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.     

Characteristics of the systemic organization of the cortical neurons in various forms of the manifestation of the conditioned reflex to time

Conditioned food-procuring reflex to time (2 minutes interval) was elaborated in cats. By the method of cross-correlative analysis the combined neurones activity in microareas and between microareas of the motor cortex was compared at various forms of conditioned reflex manifestation. Three types of reactions were considered: A--decrease of respiratory movements amplitude towards the end of the studied interval between reinforcement; B--increase of the amplitude; C--food-procuring paw movement a few seconds before the reinforcement. All three forms of the conditioned reflex to time differed from each other by the level of increase of functional connections number by the moment of the reinforcing stimulus action, and also to a greater extent by the frequency of occurrence of intervals in which the sum of neuronal connections in all simultaneously recorded microareas was greater in the "active" phase than in the "inactive" one. These parameters did not always correlate with the change of impulses frequency of separate neurones which occurred considerably more seldom. All the observed changes were manifest significantly more often when the animals performed the instrumental food-procuring movement than during changes of only the respiratory movements amplitude.     

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.     

The character of the background spike activity of cortical neurons under the influence of psychotropic drugs]

A comparison was made on alert rabbits between the nature of spike activity of normal cortical neurones and of those after a two-week daily administration of neuroleptics, namely chlorpromazine, trifluoperazine and haloperidol in 1 and 5 mg/kg doses. The groups of neurones did not differ in the mean frequency of firing. However, the use of the main components method and of cluster analysis showed considerable differences between neuronal activity following the action of neuroleptics and that in control animals. The most common effect of neuroleptics consisted in a reduction of the number of low frequency neurones with burst discharges and small dispersion of distribution of interspike intervals. Trifluoperazine and especially haloperidol differed from chlorpromazine in that they brought about an appearance of cortical neurones for which the distribution of interspike intervals had an almost symmetrical form and a mode of 80--170 msec. After the action of haloperidol about a third of the neurones had a mode up to 10 msec. An assumption has been made that the major effect of trifluoperazine and haloperidol consists in an increase in the reverberative activity of the brain.     

Neuromediator sensitivity of neurons of the reticular formation and orbital cortex in hungry and satiated rabbits

In conditions of stereotaxic fixation, noradrenaline microionophoresis and stimulation of the lateral hypothalamus acted in the same sense on impulse activity of 35 and 37% of the neurones in the reticular formation of satiated rabbits, in joint action increasing the number of cells with distribution of intervals characteristic of alimentary motivational excitation. Microionophoresis of acetylcholine to the neurones of the orbital cortex in freely behaving rabbits reshaped the impulse activity of 57% of cells in accordance with the pattern of discharge activity characteristic of alimentary motivational excitation. Such excitation, natural as well as artificially evoked, widens polychemical properties of the neurones of the reticular formation and, on the contrary, narrows polychemical properties of the nerve cells of the orbital cortex.     

The role of motivation in the performance of a conditioned switching-over of the maze habit in ants Myrmica rubra after a change in the quality of the food reinforcement

Active foragers Myrmica rubra were trained in a maze under conditions of different levels of colony need in food with carbohydrate (sugar syrup) or protein (ants Lasius niger pupae) reinforcement. Acquisition of the maze habit was better under conditions of reinforcement with pupae, especially by its time indices. Ants were able to modify the acquired habit when the reinforcement quality was changed. It was shown that learning was possible only when the colony and after a change pupae for the syrup was "hungry". Under these conditions, after a change of the syrup for pupae or visa versa the previously acquired optimum habit was transferred. Several hours later, with satiation of the colony, food reactions learned with protein reinforcement switched-over to "stochastic" non-optimized behavior with the dominance of exploratory reactions. Thus, it was shown that higher social insects ants were capable for conditioned switching-over. Different forms of this phenomenon depended on the level of the colony need in food and, consequently, on the level of the social food motivation of foragers ants.     

Impulse activity of neurons of the visual and somatosensory regions of the cerebral cortex at different stages of goal-directed behavior

Impulse activity of neurones of the visual and somatosensory cortical areas was studied in free moving cats during performance of conditioned instrumental food-procuring reactions to the presentation of light or sound. It was established that the units of these cortical areas may participate in both all or individual stages of complex instrumental behaviour. The visual cortex neurones are more extensively involved in the formation of successive stages of the goal-directed behavioral act. Significant differences were revealed in the unit responses of the visual and somatosensory cortical areas at the moment of the switching on of the conditioned signal, at the period of "reinforcement anticipation", at the moment of appearance of milk, the reinforcing agent, and during reinforcement, when the milk was lapped by the animal.     

Participation of frontal lobe neurons in the organization of successive inhibition and disinhibition of conditioned reflexes in the dog

Neuronal activity in g. proreus was studied during classical secretory conditioning and its differentiation in dogs. Three types of changes in neuronal reaction pattern were identified during differential conditioned stimulus compared to the pattern observed during positive conditioned stimulus. It has been shown that signal significance of the conditioned stimulus may be coded by specific distribution of interspike intervals in response to different conditioned stimuli. In situation of successive inhibition or disinhibition of the differentiation some neurones displayed simultaneous appearance of interspike intervals specific for responses to current and previously presented conditioned stimuli.     

