Head of Laboratory – Dr.Sc. (Mathematics) Alexey Chernavsky

Tel.: (095)209-42-25, (095) 952-33-03; E-mail: chernav@iitp.ru

The leading researchers of the laboratory include:

The general theme of the scientific work in the laboratory is: analysis of the information processes in cellular systems and in motor control. The main directions of theoretical researches in this realm: developmental biology (analysis of principles for the realization of genetic information in the developmental systems), neurobiology (neural communication and biochemical modulation in neural centers), motor control (study of geometry of manipulative space and of control goal-directed moving). Also some new bioinformatical principles are worked out including the building of computerized system for the analysis of expert analysis.

Developmental biology. Dr. Bozhkova’s group studies the developmental mechanisms of spatially ordered cell differentiation (the mechanisms of pattern formation in development). There was shown that in addition to recently broadly studied genetic programming in development the information that reaches cells by means of intercellular communication and by high permeable gap junctions, in particular, is of great importance. It was revealed that the properties of permeability and selectivity of gap junction channels have more wide range of variations in different cells than it was proposed earlier. The connection of these properties with the future fate of cells in development was shown. It was supposed that information transmission through gap junctions allows to homotypical cells to maintain their initial potencies and to stabilise their functions. The development of computer model of morphogenesis with participation of gap junctions with different permeability continues. Its kernel is formed by the autowave process such as that was observed in the embryonic cells experimentally after the activation by second messenger inositol-1,4,5-trisphosphate. The model is based on the suggestion that IP3 and its derivatives involved in three-component phosphatidylinositol cycle differently penetrate via gap junctions of different cell types. As the results of the modelling it was shown that the parameters of activation of this cycle and the ratio of the diffusion coefficients of its components essentially influence on the rate and amplitude of autowave process. The working-out model is a part of more general model of current information processing in cells where massive protein complexes are transformed by more motile and small messenger molecules that can be transported through both the plasmatic membrane and the intercellular junctions.

The properties of the plasmatic membranes have different important roles in the cell processes including pathological ones. The fusion of cell membranes induced with proteins of baculovirus and virus of grippe was studied in details by I.P.Plonsky. Leaning upon his improvement of the conventional method for the fusion study he has shown that the properties of the initial fusion pore are determined with the fusion proteins and not by the mechanical characters of the membranes depending on their chemical composition. (In collaboration with the Laboratory of Cellular and Molecular Biophysics, National Institutes of Health, USA).

Communication between cells through the gap junctions in embryo, the important developmental factor, was studied also by D. A. Voronov on different species of nematodes and in different stages of cleavage. The existence of connection through the gap junctions was shown electrophysiologically and the dimension of their channels was studied using fluorescent probes of different molecular weight. It is proven that in nematodes the early stages of development are evolutionary very flexible, but at the course of embryonic development of different nematode species the resemblance of embryos is progressively increased up to the uniform morphogenetic stages. This empirical principle is in an obvious contradiction with the Haeckel’s biogenetic law but it can be interpreted using the modern modification of this law such as the “hourglass” model of Duboule (1994).

On the marine mollusk Clione the studies are initiated by Y. V. Panchin of the mechanisms of neuronal regeneration and recognition. The unique methods are worked out permitting to investigate the selective determination of synaptic contacts between neural cells in conditions of cultivation separate neurons and neuronal tissue. In particular a method is developed for transplantation of separate identified neurons from one to another neuron system. Some genes of proteins needed for formation of neural connections are separated from identified neurons, cloned and characterized. The homologues of these genes may have important roles in neural systems of vertebrates and humans in norm and pathologies.

Neurobiology. The neural system, a base of informational interaction of manycellular animals, was studying in the laboratory at different levels.

In the perennial work of a collective guided by Y. I. Arshavsky and Y. V. Panchin the neural system of a marine mollusk Clione limacina was studied in details. The authors leaned upon the original method of isolating ganglia and separate neurons keeping the tie with the central system conserved. The different systems were investigated mainly those which control movements. In the last years the neural base for the posture stabilization in the gravitational field. It is generated with the reflexes initiated from the activation of the receptor cells of statocyst and mediated with interneurons which excite motoneurons of tail and wings.

The close investigation of neuronal activity in this system was put together with the behavior activity of the animal, which move in water in different directions and in different orientations. Some groups of neurons were separated which are responsible for definite reactions, the correspondence of tail and wings movements ensuring the stability of the normal up-head posture as well as its inverting under some conditions. In particular it is generated with the temperature increase, when the mollusk must sink in the cold layers of water.

