Reflection of the plastic properties of 2 neurons with a common monosynaptic input in the statistical characteristics of their impulse activity

Changes of cross-correlation histograms (CCH) of impulse trains and of mean interspike intervals (ISI) of neurones N1 and N2 with a common monosynaptic excitatory or inhibitory-excitatory input from N3, at changes of efficiency of interneuronal connections, neurone excitability and summate action on them of independent random afferent synaptic inflows were studied by methods of mathematical and biomathematical modelling of neuronal interaction. It was shown that the increase of amplitude of the central peak (trough) of a normalized CCH of N1-N2 accompanied by reduction of mean ISI of N1 and N2, is either a sign of an increase of the amplitude of postsynaptic potentials of N1 and N2 elicited by impulses of the nonrecorded N3 or a sign of an increase of mean ISI of N3.     

Reflection of the plastic properties of the simplest neuronal associations in statistical characteristics of the spike activity of their elements. Polysynaptically linked neurons

Changes of crosscorrelation histograms of trains of action potentials and mean interspike intervals of polysynaptically connected neurones were studied by means of mathematical modelling of synaptic neuronal interaction at changes of efficiency of interneuronal monosynaptic connections, at changes of neuronal excitability, and at changes of total action on them of independent disorderly afferent synaptic inflows. Increase of amplitude of the main maximum (minimum) of the normalized crosscorrelation histogram of trains of action potentials accompanied by reduction of mean interspike intervals of both neurones, was shown to be a unsignificant indication of an increase of efficiency of polysynaptic excitatory (inhibitory) connections between the neurones (due to modification of synapses or to a change of the functional state of interneurones).     

Reflection of the plastic properties of monosynaptically interconnected neurons in the statistical characteristics of their spike activity

By mathematical and biomathematical methods of neuronal interaction modelling, changes were studied of cross-correlation histograms (CCH) of impulse flows and of average interimpulse intervals of monosynaptically interconnected neurones, at changes of efficiency of forward and backward connections, of excitability of neurones and of summate action on them of independent random afferent synaptic inflows. It is shown, that a single sign of efficiency increase of monosynaptic excitatory or inhibitory connection between neurones (amplitude increase of the corresponding postsynaptic potential) consists in amplitude increase of the main peak or trough the rated CCH of their impulse flows, followed by a decrease of average interspike intervals of both neurones.     

The analysis of the impulse activity of 2 neurons monosynaptically excitable by a 3rd using cross-correlation histograms and Cox's method. The potential for detecting neuronal and synaptic plasticity

By a method of mathematical modelling exogenic stationary random single impulse activity was reproduced of two neurones (N1 and N2), monosynaptically excited by a third one (N3). Value P12, defined from cross-correlation histogram and Cox coefficient beta 12 were used to evaluate the degree of dependence of N1 and N2 impulse trains. Dynamics of P12, beta 12 and of values of P1*, P2* and P3* proportional to corresponding mean interimpulse intervals of N1, N2 and N3, was studied under changes of efficiency of interneuronal connections, neurones excitability and summate action on them of independent random afferent synaptic inflows. It has been shown that the increase (decrease) of P12 or beta 12 accompanied by decrease (increase) of P1* and P2* is a sign of plastic change or N3 discharges frequency, or a sign of plastic changes of the amplitude of excited postsynaptic potentials elicited by these discharges.     

Temporal organization of interneuronal relations in the cerebral cortex of the cat in relation to the level of alimentary motivation

By means of records of multicellular activity, interneuronal relations and their modifications in two cortical zones (Visual and motor) were studied in cats at different levels of alimentary motivation. For quantitative evaluation of interneuronal relations the statistic method of cross-correlation analysis of impulse trains was used in determining the probability of the appearance of the discharge of one neurone after the impulse of the other one. For groups of neurones in both investigated cortical areas, three-neurones microsystems were singled out and their activity was analyzed by temporal parameters of interaction between neurones at the interval of 120 ms, both within one microarea (intraanalyzer connections) and between microareas of two cortical zones. The correlation of temporal parameters of interneuronal connections (temporal delays in the activity of neuronal pairs) changed depending on spatial localization of neurones and functional condition of the animals. The existence is suggested of "informational" (1-30 ms) and "motivational" (90-120 ms) values of interneuronal relations for interanalyser connections.     

