F. N. Makarov

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.

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-β-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% NaCl). 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 manifest 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.

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.

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.

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.

Development of the Connections of the Primary Visual Cortex with the Movement Analysis Center: the Role of the Visual Environment

The plasticity of visual corticocortical connections during ontogeny in an experimentally altered visual environment (stimulation with flashing lights) was studied by investigating the development of axonal connections between the primary visual cortex (field 17) and the visual movement analysis center in cats. A method based on retrograde axon transport using horseradish peroxidase as marker was used to study the distribution in field 17 of start neurons sending afferent fibers to the posteromedial part of the lateral suprasylvian sulcus in 16 kittens aged 5 and 12–14 weeks in conditions of a normal visual environment or with stimulation with flashing light (15 Hz). Sessions of stimulation with flashing light were found to lead to impairment to the normal development of the ordered organization of connections between these visual areas, with decreases in the area of labeling and the number of start neurons in field 17. These data clarify the structural grounds for the cortical mechanisms underlying impairments to the processing of information relating to the movement of visual objects in stimulated kittens.

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.

Structure of internal interneuronal connections in field 17 of the cat cerebral cortex.

The spatial distribution of horizontal internal connections in field 17 of the cat cortex was studied after microiontophoretic application of horseradish peroxidase to individual cortical columns. Cluster analysis of the distribution of labeled cells in the superficial layers in the tangential plane of the cortex was performed. Field 17 included 7 ± 1 clusters of up to five cells. Clusters were distributed into two layers, separated by 1.2 ± 0.3 mm. The distance between the centers of the clusters forming rows was 0.8 ± 0.3 mm. The spatial characteristics of the grouping of cells sending axons into the cortical column were compared with published data based on optical visualization of the activity of neurons in orientational and eye-dominant columns of the visual cortex. It is suggested that columns in field 17 are associated with 6–8 hypercolumns, though only with a single type of neuron within these hypercolumns, in terms of eye dominance and orientational preference.

DIGITAL PROCESSING OF IMAGES IN PHYSIOLOGICAL STUDIES

Digital image processing is now one of the main instruments in studies of many important questions in a wide range of scientific and economic areas in which the initial data consist of various types of images [3]. Specialized systems for processing and measuring images generally include input-output devices, processing units, and instruments for visualizing the results of processing [1, 2, 9, 13, 14]. Experimental data in many areas of physiology also appear in the form of static or dynamic images, the objects in which or fragments of which can be measured with great precision by processing, this providing new knowledge of physiological mechanisms which is unobtainable by other investigative methods. An Image Processing Center was set up on this basis at the I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, in 1996, with the new aim of developing a novel complex approach to this currently relevant area of study. The main aim of the present article is to accentuate the significance of this important methodological approach, to disseminate information to colleagues working in different areas of physiology, to obtain experimental data in the form of images, the functions of the Center, and to invite collaborative projects. The Center has instruments based on optical, television, and computer systems for input-output and digital processing of microand macroimages.