Resulting inference was that the posture control system in Clione is not a hardwired network; it can be modified to such an extent that a nearly new network is formed with reversed responses to the same gravitational input.

Dr. I. A. Keder-Stepanova's group studies the organisation of the respiratory rhythm generator.

A model of this system was proposed. The question has arisen, how this system is forming in the onthogenesis and how the properties of its neurons change. It was shown that the original automatic rhythmical activity of the lock kind disappears in later studies of the onthogenesis. The experiments were carried out on the newborn medulla slices in the first 12 pn days . During first week there are burst activity of neurons with different period of the burst into the same slice. The pacemaker burst activity disappeared at 7-8 days. Only continuous discharges were observed after this time.

Together the his to-morphological study was carried out of the neurons. It is shown that the automatism disappears in time of the full development of sprouts in the nucleus. Development of neuron structures and their connections during first postnatal week related to GABAa influence and activation of the GABAa receptors. It is likely that there is relation between dendrite arborization, appearance of GABAb receptors and of inhibitory synapses. But it is not clear what is the source of GABA before synaptogenesis.

In a joint research with L .N. Podladchikova and S. N. Markin from A. B. Kogan Research Institute for Neurocybernetics of Rostov State University and with D. C. Wunsch from Texas Tech University, USA an outstanding result in physiology of the cerebellum has been obtained: the first pair of Purkinje cells, which are controlled with the same climbing fiber has been revealed and described in details. The problem has been first formulated in 1978 year in W.L. Dunin-Barkowski's monograph. Active searches for these pairs began since 1993. Now the method for pairs search and the first examples of the record are obtained.

The group of N. V. Samosudova and N. P. Larionova studies the dependence of cerebellum neural network on the disbalance of its principal mediators: L-glutamate and NO. The electron-microscopic study was carried out of the influence of L-glutamate excess in the extracellular medium. One could see that it leads to the damage of the structure and violation of the interaction between the grain cells and genome function. Now one knows that the pathomorphologic changes due to the L-glutamate excess are in groundwork of such diseases as epilepsy, parkinsonism and Alzheimer. NO whose synthesis can go during one of the stage of glutamate cascade may be very toxic. It is cleared up that the membranes of neurons and glial cells are the most sensitive. Also NO mainly perforate the cell membranes and glutamate further their fluidity and lamination.

Together with pathologic changes in the cerebellum neural network both in glutamate and in NO one have remarked also changes which were classified as compensatory. There appear many-row spiral structures around synapses formed with the processes of glial cells and also glial coils around mainly buttons in NO and mainly spines in glutamate. This result is unexpected because principal cerebellum neurons give the opposite reactions to separate use of stuffs which work in norm in a unique glutamate cascade. (In collaboration with Institute of High Neural Activity.)

In the plane of analysis of information processes in invertebrates neural systems Y. M. Burmistrov carries out the study of the CNS work in higher crustacea under some behavior acts. It was worked out a method of the electrophysiological recording of activity of their ventilation appendages It was also carried out the registration and analysis of the electric field emerging during movements of the appendages in different points of the ambient water space. The contemplation of the correlative relations between symmetrical generators of the ventilator rhythm shows on the more complicated behavior control from the higher regions of crayfish CNS than one could suppose after the comparing of behavior and the ventilator function in the same half of body. (Collaboration with the Institute of the High Neural Activity RAS and Institute of the Nuclear Physics of MSU)

Dr. Z. Kh.-M. Khashaev studies the influence of the varied pharmacological media, especially the supertoxicants of the dioxin series, on the biomembrane penetrability . The study goes in collaboration with the Institute of expermental and theoretical biophysics RAS (Poushchino), and Institute of biochemical physics RAS.

Motor control.The systematic experimental study of the pointing arm movements to the remembered targets was made by M. B. Berkinblit and S. V. Adamovich. The experiments were carried out with visually and in different conditions both to healthy subjects of different ages and to parkinsonics. The main methodical procedure consisted in analysis of variation in accuracy, velocity and acceleration. It is shown that humans plan the arm movements to targets given in space visually and kinesthetically separately for three directions. Partly these results were known, but it is first time that they are studied in full generality. The principal distinction is shown of movements to remembered and to actual targets, what is expressed in particular in independence of variable errors from the velocity for movements to remembered targets.

