SYSTEMOGENY

1. SYSTEMOGENY

2. Function: Traditional and Systemic views Instead of regarding, e.g., “vision”, “audition”, “attention”, “motor control” and “motivation” as functions, a fundamentally different definition of a “function” was elaborated in functional system theory. In this theory, function refers to an achievement of a result through the realization of a certain functional system. Such a function cannot be attributed not only to certain neural networks but even to the brain. It relates to the whole organism.

3. Systemogenesis versus Organogenesis

4. Systemogeney and Ontogeny During early ontogeny, those differently localized elements undergo selective and accelerated maturation that is essential for achieving the results of the systems, providing for the survival of an organism at the early stages of individual development.

5. Systemogeny takes place not only during the early ontogenetic period, but also during adult development • The formation of a new behavioural act is always a formation of a new system

6. The essence of the basic idea underlying the absolute majority of studies within the framework of the ABC paradigm

7. Long-Term Potentiation and Evoked Spike Responsesin the Cingulate Cortex of Freely Mobile RatsA. G. Gorkin, K. G. Reymann,and Yu. I. AleksandrovNeuroscience and Behavioral Physiology, Vol. 33, No. 8, 2003 Long-term potentiation of EP in the cingulate cortex after tetanic stimulation of the subiculo-cingulate tract. The ordinate shows the EP rise rate, % of initial, and the abscissa shows time, h. The time during which post-tetanic EP was significantly (t test, p < 0.05) different from initial is noted by the line and asterisks.

8. Re-juvenilization Nowadays it is commonly accepted that many regularities of modification of functional and morphologic characteristics of neurones, as well as of control of gene expression, serve as a basis for the formation of adaptive behaviour in adults, and are comparable to those found at the early ontogenetic stages.

9. Early genesLate genesMorphologicalmodifications

10. ·Neuronal death that follows seizures, cerebral ischemia, etc is initiated by overactivation of glutamate receptors, and an increased intracellular concentration of Ca2+. Increased concentration of Ca2+ causes transcriptional activiation of so-called “cell-death genes”. Immediate-early genes play a central role in converting extracellular signals into long-lasting alterations in cellular phenotype. ·The existing data provide strong evidence for a relationship between PERSISTENTactivation of immediate-early genes and delayed neuronal death (that is a form of programmed cell death, or apopotosis). A similar relationship between persistent expression of c-fos, and cell deathin neural and non-neural systems was apparent. ·By contrast, TRANSIENTinduction of immediate-early genes seems to occur in neuronal populations that are destined to survive. SS. Schreiber & M. Baudry Trends Neurosci., 1995, 18, 446.

11. It can be suggested that the expression of c-Fos is a prerequisite that allows other transcription components carry out their specific decision for death or survival. (p.2736) Lee Y., Park K.H., Baik S.H., Cha Ch.I. Attenuation of c-Fos basal expression in the cerebral cortex of aged rat. NeuroReport, 1998, 9, 2733-2736

12. Compensation Primary and/or Secondary assortment? ? Pathological state ? ? consolidation LG To learn? EG Secondary assortment Systemogenesis Systemic specialization or Neuron mismatch NEONEUROGENESIS EG EG Normal state Learning ? To die? death DG Adults Early onotogeny Maturation Primary assortment Systemic pre-specialization

13. Neuron is always active Each step in neuronal elimination is active. Neurons of different classes express receptors whose activation can lead to their death. C. Raoul, Pettmann B. & Henderson C.E. Active killing of neurons during development and following stress. Current Opin. In Neurobiol. 2000, 10, 111-117

14. Four deaths and a funeral: from caspases to alternative mechanisms. Nature Reviews, 2001, 2, 1-10 Leist M. & Jaattela M. Cell suicide in the adult nervous system has serious implications for the whole organism Altruism and Suicide

15. Selection instead of Instruction • Both in biology and in cognitive sciences there is a principled discontinuation of the search for a meager stock of all-purpose innate “primitives”, out of which everything else ought to be “constructed” through a process of “enrichment”, mediated by “association” … • The present trend is to grant a very rich innate repertoire and then look for the mechanisms of internal selection. • The key role of the environment is not that of supplying more structure, but rather that of steering a selection. • We should conceive of “learning” as a process of triggering, filtering, parameter-setting, progressive specialization and selection. A SELECTIVE THEORY IS BY NOW ALWAYS THE MOST PLAUSIBLE CANDIDATE FOR EVERY PROCESS OF ACQUISITION [Piattelli-Palmarini M. Evolution, selection and cognition: From “learning” to parameter setting in biology and in the study of language. Cognition, 1989, 31, 1-44]

16. The system-selective concept of learning

18. “Place-cells” in rats

19. “Face neurons”in monkeys

20. “Face neurons”in human beings

21. «Gnosticneurons» by Konorsky

23. New Neurons Studies of information storage in model neural networks have shown that adding new learning sequentially to the network can result in "catastrophic interference" [McCloskey M. & Cohen N.J., 1989]. New information can obscure previously stored information. If new memories got new neurons with new connections, catastrophic interference might be avoided. (W.T.Greenough et al., Nature Neurosci., 1999)

