of the modular organization of the primary visual cortex of the cat: patterns of cytochrome oxidase activity.

The distribution of the enzyme cytochrome oxidase (CO) in continuous series of parasagittal sections from field 17 and frontal sections of the dorsal nucleus of the lateral geniculate body (LGB) from normal kittens and adult cats was studied. In all cats apart from neonates, layer IV showed regularly alternating areas with above-background levels of CO activity ("spots"). There was a significant increase in the contrast of the "spots" from days 13 to 21, which was followed by a significant decrease from days 48 to 93. These changes coincided with ontogenetic changes in the level of visual system plasticity. There were no differences in CO activity between layers A and A1 of the dorsal nucleus of the LGB. It is suggested that the non-uniform distribution of the level of functional activity of neurons in field 17 reflects the formation of columnar cortical structures during the critical period of postnatal ontogenesis.

Parasympathetic innervation of the initial segments of the large intestine in cats.

The locations and morphometric characteristics of efferent parasympathetic neurons in the dorsal motor nucleus of the vagus nerve and the cruciform parasympathetic nucleus of the spinal cord, innervating the area of the ileocecal sphincter and the ascending and transverse segments of the colon, were studied. Horseradish peroxidase solution was injected beneath the serous membranes of these parts of the intestine in urethane-anesthetized cats. After 48 h, animals were subjected to transcardiac perfusion with a fixative mixture and sections of the medulla oblongata and spinal cord were prepared and processed by the Mesulam method. The results showed that all these parts of the large intestine received parasympathetic innervation from neurons in the ventrolateral part of the dorsal motor nucleus, which were uniform in terms of their morphometric characteristics. The number of neurons of this group sending axons to the ileocecal area was greater than the number of neurons innervating the ascending colon. A second group of neurons, which were smaller cells, was located in the same part of the nucleus and innervated the transverse colon. The transverse colon also received innervation from neurons in the cruciform parasympathetic nucleus of the spinal cord.

[Participation of sacral parasympathetic nucleus in the innervation of the descending colon and the rectum in cats].

The localization and morphometric features of the preganglionic neurons of the spinal sacral parasympathetic nucleus innervating the descending colon and the rectum, were studied in cats, anesthetized with urethane (1.5 g/kg intraperitoneally) using the method of retrograde horseradish peroxidase transport. The solution of the marker was injected under the serosa of the indicated areas of the colon. After 48 h the animals were transcardially perfused with a fixative solution. Frontal sections of the sacral spinal segments were prepared and stained according to M. Mezulam's protocol (1978). It was demonstrated that the indicated areas of the colon were innervated by the neurons of the sacral parasympathetic nucleus, located in SI, SII and SIII segments of the spinal cord. The majority of the labeled cells were observed within SII segment. The neurons of this nucleus, which innervated the indicated areas of the colon, formed two longitudinal groups (lateral and dorsal ones), the cells in which differed by their sizes and longitudinal axis orientation. Most of the labeled cells were detected in the lateral group.

[The area centralis of the mammalian retina: morphology and histogenesis].

This review summarises both classical and current literature data on the structure and the histogenesis of the retina of the mammalian eye and, in particular, of its specialized region--area centralis. The review describes the modem concepts of cytoarchitecture of area centralis, as well as the peculiarities of its blood supply, and presents the details of its histogenesis from early embryonic stages to postnatal development.

[Some aspects of modular organization of the cat primary visual cortex: cytochrome oxidase activity pattern].

Distribution of enzyme cytochrome oxidase (CO) activity was studied in a continuous series of parasagittal sections of cortical area 17 and frontal sections of dorsal lateral geniculate nucleus (LGNd) in kittens of different age and adult cats. In all the kittens except the newborns, in layer IV of area 17, regular alternating areas of CO activity, exceeding the background activity ("spots"), were detected. During the period between postnatal days 13 and 21 a significant increase of "spots" contrast took place, while between postnatal days 48 and 93 contrast was significantly decreased. This contrast changes coincided with the dynamics of visual system plasticity during ontogenesis. No differences in CO activity were detected between layers A and A1 in LGNd. It is suggested that non-uniform distribution of functional activity of area 17 neurons reflects the development of cortical columns during the critical period of postnatal ontogenesis.

[Parasympathetic innervation of proximal parts of the colon in cat].

