Education and experience:
1953 - 1959 | Therapeutic and prophylactic Faculty of YSMI. |
1959 | Acting senior fellow of the L. Orbeli Institute of Physiology. NAS RA |
1962 | Junior research of the L. Orbeli Institute of Physiology NAS RA. |
1970 | Ph.D. Thesis "On the neuronal organization of the red nucleus." |
1973 | Senior research fellow at the L. Orbeli Institute of Physiology NAS RA |
1985 to date | Head, Lab. "Physiology of CNS functions compensation" L. Orbeli Institute of Physiology National Academy of Sciences |
1986 | Leading research fellow of the L. Orbeli Institute of Physiology. NAS RA |
1989 | Doctoral Thesis "The mechanisms of synaptic and neuronal organization of the red nucleus." |
1990-1991 | Block program of the USSR “Alarm”- "Cellular organization and its use to control the function of cells and biotechnology." |
1993-1997 | Head, "Lab. of CNS Anesthetics" Institute of fine and organic chemistry. NAS RA |
2000-2006 | Head of the group of Biochemical Pharmacology, H. Buniatian Institute of Biochemistry, NAS RA. |
2006-2008 | Head, Lab. "Electrophysiological research methods" Scientific Res. Center of YSMI. |
2008 | Professor in biology (Diploma of the Higher Certificate Committee of Armenia P number 00539). |
Key research areas:
- Acad. LA Orbeli adaptive-trophic role of the cerebellum in conditions of hypothalamic- cerebellar regulation on the level of autonomous (sympathetic and parasympathetic) neck nerves.
- Inhibition in the cerebellar cortex
- Physiology of the cerebellum, brainstem motor nuclei, thalamus, basal ganglia, hippocampus, cortex and spinal cord.
- Plasticity of morphological and functional organization in norm and reorganization in the central nervous system in conditions of acute and chronic neurodegeneration of nonspecific-specific origin, including neoplastic degeneration and protection by biomodulators of different animal origin. The phenomenon of "sprouting" (axonal growths) to form a new functional synapses (plastic synaptogenesis) on the basis of differences in the characteristics of synaptic processes in such as axo-somatic and axo-dendritic that create the possibility of identifying new synapses formed as a result of the reorganization of the remaining links.
- The development of new experimental models and the procedure of identification of the collateral and terminal sprouting with formation of new synapses in subcortical and highly specialized cortical structures, the identification of direct mono-and polysynaptic distant manifestations of the reorganization of the projections (when replacement of crossed with non-crossed), including feedbacks providing and controlling the reliability of newly formed ones in mature animals on the model with uniform distribution of destructible and reorganized contacts.
- Effect of various biochemical compounds, in particular, various neurohormones (family of proline-rich peptides), animal venoms, proteoglycans of embryonic origin, and melanin on the electrical activity of single neurons of the brain and spinal cord (joint program with Inst. of Biochemistry, NAS RA; lab of pathologic anatomy; Depts of Biochemistry and plastic reconstructive microsurgery of YSMU).
- With Institute of Biotechnology, NAS of Armenia to initiate and accelerate the processes of plastic rehabilitation in conditions of the neurodegenerative changes of non-specific origin as a result of injury (lateral hemisection of the spinal cord, neurotomy), intoxication and on specific models of neurodegenerative diseases (Alzheimer's disease, Parkinson's disease) with the prospect of the use of these protectors in clinical practice.
- The activity of spinal cord neurons in the dynamics of acute and chronic hypocalcemia following paratireoidectomy and hypercalcemia and after the administration of parathyroid hormone, the effect of parathyroid hormone in a non-specific (traumatic) and specific (Alzheimer's and Parkinson's), neurodegeneration (in collaboration with the Dept of Normal physiology of Yerevan State Medical University) in combination with hormonal disturbances, particularly in conditions of ovariectomy and adrenalectomy.
- Neoplastic neurodegeneration associated with impaired blood circulation and on the model of malignant anemia, and protection of various biomodulators of the animal origin (ISTC program and Institute of Biochemistry, NAS of RA), as well as with the innervation of the bone marrow.
PERSONAL ADVANCES
It has been presented the confirmation of acad. L.A. Orbeli conception about adaptation-trophic role of cerebellum in condition the hypothalamo-cerebellar regulation on the level of autonomic (sympathetic and parasympathetic) cervical nerves, activated in beat with cardial and respiratory deviations. It has been revealed the changes of its activity under stimulation of sympathetic vasoconstrictive and vasodilatating hypothalamic centers and their bringing to initial level after stimulation of corresponding section of cerebellar cortex.
Firstly has been proved the presence of expressed inhibition in cerebellar cortex (by mean testing of a multitude analogues of GABA (α-, β-, δ-, θ-ABA ) on example of dendritic potentials up to opening by Eccles the inhibiting interneurons and counterbalance the presentations, in particular, Italian school of investigators (Provini L, Strata P.,1968) about scarcity of inhibition in this structure.