25. Immune Cells Never Forget Once learned, some abilities, such as swimming or riding a bike, are never forgotten even after years without practice. Others, say running a marathon, need a regular brushing up. Immunologists have long debated which category our immunological memory falls into. Once immune cells learn to recognize a particular antigen, such as a viral protein, do they need constant reminders to stay on top of things, or are their memories permanent? Two reports in this week's issue of Science … now bolster the notion that immune cells never forget. … Most experts are convinced that memory T cells don't need constant stimulation … to stay in shape Michael Hagmann Science vol. 286, # 5444, 1999: 1266 - 1267

26. Konorski’s Concept of Gnostic Areas and Units • Unitary perceptions are mediated by the discharge of single neurons, called gnostic units. • Gnoctic areas are considered as files of gnostic units representing all the unitary perceptions established in a given subject. • Once a potential gnostic unit had been preemted by a particular stimulus pattern so as to become transformed into an actual gnostic unit representing that unitary perception, it become resistantto any new stimulus pattern. [Konorski J. Integrative activity of the brain. An interdisciplinary approach. Univ. Chicago Press: Chicago, 1967, 531 p.]

27. Intensity of c-Fos expression is the highest in the retrosplenial cortex which has a higher number of specific behaviorally specialized neurons

28. bar-pressing related neurons 100 m 100 m 0.23% 0.04% 23.6% 3.6% RELATIOSHIPS BETWEEN c-FOS EXPRESSION AND BEHAVIORAL SPECIALIZATION OF NEURONS Retrosplenial cortex Motor cortex 1.11% 0.98% out of Fos-positive

29. NeoNeurogenesis • Newly generated neurons in the adult are not only affected by the formation of a hippocamapl-dependent memory, but also participate in it. • The new cells are about 1-2 weeks of age when they become involved in the learned response. • This ability to undergo rapid structural change may be a characteristic of immature neurons that makes them ideally suited for forming associations between stimuli. • Newly generated neurons may not be used for learning under more lenient conditions, but become involved as task demands increase. [T.J. Shors, G. Miesegaes, A. Beylin, M. Zhao, T. Rydel, and Gould E. Neurogenesis in the adult is involved in the formation of trace memories. Nature, 2001, 410, 372-375]

31. The new system is added to the existing systems; newly formed systems do not substitute for previously existing systems, but are "superimposed" over them.

32. What does it mean - "to superimpose, but not to substitute"? Many experiments have demonstrated that a complex instrumental behaviour is mastered not only through the realization of new systems, that were formed during the process of learning the acts comprising the behaviour, but also by the simultaneous realization of older systems, that had been formed at previous stages of individual development.

34. 5 0 1.0 1.0 Behavioral Act 1 .8 .8 .6 .6 .4 .4 .2 .2 5 7 4 5 7 1 2 3 4 6 8 9 10 1 2 3 6 8 9 10 1 sec Behavioral Act 2 NEW SYSTEMS Individual development OLD SYSTEMS

35. Behavioral Act 1 Behavioral Act 2 SYSTEMS NEW Individual development SYSTEMS OLD

36. Behavioral Act 1 Behavioral Act 2 SYSTEMS NEW Individual development SYSTEMS OLD 500 msec

37. Example of the activity of the M-neuron that was activated during rightward body movement. Activations of this neuron appear during the turning to the right when approaching the pedal on one side of the cage (FC), side of the cage (RC) or during this movement in defensive behavior (DB).

38. The realization of behaviour is the realization of the history of behavioural development, that is, of many systems, each fixing a certain stage of development of the given behaviour.

39. Behavior is a simultaneous realization of a set of systems ranging from the most archaic to the newest ones Hippocampus Position EMG Actogr. front Actogr. rear Behavioral Act 1 Behavioral Act 2 Neuron SYSTEMS NEW Motor cortex Neuron Individual development Actogr. front SYSTEMS OLD Actogr. rear Neuron Actogr. front Actogr. rear from a hand from the floor mesencephalic nucleus Trigeminal Neuron Jaw mov. EMG 500 msec

40. Memory Environmental Parameters afferentation of the result Acceptor of action’s Decision Triggering Result result of the action making stimulus Program of the action Environmental Action afferentation Motivation Afferent synthesis R R r r r r r r r r n n + 1 1 2 1 2 3 1 2 3 Act n T Act n+1 T Act n+2

41. RE -CONSOLIDATION - the modifications of pre-existing memory

42. Definitive behavior mismatch Actualization MEMORY Re-consolidation in consequence of memory reactivation

43. LEARNINGTWO CLOSELY CONNECTED PROCESSES: • SPECIALIZATION - therecruitment of new neurones into the subserving of specific new behaviours • ACCOMMODATIVE RE -CONSOLIDATION - the modifications of pre-existing behaviours neurones

44. Memory “projection” to cerebral structures Our recordings of unit activity in many cerebral structures during instrumental behavior have demonstrated that neurons with new specializations are abundant in cerebral cortex, whereas phylogenetically archaic and peripheral structures contain very few of them.

45. The specificity of memory “projection” to cerebral structures is determined by the characteristics of neurons composing these structures. These characteristics determine the involvement of neurons of the given structure into the formation of the certain behavior.

46. Brain Research 876 (2000) 154–165Effects of ethanol on hippocampal place-cell and interneuron activity* Aaron M. White , Phillip J. Best

48. Definitive behavior Mismatch Actualization MEMORY Re-consolidation in consequence of memory reactivation

49. At the beginning of learning 1-EGE EGE EGE Pre-exiting memory Mismatch

50. 2-Tets Mismatch Pre-exiting memory