Shape of the auto- and cross-correlation histograms of the spike trains of 2 neurons with a common monosynaptic input

Form of auto- and cross-correlation histograms of impulse trains of two neurones with a common monosynaptic input from the third one were studied by methods of modelling of neuronal interaction--biomathematical (computer controlled experiment on molluscs neurones) and mathematical--in wide physiological ranges of values of parameters characterizing properties and conditions of functioning of neurones and synapses. In conditions typical of the central nervous system of mammals (but not invertebrates), when neurones are subjected to intensive random afferent synaptic bombardment and reveal no pace-maker properties, each of the possible type of common monosynaptic inputs to two neurones--excitatory, inhibitory or inhibitory-excitatory--is manifestated in cross-correlation histogram of their impulse trains in a specific way.     

Types of correlative relations of the neuronal impulses of the visual and sensomotor areas of the neocortex in the rabbit

Neuronal activity of the visual and sensorimotor cortical areas was simultaneously recorded in intersignal intervals in rabbits with conditioned reflexes to light and sound. ES-1020 computer built cross-correlation (CCH) and autocorrelation (ACH) histograms of impulse activity of the se neurones. Analysis of CCH form, built with a bin of 2 ms gave no convincing proofs of the presence of synaptic connections between neurone of the visual and sensorimotor cortical areas and of influences from a common source with few switchings on interneurones. Analysis of CCH built with bins of 10 and 30 ms, allowed to single out primary and secondary peaks and troughs. Wide primary peaks with the base covering the beginning of the coordinates, were met in 51.9% of cases; wide peaks, greatly shifted relatively to the coordinates beginning,--in 40.9% and trough--in 7.2% of cases. Secondary peaks did not always reproduce the ACH form of impulses trains of recorded neurones. The CCH analysis allowed to suggest two basic mechanisms, eliciting the correlated discharges--action of common input and influence of the neurones of one area on the other through a number of interneurones. It was not always possible to separate these two cases by means of CCH. In a number of cases, a more complicated character of neurones interaction could be suggested.     

Possibilities of detecting the plasticity of monosynaptic excitable connections during the analysis of impulse activity of neurons using cross-correlation histograms and Cox's method

By the method of mathematical modelling, stationary irregular exogenous impulse activity of two monosynaptically connected neurones (N1 and N2; excitatory connection) was reproduced. The degree of impulse flows N1 and N2 dependence was estimated by the value P12, proportional to the height of crosscorrelation histogram peak, and by Cox's coefficient beta 12. The dynamics was studied of P12, beta 12 and of values P1* and P2*, proportional to mean interpulse intervals of N1 and N2, at changes of connection efficiency, neurones excitability and of influence of afferent synaptic bombardment on them. The following signs of modification of existing between N1 and N2 monosynaptic excitatory connection were established: 1) change of P12 in direction opposite to that of P1* and P2* change; 2) differently directed changes of beta 12 and P2* of postsynaptic N2.     

Contour of auto- and cross-correlation histograms of the spike flows of monosynaptically connected neurons

By methods of neuronal interaction modelling--biomathematical (computer controlled experiment on molluscs neurones) and mathematical--in wide physiological ranges of parameters values, characterizing properties and conditions of neurones and synapses functioning, the forms were studied of auto- and cross-correlation histograms of impulse flows of neurones at forward and backward monosynaptic connections between them. Specific form is established of cross-correlation histogram of impulse flows of interconnected neurones in conditions typical of CNS of mammals, when the neurones are subjected to intensive random afferent synaptic bombardment and do not reveal any pace-maker properties. It is also shown that random afferent synaptic bombardment prevents the appearance of excitation reverberation in closed neuronal circuits.     

Comparative study of interneuronal relations in the auditory cortex of awake and anesthetized cats

The character of interneuronal relations in the auditory cortex of alert and anaesthetized cats (nembutal) with chronicly inplanted electrodes was studied with the method of statistic analysis of cross-intervals of the two impulse series. The analysis of the histograms, obtained by means of processing a neuronal activity, showed that nembutal did not eliminate the dependent relations between neurones and that in the majority of cases the types of these relations are either retained or supplemented with new components. Experiments with a reduced dose of nembutal permitted to trace in time the changes in the amount of the inhibitory and excitatory interrelations in the anaesthetized state, and to compare these changes to the changes in the frequency of spike activity. It was found that nembutal predominantly suppresses the activity of the neurones, generating small spikes. The number of inhibitory connections is reduced simultaneously. Such synchroneity permits to assume the participation of the neurones generating small spikes in the establishment of inhibitory interrelations in the cat auditory cortex.     

