Effect of piracetam on the neuronal activity of the neocortex and on behavior in rabbits during learning

Against the background of the action of piracetam--a cyclic derivative of GABA--in a dose of 200-400 mg/kg, no significant changes were observed of probabilities of motor reactions to inhibitory and reinforced light flashes. Piracetam in that dose did not affect inhibitory pauses in responses of neurones in the visual area and corresponding late components of the evoked potential to nonreinforced light flashes, i.e. it did not intensify inhibitory hyperpolarization processes in the cerebral cortex. Piracetam administration improved differentiation of inhibitory and reinforced light flashes judging by bioelectric parameters of the brain activity as a result of intensification of pain reinforcement action on cortical neurones. The carried-out experiments revealed significant differences in neurophysiological mechanisms of action of piracetam and fenibut--GABA linear derivate related to nootropic class.     

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.     

Effect of ethanol on excitatory and inhibitory processes in the visual cortex of rabbits undergoing learning

Subcutaneous ethanol injection to waking rabbits in a dose of 2-6 g/kg causes discoordination of movements, a decline in motor reactions to inhibitory and reinforced light flashes, and appearance of equalizing and paradoxical relations in the number of reactions to these stimuli. Under the influence of ethanol, activating and disinhibitory action of the pain reinforcement on neurones of the visual area temporarily weakens, while the disinhibitory influence of light flashes (CS) is preserved. Judging from the dynamics of phasic reactions to the inhibitory light flashes, the ethanol in a dose of 2-6 g/kg does not influence the inhibitory hyperpolarization processes in the cerebral cortex of rabbits. Tonic inhibition of the cortical unit activity temporarily intensifies after the ethanol injection.     

Effect of the enkephalin derivative DAGO on neuronal behavior and activity in the neocortex and hippocampus of rabbits during the acquisition of conditioned defense and inhibitory reflexes

After subcutaneous injection of 25 mkg/kg morphine-like opiate--DAGO a decrease was observed of probabilities of rabbits movements at light flashes--defensive reflex signal. The level of the background neuronal impulse activity became gradually lower in the sensorimotor cortex and the hippocampus and did not change in the visual cortex. Decrease and restoration of responses to the reinforcing stimulus (electrocutaneous limb stimulation) in all studied cortical zones proceeded in one direction while there were significant differences in dynamics of responses to inhibitory and reinforced light flashes depending on the studied cortical zone and biological significance of the stimulus. Appearance is discussed of particular characteristics of neurones systemic organization during learning at change of reinforcement properties under the influence of the studied substance, as well as similarity of some features of mechanisms of internal inhibition elaboration in a defensive situation and of properties of positive reinforcement.     

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 substance P on behavior in the rabbit and the activity of cortical neurons during training

Subcutaneous injection of substance P to rabbits in a dose of 250 mcg/kg elicited a transitory disappearance of motor reactions to painful reinforcing stimuli and a reduction of their probability to reinforced and inhibitory light flashes, as well as a protracted heart rate increase and decrease of respiration rate. One third of the neurones recorded decreased their background firing level and or excitatory components of the reactions to reinforcement and conditioned light flashes. The decrease was most distinctly seen in the sensorimotor cortex and less pronounced in the visual cortical area and hippocampus. The influence of the substance P on different types of cortical inhibition was not the same. Tonic inhibition of neuronal activity in response to reinforcement was enhanced. Bioelectrical parameters which reflect an enhancement of inhibitory hyperpolarization during elaboration of internal inhibition (i.e. inhibitory firing delays and corresponding background and evoked slow potentials oscillations) were not changed.     

Comparison of spontaneous activity of mesencephalic reticular neurones in the waking state and during pentobarbital anaesthesia.

In rats immobilized by d-Tubocurarine the spontaneous activity of 100 mesencephalic reticular neurones was recorded extracellularly and statistically evaluated before and after repeated intravenous administration of 15 mg/kg doses of Pentobarbital. Number of spontaneously active neurones decreases quasi-linearly with repeated 15 mg/kg Pentobarbital doses. After a 75 mg/kg cumulative dose practically all neurones ceased firing spontaneously, whereas cortical EEG activity fully disappeared after the 90 mg/kg Pentobarbital dose. The firing rate was characterized by the mean interval with its standard deviation. Mean value for the total sample of spontaneously active neurones was 146.7 +/- 192.3 msec without Pentobarbital and increased to 302.7 +/- 367.5 msec after 15 mg/kg and to 400.6 +/- 452.5 msec after 30 mg/kg cumulative dose of Pentobarbital. The 15 mg/kg dose increased the frequency of firing in 5% of neurones only. The most often encountered type of interval histogram in the mesencephalic reticular formation was the exponential type (59% in unanaesthetized state), which was also most sensitive to Pentobarbital. Synchronized activity in bursts, characterized by periodical peaks and dips frequently occurred in neurones with the exponential-like interspike interval density after Pentobarbital administration. On the contrary, neurones with gamma-like and especially with symmetrical-like types of density were less influenced by Pentobarbital. In many neurones a periodical increase in the firing rate (with intervals of tens of seconds) related to the occurrence of spindles was present in the cortical EEG activity.     