Comparing movements to visually and kinesthetically given targets one has revealed that a) humans are divided into two groups: ones show more high accuracy for visually given targets, others for kinesthetically given targets; b) that the phenomenon of "space contraction" is the consequence of interaction of planning system with vision system. Motor programs of a complex movement are built before the beginning or in the beginning but they are not seamed during the movement from more simple constituents. The different corrections of joint angles, velocity of arm and trunk, accelerations are revealed. The independent planning of arm movement in different directions and independent planning of accuracy and dynamics make one to propose that during planning the parallel and interacted modules are used.

The movements of aged humans was compared with parkinsonics movements. It was found that in patients the integration of afferent signals in different modalities is embarrassed, namely of visual information (both saved in the space memory and actual) with proprioceptive one from the arm. It is also shown that in patient the temporal concordance of arm and trunk movements in pointing with bending of body is damaged. These results give new important information about functions of basal ganglia which suffer in parkinsonism. (In collaboration with Rutgers Univ., USA and Univ.of Montreal, Canada.)

In the work of L. P. Kudina and N. M. Zhoukovskaya the characteristics of separate motoneurons rhythmic was comparing with the timing of after-hyperpolarisation. It permitted to find an indirect but clinically appropriate index of motoneuron "promptitude". The results were used for modeling mechanisms of motor control.

In 1999 the new work was begun with aim to study the inhibition mechanisms in humans which control the rhythmic firing. In particular it is shown that in distinction to artificial conditions of stimulation used earlier during natural motoneural rhythmic activity their reciprocal influence through Renshow cells is little pronounced. This study is part of cooperative work with the Polish Institute of Biocybernetics and Medical Engineering.

In the group of A. V. Chernavsky the experiments with studying psychophysics of the space visual perception were carried out. The statistically reliable inference is that there exist systematical distortions in perception of linear properties of the space. It is shown in the experiment that the lay-out "first divide the segment into n parts, then lengthen one part n times" for even n (= 2,4,...) gives the systematic mistake of diminution, and for odd n (= 3) – inversely, of exaggeration. The flexure of space near the convergence point of right lines in the known visual "fan" illusion. The work was carried out in collaboration with the sector 1.1.

Bioinformatical principles. The acquisition of knowledge is the most important and difficult process of intellectual system developing. It includes the extraction of information, its structural organisation and transmission. The method of structuring the information gathered by professional experts in non-formalised scientific areas is proposed by I. P. Lukashevich. It was used for building the knowledge bases in neurology, neuropsychology and electroencephalography. In the last case the knowledge base was realized as a computer automatic diagnostic system "EEG-EXPERT". The system includes three parallel subprograms. The first one, DIALOGUE represents a description scheme for the visual analysis of EEG which is organized as a questionnaire. In distinction from other systems here the homogeneous in functional meaning EEG-attributes are united in structure blocs which characterize the conditions of human brain and its separate structures. The subprogram REFERENCE permits to have recommendations for description of the level, character and pronouncing of remarked changes. Subprogram INFERENCE automatically forms and represents on display and sends on printer the description of EEG and the conclusion on the brain functional condition. The system is designed (and used) for the practical work in neurological hospitals and policlinics, for learning young specialists and for exploratory goals.

The complex analysis permitted to determine the diagnostic and prognostic criteria for the movement and speech rehabilitation in patients after ischemic insult, to investigate the influence of afferent subcortical conductive paths on the electric brain activity, and also to make the comparative valuation of the child brain in age of 5-8 years in norm and under the retardation of the psychic development. (With participation of the Institutes of Age Physiology and of Correctional Pedagogics, RA Education.)

• Russian Foundation for Basic Research (No. 97-04-48499): (V. P. Bozhkova).
• Russian Foundation for Basic Research (No. 97-04-48324): (W. L. Dunin-Bar-

kowski).

• Russian Foundation for Basic Research (No. 97-04-50759): (E. A. Liberman).
• Russian Foundation for Basic Research (No. 98-04-48836): (D. A. Voronov).
• Russian Foundation for Basic Research (No. 97-15-98035): (L. M. Chai-

lakhyan, V. P. Bozhkova, W. L. Dunin-Barkowski).

• NSF USA: Neurocomputing Opportunities Workshop (W. L. Dunin-Barkowski).