Formation of cognitive structures in conditioned-reflex behavior in monkeys: Relationship with type of visual information.

The characteristics of learning processes and long-term memory (LTM) were studied in rhesus macaques discriminating visual stimuli (geometrical figures of different shapes, sizes, and orientations, and with different spatial relationships between image components). Trained monkeys were tested for the ability to perform invariant recognition after stimulus transformation, i.e., changes in size, shape, number of objects, and spatial relationships. Analysis of behavioral characteristics (correct solutions, refusals to decide, motor response times) revealed differences associated with the type of visual information. When monkeys discriminated between black and white geometrical figures of different shapes and orientations, as well as black-and-white figures with different shapes or orientations, the learning time was short and transformation of the stimuli had no effect on correct solutions: there was complete transfer of learning. When monkeys discriminated figures of different sizes or complex images with different spatial relationships, the learning time was significantly greater. Changes in the size and shape of figures led to significant reductions in correct solutions and significant increases in refusals to solve the task and in motor reaction times. Invariance of discrimination in this case appeared after additional training. The results obtained here showed that in conditioned reflex learning, the sensory processing of stimuli has the result that discriminatory features are formed in LTM, i.e., cognitive structures (functional neurophysiological mechanisms), these supporting the classification of visual images. The temporal conditioned link of the executive reaction is established with these. Their formation is determined by the type of sensory information and the existence in LTM of separate subsystems for spatial and non-spatial information.

[Forming of the visual cognitive structures in the monkey conditioned-reflex behaviour: the dependence on the sensory information].

In monkeys, changes in size and shape of figures led to a significant decrease of correct solutions in training and a considerable increase of refusals from solution of tasks as well as the time of their motor response. The invariance of differentiation in this case was achieved after additional training. The data obtained show that, based on the stimulus sensory processing in conditioned-reflex training, in the long-term memory some differentiating signs are formed: the cognitive structures (the functional neurophysiological mechanisms) maintaining the classification of visual images. With these structures, temporary conditioned connection will be established. Their formation will be determined by the type of sensory information and provided for by existence in the long-term memory of separate subsystems for spatial as well as non-spatial information.

[Heterochromatin characteristics in hippocampal neurons of rats with different excitability of the nervous system under conditions of posttraumatic stress disorder modeling].

Two lines of rats, selected according to the excitability of nervous system to the action of an electric current, served as the model objects to study the changes of heterochromatin characteristics in neurons of hippocampus (area CA3) 24 hours, 2 weeks, 2 and 6 months after exposure to prolonged emotional painful stress. It was shown that exposure to stress caused changes in the area, occupied by heterochromatin, only in rats with low-excitability: it was decreased 24 hours, 2 weeks and 2 months following the stress, while it was increased after 6 months as compared to control values. Thus, it was demonstrated for the first time that long-term modifications of heterochromatin structural characteristics of neurons in hippocampus (area CA3) could depend on genetically determined functional state of the nervous system.

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.

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

Processes of novelty learning and keeping the results in Alzheimer's disease in two groups of rhesus-monkeys (three monkeys in each group), were studied: following neurotoxins administrati- on (I group) and saline administration (II group). In two months after the injections (the C1 stage), considerable differences between the groups were revealed in the task of differentiation among contour shapes. For the I group monkeys the learning was difficult: the correct decision making did not reach 85 %, and the probability of refusing to make a decision increased. For the II group monkeys the learning characteristics were not disturbed. In six months after the injections (the C3 stage) the differences between the groups in the task of differentiation among new stimuli (heads of two monkeys) remained at the same level. When studying characteristics of the operative memory associated with keeping the learning results achieved at the C1 stage, a considerable worsening of these characteristics was revealed: diminishing of the correct decision making probability at the C1 stage (actually to the level of 0.5), increase in the probability of refusing to make a decision. The structural-functional organization of interaction between sensory and cognitive processes in learning and keeping the information in the operative memory, is discussed in association with the control of motivation and attention system and the role of the cortex associative areas.

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.

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.

Functional characteristics of the associative areas of the cortex involved in visual information discrimination learning processes in monkeys.