The localization and morphometric features of efferent parasympathetic neurons of the vagus dorsal motor nucleus and of the spinal sacral parasympathetic nucleus innervating the area of ileocaecal sphincter, ascending and transverse colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of the indicated areas of colon. In 48 hours animals were transcardially perfused with a fixative solution. Sections of the medulla oblongata and the sacral spinal cord were stained using Mezulam's technique (1978). It was shown that all the areas of the colon studied received parasympathetic innervation from the neurons of the ventrolateral part of the vagus dorsal motor nucleus, which were uniform according to their morphometric characteristics. The number of neurons in this group, sending their axons to the ileocaecal area, was greater than the number of neurons, innervating ascending colon. Second group of neurons, that was represented by smaller cells, was located in the same part of the nucleus and innervated transverse colon. Transverse colon had an additional parasympathetic supply from the neurons of the spinal sacral parasympathetic nucleus.

Changes in the structure of neuronal connections in the visual cortex of cats with experimentally induced bilateral strabismus.

The spatial distribution of neuronal connections in cortical field 17 was studied in cats with experimentally induced bilateral convergent strabismus on postnatal days 10-14. Horseradish peroxidase was applied microiontophoretically to individual columns of neurons in fields 17 and 18 and retrograde-labeled cells were identified in both hemispheres. Increases and decreases in the extent of intra-hemisphere connections were seen in the mediolateral direction (projections of the horizontal meridian of the visual field). Most columns showed increases in inter-hemisphere connections in this same direction, which may support the more reliable unification of the two visual hemifields. In addition, some columns showed increases in intra-and inter-hemisphere connections in the rostrocaudal direction (projections of the vertical meridian). Thus, bilateral strabismus induced during the critical period of development leads to changes in the structure of both intra-hemisphere and inter-hemisphere connections of individual cortical columns in fields 17 and 18.

Disorders of learning and memory processes in a monkey model of Alzheimer's disease: the role of the associative area of the cerebral cortex.

The processes of learning and storage of the results of learning were studied in a model of Alzheimer's disease in two groups of rhesus macaques (three individuals in each group). Studies were performed after injection of neurotoxins (group I) and physiological saline (group II, controls). Two months after injections (stage C1), learning parameters were studied in monkeys of both groups using a new stimulus discrimination test (filled geometrical figures versus outline figures). There were significant differences between the animals of the two groups. Learning was hindered in monkeys of group I, with significant increases in the learning time (the time to achieve a stable probability of correct responding of 0.85) and in the probability of refusals. Monkeys of group II showed no learning impairment. Animals were trained to discriminate new stimuli (images of two monkeys) six months after injections (stage C3). Learning was impaired in animals of group I, such that learning measures had the same levels as previously; monkeys of group II showed no learning impairment. Analysis of the characteristics of working memory, which is involved in storing the results of new learning, was performed at stage C1; monkeys of group I showed significant degradation of these measures, with a significant decrease in the probability of correct solutions at stage C1 (to a level of 0.5), with some increase at stages C2 (at four months) and C3, along with a significant increase in the probability of refusals, values being similar at all time points. For monkeys of group II, these characteristics showed no degradation. Motor response times at stages C1, C2, and C3 were not different for the two groups of monkeys. The structural-functional organization of interactions between sensory and cognitive processes during learning and the storage of information in working memory are discussed, as is the role of the associative areas of the cortex in these interactions.

[Structural organization of neurons of spinal ganglia innervating the colon].

The localization and morphological features of viscerosensory neurons of sacral spinal ganglia (SSG), innervating the colon, were investigated. In urethane anaesthetized cats, the solution of horseradish peroxidase was injected under the serosa of ascending and descending parts of the colon as well as of the rectum. After 48 hours animals were repeatedly anesthetized and transcardially perfused. Sections of SSG were stained according to Mezulam protocol (1978). All the regions of the colon studied were shown to receive afferent innervation from neurons of SSG SI, SII and SIII. Maximum number of the labeled cells was detected in SSG SII. The intensity of afferent innervation of the colon by the neurons of SSG was found to increase along its length in cranio-caudal direction.

Characteristics of cytochrome oxidase activity in visual system neurons in kittens reared in conditions of flashing illumination.