Changes in pyramidal tract response to direct stimulation of the sensomotor cortex of the rabbit during formation of a conditioned reflex

Changes of pyramidal tract (PT) response were analyzed, reflecting the final result of cortical interaction in the process of combinations of direct stimulations of cortical surface in nonimmobilized and unanaesthetized rabbits. It has been shown that in a situation, modelling conditioning, changes take place of the first direct component--the D-component--of the PT response (reflecting the excitability of the PT neurones), as well as changes of the successive indirect synaptic component--I-component (reflecting the excitability of presynaptic cortical elements and of intracortical synaptic connections). I-component changes were significantly more expressed. In most cases the I-component of the response was increased. The obtained data testify to an increase of synaptic efficiency in the process of temporary connection formation and to possible change (increase or reduction) of excitability of PT neurones.     

Temporal structure of the spike trains of neuronal pairs in the neocortex during calm wakefulness in rabbits

For revealing the conjugation of impulse activity of simultaneously recorded neurones in the visual and sensorimotor areas of rabbits neocortex, histograms were built of cross- and autocorrelation (CCH and ACH) of their discharges sequences. From successions of discharges of the visual cortex neurones, forming pairs of cells acting in correlation, spikes were singled out conjugated with neuronal discharges in the sensorimotor area, and their ACHs were built. In 77% of cases a resemblance was observed of temporal structure of conjugated discharges and real spike sequences, in 23%--there was no such resemblance. Analysis of conjugated discharges ACHs showed that they appeared predominantly periodically (87% of cases). The number of fragments with periodic discharges frequency within delta-frequency range from 3 to 4 Hz prevailed.     

The monosynaptic connection between identified neurons in the snail

Monosynaptic connection between two identified neurones was investigated using electrophysiological and morphological methods in preparation of isolated nervous system of the snail Achatina fulica. Intracellular pressure injection of cobalt chloride was used for staining of neuronal branches. Electrophysiologically revealed synaptic connection between two giant neurones was identified to be monosynaptic by morphological methods.     

Functional organization of local neuronal networks in the cat neocortex. Dependence on the food motivation

The multiple unit activity (MUA) from clusters of adjacent neurones in deep layers of the frontal and motor cortex was recorded in alert cats with different levels of alimentary motivation. Up to 7 spike trains were selected from the MUA. Neurones in the local circuits could be divided into 2 groups: large neurones with prevailing divergent characteristics, and small neurones with prevailing convergent characteristics. A 24-hour food deprivation altered the cross-correlation interneuronal connections with a time delay within the range of 2 to 100 ms.     

Dependence of Transformation of Intrinsic Rhythmic Impulse Activity of Neurons on Spatio-Temporal Organization of Synaptic Actions on Dendrites: A Simulation Study

The aim of the study to elucidate the biophysical mechanisms able to determine specific transformations of the patterns of output signals of neurons (neuronal impulse codes) depending on the spatio-temporal organization of synaptic actions coming to the dendrites. We studied mathematical models of the neocortical layer 5 pyramidal neurons built according to the results of computer reconstruction of their dendritic arborizations and experimental data on the voltage-dependent conductivities of their dendritic membrane. This work is a continuation of our previous studies that showed the existence of certain relations between the complexity of neural impulse codes, on the one hand, and the complexity, size, metrical asymmetry of branching, and nonlinear membrane properties of the dendrites, on the other hand. This relation determines synchronous (with some phase shifts) or asynchronous transitions of asymmetrical dendritic subtrees between high and low depolarization states during the generation of output impulse patterns in response to distributed tonic activation of dendritic inputs. In this work we demonstrate the first time that the appearance and pattern of transformations of complex periodical impulse trains at the neuron’s output associated with receiving a short series of presynaptic action potentials are determined not only by the time of arrival of such a series, but also by their spatial addressing to asymmetric dendritic subtrees; the latter, in this case, may be in the same (synchronous transitions) or different (asynchronous transitions) electrical states. Biophysically, this phenomenon is based on a significant excess of the driving potential for a synaptic excitatory current in low-depolarization regions, as compared with that in high-depolarization dendritic regions receiving phasic synaptic stimuli. These findings open a novel aspect of the functioning of neurons and neuronal networks.     

