Pentagastrin modulation of the neuronal sensitivity of the lateral hypothalamus to noradrenaline and dopamine

Experimental study is dedicated to mechanisms of interaction of pentagastrin and monoamines (noradrenaline and dopamine) at the level of single neurones of the rabbits lateral hypothalamus under alimentary motivation and under saturation. It is shown that pentagastrin can modulate the effects of noradrenaline and dopamine on neuronal impulse activity in hungry and fed up animals, and the character of its action depends on the rabbits initial state. It is suggested that pentagastrin is a factor initiating alimentary motivational excitation, while noradrenaline maintains the latter at the definite level up to obtaining useful result by the animal, when dopaminergic mechanisms participating in the process of reinforcement join the noradrenergic ones.     

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.     

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.     

Elementary transcallosal connections of the rabbit sensomotor cortex]

Antidromic responses of two callosal neurones to a local electrical stimulation of the rabbit sensorimotor cortex may be recorded simultaneously with one microelectrode in the homotopic cortical area. In such recording conditions the relative amplitude of extracellularly recorded action potentials of the two neurones is determined primarily by the distance between these neurones and the electrode's tip. In response to the stimulation of the symmetrical area transcallosal monosynaptic excitation of the callosal neurone may occur; two callosal neurones may exite monosynaptically one and the same recorded neurone. The results suggest the existence of clusters or columns, formed jointly by the bodies and terminals of callosal neurones; a functional interconnection between symmetrical clusters or columns may exist, in particular a positive feedback.     

Effect of stimulation of the reticular formation on the motivational and reinforcing effects of the self stimulation zones

The influence was studied on the midbrain reticular formation (RF) on motivational and reinforcing effects of stimulation of the same selfstimulation zones (SS) of hypothalamic area. A current of gradually increasing intensity was used, by means of which three groups of functionally (behaviourally) specific reticular points were revealed: motivationaly neutral, positive and negative. The data obtained show that influences of RF on SS zones of hypothalamus differand depend on functional properties of various RF areas. Changes of motivational effects in SS zones reflex the specificity of reticular foci in a lesser degree than changes in reinforcing effects. It has been suggested that reinforcing effects of the SS hypothalamic zones possess their own activating mechanism specifically related to its "positive" link and differing from reticular mechanism of unspecific activation.     

Interaction of brain macrostructures during organization of behavior

The data on anatomical connections, injury consequences, summate and unit activity records may be represented as a chain of events running in sequence and in parallel in the brain of higher mammals. Internal (metabolism) and external (odour, pain, etc.) incentive unconditioned stimuli activate motivational structures of the hypothalamus, which in turn activates the frontal areas of the neocortex and the hippocampus. In case of coincidence of earlier neutral external stimuli with the action of reinforcing unconditioned ones, the hippocampus becomes the first place of convergence of combined afferentiations. After formation of the act, those external stimuli or their engrams which have been accompanied earlier by satisfaction of a certain need, are selected as a result of joint action of the hippocampus and the frontal cortex. By comparison of motivational excitation with available stimuli or their engrams retrieved from memory with the participation of the temporal cortex, an emotional colouring of the stimuli and engrams is formed in the amygdala leading to isolation of a dominant motivation, destined to be satisfied in the first instance. The program formed in the frontal cortex, comes to the basal ganglia where, by means of interaction with the parietal cortex, it confirms to the spatial coordinates of the forthcoming action. From the fronto-striate system, the excitation comes through the motor cortex to the effector organs accomplishing the behavioural act.     

Changes in the configuration of conditioned reactions of visual cortex neurons during changes in reinforcement parameters]

In order to study the influences of controlled changes of defensive integration on the activity of visual cortical units their responses to a conditioned light flash and electric cutaneous stimulation with a 600 msec interval between them were recorded in experiments on alert rabbits. It has been shown that in a third of the neurones the types of reaction to light flashes and electric stimuli coincide. The changes in parameters of the reinforcing shock led to a changed response of most cells to the conditioned photic stimulus and electric stimulation. The changes may have affected units which produce any activation phase, including cells with activity characteristic of detectory ("simple" and "complex") visual neurones. The data obtained suggest that the special function of the visual cortex is used in different ways in systemic mechanisms of conditioned and unconditioned defensive acts and that the integrated system of a behavioral act exerts control both on the use of the unit in a certain systemic process and on its receptive field.     

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.     

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.     

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.     

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.     

Does the destruction of the catecholaminergic neurons in newborn rat pups influence the modulatory function of the cholinergic system?]

On outbred ratlings aged 21-31 days the influence was studied of the destruction of catecholaminergic (CA) system on the reactions of the neurones of the cortical somatosensory zone, elicited by the stimulation of the ischiatic nerve and modulation of these reactions after stimulation of the basal nuclei area (the source of the neocortex cholinergic innervation) and acetylcholine (ACh) microiontophoretic application. It is shown that destruction of CA system in newborn ratlings increases the reactivity of the somatosensory cortical neurones in 21-31 days old animals to sensory stimulation; it does not influence the efficiency of modulating action of the cholinergic system of the forebrain and leads to the increase of modulating influence of the applicated ACh. It is postulated that as the result of perinatal destruction of CA brain system, in the neocortex a specific morpho-functional organization is formed of structures and processes at which the modulating function of the forebrain cholinergic system turns out, by quantitative criterion, at least, to be compensated.     