Over a period of many years, by technique of intracellular recording systematically studied the neural and synaptic organization of important links of CNS motor system in norm with revealing the multitude new connections. In particular, has been carried out systematic investigations of afferent and efferent connections and internal neuronal organization of red nucleus in narcotized and awake animals in acute and chronic experiments, allowing to reveal multitude new connections, the specifics of excitatory distribution in main trunk and collaterals of rubro-spinal neurons, projected to different nuclei of brainstem (for example, precerebellar sensory), the presenсe of interneuronal apparatus and others, that allow to revise conventional scheme of central organization of specialized movement control of Japanese and west scientists (in particular, Massion J., Sasaki K. 1979 and, Evarts E., Thach W., 1969), excluding the necessity of isolated presence of programmed and realizing execution systems, with advancement principally new model of central organization of precise movement control in norm. The mentioned advances formed the basis of candidate and doctoral dissertataions, as well as Monograph in co-authorship with аcad. Fanardjian in publishers «Nauka» in 1992. In 1984 under study of specificity of distribution of excitation in basic trunk and collaterals of motor neurons, has been discovered the mechanism of spreading of excitation in axonal system («efferent synthesis»), providing the execution of specialized movements. According to: the velocity of impulse conduction raises with increase distance between efferent neuron and neuron-target. In other words, independently of the site of collateral origin from parents' axon, their caliber and extension, time of arrival of impulses to different target practically identical. The given phenomenon underlying any precise movements, needing in simultaneous complex involving of different sites of motor system. For example, the essentials action, as taking object off a table, believe the simultaneous contraction of certain muscles of eyes, body, limbs, and relaxation of those antagonists.
Firstly functionally has been confirmed the presence of feedback in brain (on example of rubro-interposital projection), that will noted by leader of neuromorphology–Brodal A. on Nobel symposium in Sctocholm, then electrophysiologically revealed and described multitude feedbacks in important links of movement central organization systems of intact brain and its formation in pathology (see below).
It has been developed the conception of required presence of interneurons for acceptance the population of neurons as center that is approved on Moscow symposium “The integration of neurons in center”.
By being the scientific consultants of Institute of balneology and physiotherapy Ministry of Health of Armenia on the bases of studies, conducted on the numerous patients by deforming arthrosis of coxofemoral joint, has been presented two methodical recommendation (with А.А. Simonyan), approved in 1984 by direction of medical-prophylactic help of MH Armenia, in which firstly in arthrology has been suggested the use of "Н" – reflex diagnostic, prognostic and medical approach; moreover the possibility of reliable accounting at the same time objective functional state of neural-muscular apparatus of limbs allow bring in essential changes in generally accepted classification in orthopedics.
In 1993-1997 he pluralistically lead by laboratory of pharmacology the analgetic means of CNS Institute of fine organic chemistry NAS of Armenia in which under his immediate participation work out new and introduced contemporary methodical approach on indexation of analgetic means.
It has been studied the spare capacities of nervous system on model of local insults (partial differentiation) in important links of cortical-subcortical motor centers of brain. According to contemporary presentations, in the basis of the brain reorganization under pathology lies the plastic synaptogenesis, connected with unique “sprouting phenomenon”, leading to formation of the new pathways (collateral sprouting) and functioning synapses (terminal sprouting). The study of given phenomena became enable only due to acquirement by method of intracellular registration of synaptic processes and identification in different sites of neuron. The history of question has been connected with many years accumulation of experimental and clinical materials only with phenomenological point of view, without entry in mechanisms. And only in 60-th years of last Century the Japanese scientists under leadership of prof. N. Tsukahara firstly electrophysiologically proved the presence of “sprouting phenomenon” on the subcortical level on immature animals and proposed the universal model, which on the strength of conservatism, limited the subsequent development of study of this important phenomena in other sites of CNS. On the bases of proposed new models and methods of approach (electrophysiological and morphological in condition of cortical and subcortical injures) of revealing the ““sprouting” phenomenon in important links of central organization of movement on the level of both universal subcortical and high specialized cortical structures), carried in principal correctives in main postulates of Japanese scientists – founders of this important direction in contemporary neurophysiology:
- It has been shown the possibility of expressed neuronal reorganization on big extension in mature animals, unlike approved by Japanese scientists the possibility reorganization only in immature animals and on non great quantity of neurons-targets.
- Model of Japanese scientists foresee obligatory precise spatial demarcation of injured and reorganized synaptic inputs on soma-dendritic membrane on neurons with dislocation of contacts from dendrite on soma in result of release of vacancy on somatic level. On own model, we shows dislocation of contacts and backwards direction, from soma on dendrite. Moreover, on our new model without spatial demarcation of synaptic inputs in more specialized cortical structures has been shown dislocation, no determined by the presence of vacancy.
- Firstly under simultaneous intracellular registration from two neurons of cortex and thalamus, has been shown the formation of feedback, providing and controlling safety of new formed direct contacts, that is then was revealed practically in all links of movement system of brain in pathology.
- Japanese scientists affirmed the possibility of sprouting on level of CNS only in monosynaptic projection. We are has been proved the formation of “distant” polysynaptic sprouting, that is was noted prof. Ioffe as important discovery on All-USSR symposium in Vinnica.
- It has been revealed lesser degree of collateral sprouting evidence (i.e. the formation of new projection pathways) in hierarchically higher structures and more specialized owing to natural greater vulnerability, in other words, in pathology to its possible only terminal sprouting.
- The Japanese investigators approved plastic changes only in site, symmetric to injured site. It has been discovered the systemic sprouting in intact hemisphere, connected with reorganization not only in injured structure, but and functionally connected its structures. This evidently it is necessary for protection the temporal and hierarchic succession of the information arrival.
- Finally, firstly has been described the combined sprouting, expressed at involvement of structures, immediately no connected with injured.
- Moreover, has been shown extraordinary stability of all above described compensatory shifts under long-term (to 2-3 years) maturing of animals after insults.
Above mentioned additions to conception of Tsukahara’s school will accepted founders and testify, that even focal lesions of CNS accompanies the reorganization and systemic reply of brain in whole. The given advances summarized in monographs “Sprouting phenomenon and Brain Plasticity”, be found on stadium preparation for publication in publishers Elsevier. Given the high assessment of results, presented in monograph by well-known specialists of marked regions: above-mentioned Japanese scientists, American scientists from Columbian University prof. Dominick Purpura and head of Psychiatry and neurobiology department prof. Martin.