Experiments on three groups of rhesus macaques (intact and with bilateral removal of field 7 and the sulcus principalis) were performed to study the functional characteristics of the associative areas of the cortex while the monkeys learned visual discrimination. Significant differences in learning processes associated with removal of structures and the properties of the stimuli were seen in all animals, in the form of different types of learning curves. As compared with intact monkeys, removal of field 7 had no effect on learning processes for images with properties such as spatial frequency, color, and animal images, though there was a significant worsening in the characteristics of learning during visual discrimination of spatial relationships between objects. Learning processes became unstable, the number of peaks and troughs on learning curves increased, and as a result the training periods were significantly lengthened and 85% of the animals were unable to achieve the learning criterion. Removal of the sulcus principalis significantly worsened the characteristics of discrimination of the sizes of geometric objects, the spatial relationships between them, and stimuli of different colors. The stable reaction time and the probability of refusal in most cases also increased for monkeys of both these groups. Cluster analysis based on the quantitative characteristics of learning processes, despite individual differences between the monkeys, demonstrated a tendency for stimuli to be separated into classes corresponding to different types of information. These data show that the result of sensory processing is that several (at least three) functional visual information flows are generated and that different areas of the cortex deal with these different flows.

Characteristics of interphase chromatin in hippocampal neurons in rats with different excitability of the nervous system exposed to stress at different time of the day.

The structural (number and area of chromocenters) and optical (relative optical density of chromocenters) characteristics of condensed chromatin in hippocampal CA3 neurons in rats differing by excitability of the nervous system (intact and exposed to short-term emotional painful stress) depended on the time of the day and genotypical characteristics of the experimental animals. The detected changes were independent, which attests to specificity of mechanisms determining these features and/or can be attributed to structural and functional heterogeneity of condensed chromatin (heterochromatin, euchromatin, etc.).

Organization of working memory processes in monkeys: the effects of a dopamine receptor agonist.

The effects of the dopamine receptor agonist agroclavin on cognitive processes associated with mechanisms of visual recognition and long-term and working (short-term) memory were studied in delayed visual differentiation and delayed spatial selection tasks in monkeys (rhesus macaques). Measurements made before and after p.o. pharmacological treatment with this agent were used to identify the p.o. dose (5 mg/kg) inducing a significant effect. The psychotropic effect of agroclavin, which induced cognitive dysfunction, was present in all the monkeys studied to one extent or another. Behavioral criteria were: the probability of correct solutions of the visual differentiation task, the probability of refusals to resolve the task, and the time taken for correct motor responses. Despite individual differences in these behavioral characteristics in monkeys, significant changes due to agroclavin were consistently evident in all animals. There was a reduction in the probability of correct solutions, due to worsening of the characteristics of short-term memory; most monkeys showed increases in the numbers of refusals to solve tasks and increases in the time for correct motor responses during these solutions. In fact, all monkeys showed no increases in the number of erroneous solutions in visual differeniation and spatial selection tasks without delays, though in most cases there were increases in the time taken for correct motor reactions and the number of refusals to solve tasks. Data were obtained indicating that the effect of agroclavin was not uniform with respect to different types of visual information. The possible structural-functional organization of processes underlying working memory is discussed on the basis of the conclusion that the behavioral characteristics studied here reflect different components of cognitive processes realized by structures with different functional properties and different locations.

The adaptive effects of hypoxic preconditioning of brain neurons.

Prophylactic transient hypoxia (preconditioning) increased neuron resistance to subsequent induction of severe hypoxia. Published data and results obtained by the authors on the molecular-cellular mechanisms of hypoxic preconditioning are presented. The roles of intracellular signal transduction, genome function, stress proteins, and neuromodulatory peptides in this process are discussed. The roles of glutamatergic as well as calcium and phosphoinositide regulatory systems and neuromodulatory factors as components of "volume" signal transmission are analyzed in hypoxic preconditioning-associated induction of functional tolerance mechanisms against the acute harmful effects of hypoxia on neurons in olfactory slices.

[Disorders of cognitive processes in simulation of Alzheimer's disease in monkeys]. / Narusheniia protsessov rabochei pamiati i priniatiia reshenii u obezian pri modelirovanii bolezni Al'tsgeimera.

Two groups of monkeys were learned to differentiate stimuli with different types of information and to make a spatial choice. Characteristics of the operative memory were revealed in the delayed differentiation tasks prior to and after administration of p75-saporin (I group) and saline (II group). For the first time the Alzheimer disease in monkeys was shown to entail a deficit of operative memory due to disorders in the sensory and cognitive components of the memory. The degree of reduction of the correct decision making was shown to depend on the delay duration and the type of visual information. Following the saline administration, no significant changes occurred in the monkeys (II group). The data obtained suggest that structural-functional organisation of the cholinergic and noradrenergic mechanisms predetermining the sensory processing, differs from those involved in decision-making.

[Interaction between sensory and cognitive processes in visual recognition: the role of the associative areas of the cerebral cortex]. / Vzaimodeistvie sensornykh i kognitivnykh protsessov pri zritel'nom uznavanii: rol' assotsiativnykh oblastei kory golovnogo mozga.

