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Journal of Integrative Neuroscience, Vol. 8, No. 4 (2009) 453–469c
Imperial College PressDOI:10.1142/S0219635209002319
Research ReportPRINCIPLES OF CELLULAR-MOLECULARMECHANISMS UNDERLYING NEURON FUNCTIONS
ALEXANDER S. RATUSHNYAK
and TATIANA A. ZAPARA
Design Technological Institute of Digital Techniques SB RAS Novosibirsk, 63009, Russia 
ratush@mail.ru 
Received 27 October 2009Revised 2 December 2009In the present work, it was experimentally shown that a neuron
in vitro
was capableof responding in a manner similar to habituation, Pavlov’s reflex and avoidance of thereinforcements. The locality of plastic property modifications and molecular morphology,as well as the connection between functional activity and cytoskeleton have been revealed.A hypothesis is formulated that the neuron is a molecular system which may exercisethe control, forecast, recognition, and classification. The basic principles of the molecularmechanisms of the responses underlying integrative activity, learning and memory at theneuronal level are discussed.
Keywords 
: Neuron information functions; recognition; classification; forecasting; learning.
1. Introduction
For the past ten years, vast amount of experimental data have been accumulatedin neurobiological and cell molecular studies. The list of pathways of signal trans-duction of molecules, enzymes and genes taking part in the information processesis enormous. It allows understanding of the main principles of the organization andfunction of molecular information devices the neurons. However, unequivocalanswers to the main conceptual questions of bioinformatics have remained elusivestill. There is an opinion that such “analytic approach has been exhausted, we haveanother and possibly more difficult problem. We literally sink in data. You canconnect all data in the world, but without the model these data will always beinsufficient” [23].The main part of current neurobiological investigations is devoted to analysisof the processes taking place in synapses during learning and memorization andexecuted with the use of reduced neuronal systems as models, including those of mollusks [1,2,5,8,10,15,16,18,22,33]. Plasticity is a fundamental property of the nervous systems. One of the best characterized forms of synaptic plasticityis long-term potentiation (LTP) [7]. Currently, 1124 proteins have been identified
453
 
454
Ratushnyak & Zapara 
in the synaptic terminal and only 466 of them were validated by detection in twoor more studies [9]. DNA microarray techniques allowed examination of the char-acteristics of the activity-regulated genes (ARG) which alter their expression dur-ing tetanus-induced LTP. The ARG-associated processes are complicated, includingsignal transduction, transcription regulation, and modulation of synaptic structureand functions. Structural changes at the synapse and new synapse formation arethought to be critical for longer lasting LTP [25,32]. A significant number of ARGs are involved in neurite outgrowth and synapse formation. Many ARGs are impli-cated in the cytoskeleton regulation and cell-to-cell or cell-to-extracellular matrixinteractions. Activity-regulated expression of these genes may directly contributeto the synaptic modification or formation of the synapse, because some ARG pro-teins which regulate cell–cell/extracellular matrix interactions and cytoskeletons areknown to be enriched at the synaptic regions [27]. ARGs also reveal the novel molecu-lar processes underlying LTP. For example, CDC25B is an ARG that is a well-knowncell cycle regulator [13] but it plays a role in the regulation of synaptic plasticity aswell [27].Unlike an analytical path there is a direction in which the study of a cell andthe brain as a whole is directed first of all to creation of imitation models with theirsubsequent experimental verification mainly under the black box scheme. In thiscase, for the most part the verifications are restrained by creation of mathematicalmodels of different complexity levels. Until recently, a neuron was thought as aconductor of information and a simple threshold linear adder. Such ideas were usedas the basis for most of the neurocomputer metaphors. An attempt to bring theneuron model nearer to the real object was undertaken in the Blue Brain project[23]. The notion of neuronal cells as rather complicated molecular device is thebase of this project [14,17,20]. However, in this case undertaken attempts are also reduced to creation of a cell model based not on conceptual principles but onrather conflicting and inexhaustible experimental data. The results of such attemptsclearly demonstrate the problem of knowledge synthesis from the infinite body of information while the conceptual model is absent. The big set of neurobiologicalinvestigations of neurons were undertaken in the Blue Brain project to increase thedata volume, specify the data and take away the contradictions of known data. Thesestudies mainly touched on the function of ion channels and membrane mechanisms.Using these data and supercomputer IBM, a model of neocortical columns containingseveral tens of thousands of model neurons has been created. According to theauthor’s opinion, the model under development is similar to the rat brain neuronsand is exhausted by the limiting/existing possibilities of computer systems. However,it is not clear how fully this model reflects the real possibilities of simulated structure,because the function of this structure of the brain is still not fully revealed. Thusdistinction of power consumption and speed on several orders from prototypes canserve by the indirect evidence of considerable mismatches (not only “technological”ones). Unfortunately the real informational neuron properties were not the focus of study in this mega project. Works which showed that the simple neuronal structuresand separate cells are capable, in the experimental conditions, to generate enough
 
Principles of Cellular-Molecular Mechanisms in Neuron Functions 
455
complicated responses were not practically considered [3,8,11,16,22,24,34]. It is necessary to note that the data could not be used because of their incompletenessand inconsistency.The integration of the many known facts and the experimental results obtainedin the past years allow us to suggest that the neuronal cell has rather complicatedfunctions. However, on the conceptual level, the questions of the main informationalneuron properties are not been yet solved. There are no answers to the most concep-tually important questions. Namely, what is a neuron? Are its functions limited inthe nervous system by the simple operations of signal processing and signaling? Isit possible to selectively change the effectiveness of separate input of a neuron? Is itpossible to receive specific neuronal response after signaling from receptors to effec-tors by the non-selective intracellular pathways? Without solving these questions,the creation of models for both single cell system and higher level systems will onlylead to creation of simulations weakly resembling real neuronal systems.Solving these problems would permit development of the conceptual models of biological information systems. That in turn will bring closer possibility purpose-fully to solve problems of medical correction pathological and cognitive changes inthe nervous systems, and with another to use principles (and also molecular mecha-nisms) functioning of such biological prototypes of information systems in the fieldof neurocomputers nano- and molecular electronics.
2. Methods and Experimental Model
In this study, we attempt to solve the above questions. It is necessary to carryout direct investigations of isolated neurons with the aim to show the functionaland information possibilities of such cells. It was necessary to detect experimentallya change of the weights for separate inputs and fixation of new functional mean-ings by recording of spatial distribution of neuron activity. It is important on thereduced system (the isolated neurons) to determine experimentally the properties of processes of the functional plasticity and the participation of separate intracellularsystems in such processes.To achieve these tasks, the selection of the experimental model is important.The subject must be rather simple, but it must permit organization of several infor-mation inputs to control and modify the molecular organization. The methodolog-ical possibility of storage of the main properties is necessary. One of the subjectswhich fits the majority of these requirements is isolated mollusk’s neurons culti-vated outside of the organism. The large size of such cells permits organization of rather simple system of informational inputs. The present work was carried outusing this model. The functional activity of isolated cultivated mollusk’s neuronswas recorded using the imaging, microelectrode and patch-clamp techniques. Sev-eral types of the plasticity paradigms to be described below were developed. Theformation of external electric inputs and registration of ion channel functioning(molecules forming the output signal) on the micro-areas was performed using theglass coaxial micropipettes with 5
µ
m end diameter. Supplying the substances was

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