Synchronization dynamics in the neuronal work of the neocortex and hippocampus during learning before and after the administration of nootropics and narcotics

The basal difference in action of the studied drugs was that nootropics (phenybut in a dose of 40 mg/kg and pyracetam in a dose of 200-400 mg/kg) did not change the initial action of pain reinforcement on synchronism in responses of the cortical neurones of alert nonimmobilized rabbits by inhibitory type (coincidence of the presence and absence of impulse activity) towards its decrease, while narcotics of various types (ethanol in a dose of 4-6 mg/kg, morphine-like opiate DAGO and opioid peptide DADLE in doses of 250 mkg/kg) eliminated the action of pain reinforcement on synchronism in responses of the cortical neurones both by inhibitory and activation (time of coincidence only of the presence of impulse activity) types. These and other drugs mainly weakened the initial action of both the inhibitory and reinforced light flashes of synchronism in neurones activity both by inhibitory and activation types. There was no constant parallelism between changes of synchronization and the frequency of the cortical impulses.     

The dependence of the neuronal reactions of the sensorimotor cortex to a simultaneous complex stimulus on the level of the differentiation of its components]

On alert animals the change was studied of the neuronal activity of the sensorimotor cortical area of cats brain in dependence on the level of differentiation of the components of simultaneous heteromodal complex stimulus. According to the character of this dependence and a number of other parameters two groups of neurones were singled out in the sensorimotor cortex. It was shown that parameters of reactions of all recorded neurones of the sensorimotor cortex to the positive conditioned signal were the first established after consolidation of the animal conditioned motor activity. In the course of elaboration following parameters changed: expressiveness, intensity, duration and value of latency. Reactions of neurones of both groups to the inhibitory stimuli were stabilized only after consolidation of the habit of differentiation. Responses of the first group neurones changed only by the pattern of discharge, while the responses of the second group neurones could change by expressiveness of response, its sign, duration and value of latency. Oscillations of the differentiation level after finishing of the elaboration of inhibitory conditioned reactions affected only the responses of the second group neurones to complex components.     

Convergent properties of 3 types of visual cortex neurons recorded with various action potential amplitudes

Responses of visual cortex neurones recorded with large (N1), mean (N2) and small (N3) amplitudes of action potentials to photic, acoustic and electro-cutaneous stimuli were studied. It was shown that N1 neurones as differing from N3 were predominantly polymodal, often reacted with inhibitory responses and their background activity was characterized by random distribution of interstimuli intervals. Inputs for heteromodal stimuli were found to differ in N1 and N3 neurones. The results suggest existence of functional heterogeneity of neurones, recorded with different action potential amplitudes.     

Effect of thyroliberin on membrane potential and pattern of spontaneous activity of neurons of the respiratory center in rats in vitro

On frontal brainstem slices of rat by means of whole-clamp recordings, we investigated effects of TRH (10(-8) [symbol: see text]) on membrane potential and firing pattern of the neurones in ventrolateral area of the solitary tract nucleus and pre-Botzinger complex. TRH induced a membrane depolarisation and an increase in spontaneous activity of the respiratory centre neurones. After TRH administration, a shortening of time intervals between the beginning of bursts was found in bursting neurones of the pre-Botzinger complex. In some silent neurones, TRH elicited appearance of firing activity, so the silent neurones of the solitary tract nucleus were transformed into tonic while the silent pre-Botzinger complex neurones were transformed into bursting ones. Thus, there is a direct regulatory effect of TRH on the respiratory centre neurones at the level of their membrane.     

The characteristics of the neuronal reactions of the cat somatosensory cortex to a heteromodal complex conditioned signal]

On alert cats the change was studied of the activity of the neurones of the sensorimotor cortical area at instrumental reaction to a simultaneous heteromodal complex stimulus. It was shown that in the projection of distal limb areas a group could be singled out of neurones, which changed their activity in one direction depending on the character of presented signals. In these cells an increase of discharges frequency was observed in response to complex stimulus, consisting of light and sound signals. After the extinction of the motor reaction both to the complex stimulus and to its components neuronal reactions of lesser intensity was recorded, what determined the absence of the motor reaction. This group of neurones had receptive fields localized on distal limb areas, it was activated at fulfillment of the movement of catching the reinforcement and belonged to neurones of the pyramidal tract. The neurones with receptive fields on the whole limb surface or changing their activity at the animal pose change, had variable reactions to positive and differentiation stimuli.     

Possible mechanisms of the divergent effects of ACTH4--10 and its analog containing the D-isomer of phenylalanine on behavior

The effect of two oligopeptides--ACTG4-10 and hexopeptide met-glu-his-D-phen-lis-L-phen (Dphen-GP) on memorizing the situation and on orienting-investigating reaction was studied in albino rats by the method of elaboration of food-procuring habit in T-maze and by the method of "open field". It was shown that these peptides in a dose of 15 mcg/kg with certain periods of administration, have an opposite effect on maze learning but a similar effect on memorizing in the "open field". ACTG4-10 slightly increases motor activity in the "open field", whereas Dphen-GP decreases it considerably. It is suggested that ACTG4-10 improves the formation of trace processes independently of the sign of reinforcement, whereas Dphen-GP selectively enhances defensive reaction and memorizing, connected with negative reinforcement.     