The effect of acute alcoholization on the neuronal activity of the normal ventromedial hypothalamus and in pharmacological actions on the brain monoaminergic and opiate systems]

In experiments on white outbred male rats the specificity was studied of the influence and mechanisms of action of acute alcoholization (30%-solution of ethanol, intraperitoneally, 0.7 g/kg) on the activity of functionally different neurones of the ventromedial hypothalamus. Experimental results showed that the neurones, the activity of which lowered after saturation (I-st type), increased the discharges frequency at administration of ethanol. Nerve cells, the activity of which increased (II-nd type) and did not change (III-nd type) after saturation, had inhibitory character of reaction in response to alcoholization. The increase of serotonin content in the brain elicited by intraperitoneal administration of 5-OTPh (50 mg/kg) blockaded the action of ethanol on the nerve cells of the I-st type and did not change the effect of the alcohol on the neurones of the II-nd and III-nd types. Preliminary lowering of the noradrenaline level in the brain (disulphiram, intraperitoneally, 100 mg/kg) and blockade of opiate receptors (nalorphine, 5 mg/kg) fully eliminated ethanol influence on the activity of all types of neurones.     

The dynamics of the interimpulse intervals in the activity of sensorimotor cortex neurons during the acquisition of the food-procuring reflex in the rabbit]

State of hunger is characterized by the presence of definite distribution of interimpulse intervals in the activity of sensorimotor cortical neurones (SMC) of rabbit. Mostly bi- and three-modal distribution of interimpulse intervals in the background activity in hungry animals changes in the process of elaboration of food-procuring habit. As the habit consolidates, the SMC neurones acquire the ability to forestalling actions. Peculiarities are revealed of organization of the SMC neurones impulse stream in response to the action of conditioned signal in the case of abolition or substitution of the reinforcement. Repeated substitutions of reinforcement cause the formation of activity of concordance in the moment of substitute "recognition" despite the absence of alimentary reinforcement.     

Mechanisms of the effect of diazepam on paroxysmal electrical activity of an isolated cortical slab in cats

The effect of diazepam on paroxysmal global electrical activity of a neuronally isolated slab of auditory cortex and on inhibitory responses of its neurons due to intracortical electrical stimulation was investigated in cats. Diazepam (2 mg/kg, intravenously) caused inhibition of paroxysmal electrical activity and increased the number of inhibited neurons in both the acutely isolated slab and three weeks after isolation, compared with the intact cortex. However, the number of disynaptic responses was reduced under these circumstances, especially in the long-isolated slab. It is postulated that diazepam exerts its action through activation of GABA-ergic inhibitory neurons, by synchronizing inhibition and increasing the duration of the IPSPs. The action of diazepam is manifested first, probably, in the initial links of cortical neuron chains.I. I. Mechnikov Odessa State University. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 3–10, January–February, 1985.     

Characteristics of the neuronal reaction of the substantia nigra to nociceptive stimulation

The nature of neurone response of substance nigra (SN) to nociceptive stimulation of the cat's peroneal nerve has been studied. The recording of neurone SN firing rate revealed that the majority (71.0%) of the SN neurones responded to the nociceptive repetitive stimulation of the peroneal nerve. But the thresholds of nociceptive activation in SN neurones turned to be very high. As a result of it the number of SN neurones responding to repetitive peroneal stimulation was twice as many as the number of cells responding to single stimulation of the nerve. The intravenous injection of naloxone in dose 1.0 mg/kg changed both excitatory and inhibitory responses in majority (71.4%) of SN neurones responding to repetitive peroneal stimulation. Naloxone did not modify the firing rate of neurones nonresponsive to nociception.     

Relation of alcoholic motivation to the functional state of the emotive zones of the brain in rats

Reactions of neurones pair of positive and negative emotiogenic hypothalamus zones to electrocutaneous stimulation and to intraperitoneal administration of ethanol solution (2 g/kg) were studied in outbred male rats with previously determined attitude to alcohol. In animals who preferred alcohol the neurones of the negative zone were significantly more reactive, and in animals who preferred water the neurones of the positive zone were more reactive. In both studied groups of rats, in most cases ethanol had an inhibitory influence on impulse activity of negative zone neurones, but it acted differently on positive zone neurones: in most cases it intensified neurones impulse activity in rats preferring alcohol and significantly inhibited it in animals rejecting alcohol.     

Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

Experimental Data

Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult.

Mathematical Modeling

We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods.     