The studies reported here addressed the effects of flashing (15 Hz) lights on the metabolic activity of visual system neurons in animals reared in condition of crepuscular illumination. Activity of the respiratory enzyme cytochrome oxidase was detected in the cortex of visual areas 17 and 18 and in the lateral geniculate body in kittens. The results showed that kittens subjected to this stimulation, unlike intact kittens and kittens reared in conditions of crepuscular illumination, showed a change in the pattern of cytochrome oxidase distribution in cortical field 17 consisting of the appearance of alternating areas of increased and decreased enzyme activity in layers III and IV. In cortical field 18 and the lateral geniculate body, experimental kittens showed no changes in the cytochrome oxidase activity distribution pattern. It is suggested that flashing illumination leads to disturbance of the balance in activity in the Y and X conducting channels of the visual system.

Interaction of sensory and cognitive processes during visual recognition: the role of the associative areas of the cerebral cortex.

The first part of the present study used a model of Alzheimer's disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimer's disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimer's disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.

Neuronal connection of the cortex and reconstruction of the visual space.

The distributions of retrograde labeled cells in fields 17 and 18 and the fields 17/18 transitional zone were studied in both hemispheres of cats after microiontophoretic administration of horseradish peroxidase into individual cortical columns in fields 17, 18, 19, and 21a. The clustered organization of the internal connections of the cortical fields, the asymmetrical locations of labeled callosal cells relative to the injected columns, and the defined distribution of labeled cells in layers A of the lateral geniculate body suggested that eye-specific neuronal connections support "binding" of the visual hemifields separately for each eye. Application of marker to columns in fields 19 or 21a demonstrated disparate inputs from fields 17 and 18 and the fields 17/18 transitional zone. It is suggested that these connections may support the extraction of loci and stereoscopic boundaries located in the central sectors of the visual space.

Impairments in working memory and decision-taking processes in monkeys in a model of Alzheimer's disease.

Studies were performed on two groups of animals (three monkeys in each). Monkeys of group I received unilateral intracerebroventricular injections of the neurotoxin p75-saporin (the ribosomal toxin saporin bound to monoclonal antibody to the p75NTR receptor), which elicits irreversible degradation of cholinergic neurons in the basal nuclei of Meynert, along with the enzyme dopamine-beta-hydroxylase (DBH-saporin), which impairs the functioning of noradrenergic neurons in the locus ceruleus. Monkeys of group II received injections of sterile physiological saline (0.9% NaCI). Monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids, geometric figures with different colors, different spatial relationships between objects) and perform spatial selection. The characteristics of working memory were identified in delayed differentiation tasks in monkeys of both groups before and after injections. These studies provided the first evidence that the development of Alzheimer's disease in rhesus macaques is characterized by a deficiency of working memory, this being based on impairment of two components of these processes. Impairment of the first in monkeys of group I was minifest in delayed visual differentiation as a significant decrease in correct responses. The extent of decreases depended on the duration of the delay and the type of visual information. Impairment of the second component, associated with decision-taking processes, was characterized by an increase in refusals to take decisions and was independent of the duration of delays and the type of visual information. Monkeys given injections of physiological saline showed no significant differences in these characteristics. The features of impairments in these memory components resulting from the development of Alzheimer's disease demonstrate that the structural-functional organization of cholinergic and noradrenergic mechanisms responsible for sensory processing differ from those involved in decision-taking.

[Changes of the structure of neuronal connections in visual cortex of cats with experimentally induced bilateral strabismus].

The spatial distribution of neuronal connections in cortical area 17 in cats with bilateral convergent strabismus, surgically induced on postnatal days 10-14, was investigated. Single cortical columns of areas 17 and 18 were microiontophoretically injected with horseradish peroxidase and retrogradely labeled cells in both hemispheres were detected. The intrahemispheric connections in area 17 along the mediolateral direction (the projection of visual field horizontal meridian) were found to be either dilated or reduced. For most columns, the interhemispheric connections in this direction were increased, which may provide for more reliable unification of two visual hemifields. Moreover, the extension of intra- and interhemispheric connections in rostrocaudal direction (along the visual field vertical meridian projection) was detected in some cortical columns. Thus bilateral strabismus induced during the developmental critical period, modifies the structure of both of intra- and inter-hemispheric spatial neuronal connections of individual cortical columns in areas 17 and 18.