Conditioned reactions of hippocampal neurons during amphetamine poisoning and its counteraction with haloperidol

Activity of 144 neurones of the dorsal part of the rabbits hippocamp was recorded during elaboration of motor conditioned reflex to time. Chronic amphetamine intoxication lowered the ability of hippocampal neurones to form conditioned reactions in response to pairings of sound stimuli with electrocutaneous reinforcement and fully suppressed mechanisms of reproduction by cells of engrams of previous pairings in series of their omissions Single administration of haloperidol to intact animals somewhat increased the number of neurones reacting to the pairing and their omissions in conditioned reflex to time without significantly influencing the intensity and dynamics of reproduction of endogenous cellular reactions in the series of consecutive omissions of pairing. Haloperidol administration during amphetamine intoxication elicited shifts towards normalization of conditioned activity of neurones, eliminating the suppressing action of amphetamine on mechanisms of reproduction of engrams of combined stimuli. Such "therapeutic" effect of haloperidol in many cases did not depend on the character of its psychotropic action. The properties of amphetamine and haloperidol action on the cells of the hippocamp are discussed as compared to their action on the neurones of other brain structures, previously studied in an analogous experimental situation.     

The dynamics of the activating and inhibitory types of cortical neuron synchronization during the realization of a defensive reflex and internal inhibition

In the visual and sensorimotor areas of the neocortex and in the hippocampus of alert nonimmobilized rabbits, in response to combinations of light flashes with electrocutaneous limb stimulation an increase was observed of synchronization in the activity of the near-by neurones by activation by inhibitory type (coincidence of the presence and absence of impulse activity). In response to flashes against the light background--conditioned inhibitor--in the visual cortex synchronization of neurones increased by inhibitory type, and in the sensorimotor cortex and hippocampus changes of synchronization appeared, similar to the action of pain reinforcement but considerably weaker. The increase of synchronization by the activation type took place mainly in the neurones pairs with unidirected increase of impulses frequency and by the inhibitory one--with its decrease. Along with this, in a considerable part of neurones pairs both changes of synchronization appeared at the impulses frequency changes of different direction.     

Tonic component of the conditioned reflex process and its functional role

Tonic background activity of 266 neurones in the hippocampus and different neocortical areas was studied in freely moving rabbits in the process of defensive and food instrumental conditioned performance and during switching-over of instrumental and classical food and defensive reflexes. Associations of CS and reinforcement evoke background activity changes in most of recorded cortical neurones preceding the development of other conditioned manifestations. Conditioned reflex was performed only after reaching the background firing rate of almost every examined neurone optimal for its realization. The performance of different conditioned reflexes was associated with different background activity levels of cortical neurones. The above mentioned data form the experimental basis for the identification of the tonic component in conditioned process which reflects tonic character of temporary connection formation and function.     

Spontaneous discharge patterns of mesencephalic neurons: interval histogram and mean interval relationship

Summary The spontaneous nerve impulse activity of 354 neurons of the mesencephalic reticular formation resp. the superior colliculus of unanesthetized curarized rats resp. cats has been recorded by microelectrodes and processed by means of a LINC computer. A relationship between the shape of interimpulse interval histogram (IH) and the mean interimpulse intervals (MI) of the same spike train has been found. Neurons with long MI's (low frequency of firing) are never characterized by symmetrical IH's, the exponential IH (characterizing random occurrence of impulses) being the most common in these cases. Neurons with symmetrical IH's are usually those with short MI's (fast firing rate). Longlasting recordings with changing MI show that the shape of IH's may not be considered in general a stable feature of certain neurons (in the majority of cases it changes together with the MI). Neurons with symmetrical IH's and short MI's may not be found in the superficial layers but in the depth of the superior colliculus only (having probably like the reticular formation integrative functions). A computer model is presented explaining the observed dependency of the IH shape on the MI duration in terms of the change in the mean frequency of common input process.     

Behavioral specialization of cortical and hypothalamic neurons in the rabbit

Behavioural specialization was analyzed of hypothalamic and limbic neurones, with their activity recorded in rabbits during food-acquisition behaviour. The neurones with activity changed during staying of the animal in a definite place of the cage or during behavioural acts, characteristic of a specific behaviour in the cage, are considered as specialized in relation to the most "new" systems, acquired by the rabbit directly during learning of the given behaviour. Neurones with the activity changed with rabbit's turns, i.e. connected with behavioural acts, which the rabbit has not specially learnt, are considered specialized in relation to more "old" inborn systems. Neurones, in which no constant connection with any part of the studied behaviour was observed, are related to the most "ancient" systems. Comparison of the number of hypothalamic and limbic neurones of different groups showed that in the cortex there were some more neurones specialized in relation to behavioural acts, which were formed directly during learning of the rabbit in the experimental cage.