A neuronal analysis of the hunting behavior of sea butterfly Clione limacina]

Neurones of the cerebral ganglia controlling the movements of the hunting apparatus of predatory pelagic mollusc Clione limacina are described in detail. A large group is identified of high-threshold electrically interconnected neurones A, the impulse activity of which leads to the opening of the skin folds and throwing forward Clione catching tentacles. Neurones of B group, having constant background activity and receiving powerful inhibitory inputs from A cells, on the contrary, elicit contraction and drawing in of the hunting tentacles inside the head. The third group--C neurons, the impulse activity of which leads to tightening of the skin folds covering the hunting apparatus. The action has been studied on identified neurones of such transmitters as serotonine, dopamine and gamma-aminobutyric acid. Serotonine depolarises both A and B neurones, but activation of the hunting apparatus is an integrating effect: activated neurones A owing to powerful TPSP inhibit neurones B, interrupting direct exciting action of serotonine. Dopamine in different concentrations has an opposite effect: at low concentrations only B cells are activated and tentacles are drawn inside the head; at high ones the neurones A start working which inhibit B cells and activate the hunting apparatus. GABA renders to neurones, regulating the movements of the hunting apparatus a total, well coordinated action directed to activation of the hunting behaviour: it depolarises-activates A neurones and hyperpolarises-inhibits neurones of B and C groups.     

Effect of ethanol on central mechanisms of alimentary and defensive motivation in the rabbit

A single intravenous administration of ethanol (0.5 g/kg) to rabbits had different effects on the excitability of feeding and defensive motivational centers of the lateral and ventromedial hypothalamus. Ethanol abolished both inhibitory effects of the dorsal hippocampus and facilitatory action of the midbrain reticular formation on alimentary and defensive motivations. It elicited new power distributions of the main rhythms of general electrical cortical activity in the background and under stimulation of limbic-midbrain structures. Analysis of the activity of organello-specific enzymes in limbic-midbrain neurones revealed disturbances of cellular energetic processes caused by ethanol.     

Effect of a derivative of GABA, phenibut, on behavior and the activity of visual cortex neurons of the rabbit during elaboration of a defensive reflex and internal inhibition

In experiments on alert non-immobilized rabbits the effect of subcutaneous administration of the GABA-derivate--phenibut on behaviour, slow potentials and impulse activity of neurones of the visual cortex was studied during elaboration of a defensive reflex to light flashes and of conditioned inhibition. During the action of phenibut late negative-positive components of the evoked potentials to flashes, corresponding inhibitory pauses and postinhibitory activation gradually increased; then stable predominance of slow high-amplitude potential oscillations and corresponding neuronal group bursts appeared, separated by inhibitory pauses and in intersignal periods. Reinforcing stimulus, as before phenibut administration, lowered the amplitudes of slow potential oscillations and weakened inhibitory pauses in neuronal impulse activity. Dynamics of movements in response to the stimuli was of a phasic character. 3 hours after phenibut administration the discrimination of reinforced and inhibitory light flashes has distinctly improved. The obtained results confirm the initial concept of the significant role of the GABA-ergic inhibitory system in the process of elaboration of internal inhibition.     

Effect of sodium nitrite on the activity of the neocortex neurons during realization of defense and inhibition conditioned reflexes

A decrease in intensity and duration of short-latency reaction components of the sensorimotor and visual cortical neurons to specific stimuli (pain reinforcement and light flashes, respectively) was observed after the administration of NO-generating sodium nitrite (11 mg/kg, subcutaneously). Activation decrease in the visual cortex took place irrespective of biological significance of the light flashes, i.e., in case when this stimulus was a signal of defensive conditioning and in case when these flashes were applied with continuous light (a conditioned inhibitor). Sodium nitrite almost did not change the late activation of sensorimotor and visual neurons in response to pain reinforcement and disinhibitory action of the latter. The results confirm the viewpoint about different neurotransmitters in "specifically modal" and "non-specific" pathways to the neocortex during learning.     

Effects of clopheline on impulse activity of neurons in the midbrain and dorsal horn of the spinal cord

Clophelin (1-5 mg/kg) suppresses spinal dorsal horn neuronal nociceptive responses but does not change their touch stimuli reactions in unanesthetized curarized cats. This effect is steady to naloxone (1 mg/kg), yohimbine (5 mg/kg) and removal by prazosin (1 mg/kg). Clophelin depresses nociceptive responses of the central gray matter neurones which generalized pain impulses in the supraspinal structures.     

Cortico-subcortical interrelationships in the visual analyzer system at various stages of ontogenesis]

The influence of a corticofugal volley produced by single electrical stimulation of the visual projection cortical zone on the neuronal activity of LGB was studied in non-anaesthetized rabbits aged from three to thirty-five days. A coincidence was found between the time of appearance of nonspecific inhibitory corticofugal influences on the spontaneous activity of LGB neurons and the emergence of the first phasic-specific responses of the neurones of this level to a visual stimulus. It has been shown that the sensory flow at the LGB level can be controlled by non-specific inhibitory corticofugal influences at early periods of postnatal development. The appearance from the 15th day of life of specific responses to a corticofugal volley, including activation phases, leads to a greater complexity of the regulating Cortical influences on conduction of the afferent signal at the thalamic level. The data obtained are considered from the standpoint of integration of various levels of the visual analyser at different stages of ontogenesis.     

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.