LABORATORY OF GENETICS OF THE HIGHER NERVOUS ACTIVITY

(Head Ц A. I. Vaido)

In 1933, by I. P. Pavlov's proposal, studies on experimental genetics of the higher nervous activity started in Koltushi, on the base of the Biological Station. The founded laboratory was headed until 1949 by Prof. E. A. Ganike, since the mid-1950s, Prof. V. K. Krasussky, since 1962, Prof. V. K. Fedorov, since 1972, Prof. N. G. Lopatina. From 2000, the head of the Laboratory is Biological Sciences Doctor A. I. Vaido.

Dr.. A.I.Vaido and co-workersDuring the entire history of this Laboratory, its main research problem has remained the same: investigation of the genetical basis of behavior. A careful genetic analysis was consecutively performed of the capability for learning, the main properties of nervous processes, functional state of the nervous system. In compliance with world trends of development of behavioral genetics and neurogenetics there was performed a transition from evaluation of contribution of genotype and environment to processes of the higher nervous activity to study of specific pathways of their effects on functioning of the nervous system and behavior.

Recently, investigations at the Laboratory are carried out along two directions: (1) the genetically determined tone of the central nervous system and mechanisms of the epigenetic (environmental, leading to a change of the genome functioning) control of adaptive behavior of rats selective in the Laboratory for excitability of the nervous system; (2) role of glutamate receptors and their interaction with kinurenins in realization of plastic processes in normal honeybees and in the bees mutant for genes controlling the kinurenin pathway of tryptophan metabolism роль. Based on results obtained on lines of rats, a hypothesis has been formed on specific mechanisms of the epigenetic control of brain functioning and adaptive behavior in connection with the genetically determined level of excitability of the nervous system. The experimental elaboration of this hypothesis has demonstrated both the pre- and the postnatal stress to lead to long-term differentiated changes of the number of neurons depending on genetically determined excitability of the nervous system and to modifications of the C-heterochromatin structural-spatial characteristics changing expression both of eu- and heterochromatin proteins.

For the first time, when using the current method of genetical knockout (antisense oligonucleotides), evaluation of the conditional reflex activity, and pharmacological analysis on honeybees there was revealed participation of central ionotropic (of NMDA- and non-NMDA-subtypes) and metabotropic glutamate receptors in formation of the post-tetanic potentiation phenomenon and in associative learning in insect as well as necessity of coactivation of the glutamate receptor subtypes in the process of formation of memory traces. Comparative analysis of pharmacological characteristics of ionotropic and metabotropic glutamate receptors in honeybees with normal level of kinurenins and with mutants experiencing their deficit also revealed for the first time a selective 1-2 order increase of sensitivity of the NMDA-, kainate, metabotropic glutamate receptors of the first class; this fact allowed proposing a hypothesis of effect of kinurenins on mechanisms of integration of glutamate receptors in postsynaptic membrane structures.

The obtained data not only are of the general theoretical significance, but also promote deciphering of etiopathogenetic mechanisms of a number of psychic and neurological human diseases (schizophrenia, syndrome of post-traumatic stress disturbance, tryptophanuria, epilepsy, Huntington's chorea, etc.). The Laboratory associated the close perspectives with detailed deciphering of mechanisms of morphological changes of brain structures and epigenetic modifications of neuronal genome in rats under conditions modeling the appearance of the human post-traumatic stress disturbance with subsequent correction of the appearing disturbances by methods of cellular therapy and gene engineering. Alongside this, studies will continue of the role of individual subunits of glutamate receptors in establishment of plastic processes in the honeybee nervous system with the use of various schemes of the functional gene knockout.
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