Monkeys were taught to differentiate stimuli with different types of information and to perform a spatial choice. Development of Alzheimer's disease in experimental monkeys entailed a deficit of operative memory, a considerable enhancement of entropy related to correct decisions. In control monkeys, no significant changes of these characteristics occurred. In monkeys, following a bilateral removal of the sulcus principalis, the 7th field, or both, the operative memory deficit was also determined by two components. The specifics of disorders in the operative memory due to Alzheimer's disease suggest that cholinergic mechanisms determining the sensory processing differ from those involved in decision-making. The structural-functional organization of interaction between sensory and cognitive processes controlled by the motivation and attention system, is discussed.

[Functional specifics of cortical associative regions participating in learning to differentiate visual information in monkeys]. / Funktsional'nye osobennosti assotsiativnykh oblastei kory, uchastvuiushchikh v protsessakh obucheniia obez'ian razlicheniiu zritel'noi informatsii.

In 3 groups of monkeys: intact, those with their 7th field bilaterally removed, and those with bilateral removal of the sulcus principalis, functional specifics of the cortex' associative areas were studied. Removal of the 7th field practically does not affect processes of training for images with such features as spatial frequency, colour, and images of animals, but considerably impairs the learning characteristics in visual differentiation of objects' size and spatial interrelationships among objects. Removal of the sulcus principalis considerably impairs the characteristics of differentiation of objects' size and spatial interrelationships among them, as well as differently coloured stimuli. In both these groups, the stable motor response term and the probability of refusal increase. The data obtained suggest that the sensory processing results in forming a few (at least three) functional visual informational flows with which different cortical areas operate.

[Adaptive effects of hypoxic preconditioning in brain neurons]. / Adaptivnye éffekty gipoksicheskogo prekonditsionirovaniia neironov mozga.

A preventive short-term hypoxia (preconditioning) increases neuronal resistance against subsequent strong hypoxic effects. Literature review and authors' own data on molecular-cellular mechanisms of the hypoxic preconditioning, are presented. Participation of intracellular signal transduction, genome, stress-proteins, and neuromodulating peptides in this process, is discussed. The role of glutamatergic as well as calcium and phosphoinositide regulatory systems and neuromodulating factors as the components of a "volume" signal transmission are analyzed in hypoxic precondition-associated induction of functional tolerance mechanisms against acute harmful effects in neurones of olfactory slices.

[ I P Pavlov principles of the higher nervous activity--a reliable basis for modern cognitive physiology]. / Printsipy vysshei nervnoi deiatel'nosti I P Pavlova--nadezhnyi fundament sovremennoi kognitivnoi neirofiziologii.

The paper shows that formulated by I. P. Pavlov principles of higher nervous activity are quite fruitful even today in investigations into the problems associated with contemporary new physiological trends as, for instance, cognitive processes. Special attention is paid to study of the principles of neurophysiological organisation of the mechanisms carrying out analysing and synthesising activities. I. P. Pavlov was the first to indicate the important role of frontal cortex in these processes.

Neurophysiological correlates of delayed visual differentiation tasks in monkeys: the effects of the site of intracortical blockade of NMDA receptors.

A delayed visual differentiation task using stimuli of different colors was used in rhesus macaques to study the characteristics of visual recognition, short-term memory, and the responses of neurons recorded simultaneously in the visual and prefrontal areas of the cortex, along with their relationships with the site of intracortical (fields 17 or 46) perfusion of the glutamate receptor antagonist 2-amino-5-phosphonovaleric acid (APV). The behavioral characteristics and spike activity of individual cells in cortical fields 17 and 46 were recorded before and after perfusion with APV and after washing away of traces of APV. Multifactor dispersion analysis showed that the effect of APV in monkeys consisted of decreases in the probability of correct responses, leading to a decrease (two-fold) in the duration of short-term storage of information and a significant increase in the motor reaction time. The probability of correct solutions depended on the site of APV perfusion in the cortex, while the motor response time was independent of the perfusion site. Perfusion of field 46 with APV, unlike perfusion of field 17, altered the spike activity only of neurons in the prefrontal cortex, while no significant changes were seen in the neuron activity of the visual cortex. The actions of APV were accompanied by significant desynchronization of neuron activity in these two areas as compared with the level of synchronization in normal conditions; after traces of APV were washed away, the extent of desynchronization decreased. The neurophysiological correlates of cognitive dysfunctions associated with degradation of visual recognition and short-term memory due to modification of glutamatergic structures by blockade of NMDA receptors are discussed.