AN ELECTRON MICROSCOPIC STUDY OF THE DEVELOPMENT OF SYNAPSES IN CULTURED FETAL MOUSE CEREBRUM CONTINUOUSLY EXPOSED TO XYLOCAINE

Explants of fetal mouse cerebral cortex, continuously exposed to the local anesthetic Xylocaine from the time of explantation to the time of fixation, were examined in the electron microscope to determine whether morphologically normal synapses and potentially functional interneuronal synaptic networks can form in the absence of electrical impulse activity. Morphological differentiation of complex synaptic networks proceeds normally, and the drug does not alter the fine structure of the formed synapses. These observations are consonant with the electrophysiological data which show that the potential for complex bioelectric activity can develop in the absence of its expression. The development and maturation of functional synaptic networks, then, is not contingent upon prior electrical impulse activity. These data support the concept that organized neuronal assemblies are formed in forward reference to their ultimate function.     

Effect of disulfiram on the interconnected activity of cortical neurons in trained cats

The action of disulfiram on interconnected activity of neurones in the visual and motor cortical areas was studied in cats with food-procuring conditioned responses to light. Multiunit activity was recorded from the areas and, by means of amplitude discrimination, separated into impulse flows. Crosscorrelation analysis of the impulse series was used to reveal the character and temporal parameters of interconnected activities of neurones firing in correlation within the limits both of the same cortical area and of the two different ones. A depressing action was shown of the disulfiram on the food-procuring reaction, accompanied by a decrease of the number of pairs of neurones from the visual and motor cortical areas mostly acting in interconnection, interactions with long time delays being mostly affected. The character of action of neighbouring neurones in the visual and motor cortical areas changed in the same direction, expressed in their firing by a "common source" type. The question is discussed of disulfiram influence on interneuronal connections of both types suggesting a decrease of alimentary motivation as well as disturbance of food-procuring conditioned motor coordination.     

Effect of serotonin on the activity of the neurons involved in the realization of the avoidance reflex of the snail

Bath application of 10(-5) mol/l of serotonin (5-HT) elicited a 50% increase of summary EPSPs recorded in command neurones for avoidance behaviour. No significant changes of rest potential and input resistance were seen in these cells. 5-HT evoked an increase of spontaneous level of firing in motoneurones involved in the same reflex, as well as an increase in the number of spikes which paralleled increase of EPSPs to the same stimulus in command neurones. In sensory cells, presynaptic to the command neurones, application of 5-HT evoked a significant increase of excitability and of input resistance. Monosynaptic EPSPs recorded in the command neurones showed a 40% increase after serotonin application. It is concluded that the major locus of plastic changes evoked by 5-HT application in the neuronal chain underlying avoidance reflex is the synaptic contact between sensory and command neurones.     

Developmental changes in transmitter sensitivity and synaptic transmission in embryonic chicken sympathetic neurons innervated in vitro.

Dispersed neurons from embryonic chicken sympathetic ganglia were innervated in vitro by explants of spinal cord containing the autonomic preganglionic nucleus or somatic motor nucleus. The maturation of postsynaptic acetylcholine (ACh) sensitivity and synaptic activity was evaluated from ACh and synaptically evoked currents in voltage-clamped neurons at several stages of innervation. All innervated cells are more sensitive to ACh than uninnervated neurons regardless of the source of cholinergic input. Similarly, medium conditioned by either dorsal or ventral explants mimics innervation by enhancing neuronal ACh sensitivity. This increase is due to changes in the rate of appearance of ACh receptors on the cell surface. There are also several changes in the nature of synaptic transmission with development in vitro, including an increased frequency of synaptic events and the appearance of larger amplitude synaptic currents. In addition, the mean amplitude of the unit synaptic current mode increases, as predicted from the observed changes in postsynaptic sensitivity. Although spontaneous synaptic current amplitude histograms with multimodal distributions are seen at all stages of development, histograms from early synapses are typically unimodal. Changes in the synaptic currents and ACh sensitivity between 1 and 4 days of innervation were paralleled by an increase in the number of synaptic events that evoked suprathreshold activity in the postsynaptic neurons. The early pre- and postsynaptic differentiation described here for interneuronal synapses formed in vitro may be responsible for increased efficacy of synaptic transmission during development in vivo.