The cholinergic system of the forebrain modulates the activity of the GABA-ergic interneurons which realize presynaptic regulation in the neocortex of kittens

It has been found that at the end of the second week of postnatal life, stimulation of cholinergic ascending paths causes a selective inhibition of cortical neurones reaction to sensory stimulation, without influencing the background activity. The observed inhibition is blocked both by atropine and picrotoxin, but not by bicuculline. It is suggested that the observed phenomenon characterizes, presynaptic control of cortical neurones activity in the early ontogenesis. This inhibition is formed on the basis of cooperative choline- and GABA-ergic brain systems participation and is performed not through GABA-receptors.     

Analysis of the impulse activity of the cerebral neurons in rabbits with artificial thirst

Neuronal impulse activity of various brain structures was studied in rabbits in conditions of artificial thirst elicited by intrabrain injection of 0.3-0.5 M NaCl solution (from 5 to 8 mcl). Specific organization was revealed of the impulse flow at drinking motivational excitation, i.e., domination on interval histograms of certain intervals (20-40 and 100-200 ms). Comparative analysis of activity patterns of both different and the same neurones in conditions of natural and artificial thirst showed a resemblance of dominating intervals values that testifies to specificity of the observed neural activity characteristics, reflecting drinking motivational excitation. Thus, an interval code is found corresponding to drinking motivational state. P. K. Anokhin's notions about anticipating reflection of reality find their expression in anticipating reactions of brain neuronal activity.     

The dominant motivation in the mechanisms of the conditioned reflex

It is substantiated that the mechanisms of dominant motivations play an essential role in conditioning. It is shown that motivations change convergent and chemical characteristics of single neurons of different brain structures and, especially, their sensitivity to corresponding reinforcing stimuli. As a result, motivation plays a role of an initial "canvas", against the background of which molecular "engrams of reinforcement" are built. The processes of interaction between the dominant motivation and reinforcement are mainly addressed to the apparatus of the action result acceptor. It is shown that dominant motivations participate not only in construction of molecular reinforcement engrams but also in their forestalling retrieval.     

Morphofunctional characteristics of the associative region of the cerebral cortex in experimental neuroses in the dog

Ultrastructure of neurones and synapses of the cortical associative area of dogs has been studied under conditions of experimental neuroses caused by prolonged informational loads with constant time deficit and high motivational signals significance. Analysis of subcellular reorganization of a number of neuronal and synaptic organelles showed the degenerative changes of afferent conducting systems in various neuropil parts leading to the falling out of definite neuronal groups from stable functional connections and to the disturbance of intracortical interrelations. In the cortex simultaneously with destructive processes, are developing intracellular compensatory-adaptive reactions.     

Callosal neurons: monosynaptic connection between them and their descending projections

Antidromic and monosynaptic unit responses to the stimulation of the corpus callosum and the symmetrical cortical area as well as antidromic responses to pyramidal tract and thalamic nuclei stimulation were recorded in the sensorimotor cortex of unanaesthetized rabbits. Out of 182 callosal neurones 13 exhibited transcallosal monosynaptic responses. 8 out of 56 callosal units responded antidromically to pyramidal tract or thalamic stimulation. Thus callosal neurones may be monosynaptically excited by callosal units via the corpus callosum and by the pyramidal tract units. It was also found that a pyramidal tract neurone may send a collateral through the corpus callosum and at the same time have a transcallosal monosynaptic input. The role of monosynaptic transcallosal excitation of callosal neurones is discussed.     

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.     

Changes in the activity of rat cortical and hippocampal neurones after the iontophoretic administration of beta-endorphin, glutamate and GABA

The effect of microiontophoretically administered beta-endorphin on the activity of 62 cortical and hippocampal neurones was studied in acute experiments on 14 rats. The effectiveness of beta-endorphin was first of all verified in the isolated guinea pig ileum, the mouse was deferens and in a study if its analgetic and catatonic effect in rats. Beta-endorphin only mildly depressed the spontaneous activity of cortical neurones, but markedly inhibited the activity stimulated by the microiontophoretic administration of glutamate. In the hippocampus, beta-endorphin stimulated the activity of all the studied neurones when only low ejection currents were used and activation persisted for 1-4 min after terminating administration. With higher ejection currents, the discharge frequency rose enormously and not even GABA blocked this effect. The excitatory effect of beta-endorphin on the hippocampal neurones may possibly be the basis of the epileptogenic action of this substance.     

Interaction between morphine and putative excitatory neurotransmitters in cortical neurons in naive and tolerant rats.

Microelectrophoretically applied morphine depressed spontaneously discharging cortical neurones of rats and blocked excitation induced by electrophoretic administrations of either acetylcholine or l-glutamate. This depressant effect and both the anti-acetylcholine and the anti-glutamate effect were naloxone antagonizable and therefore regarded as specific morphine actions. The excitatory effects of morphine were not affected by naloxone application and were classified as non-specific.In chronically morphinized rats the depressant effect of morphine on spontaneous discharge activity and also its blocking action upon acetylcholine and l-glutamate-induced excitation were almost completely abolished. The predominant response in such pre-treated animals was non-specific excitation. Acetylcholine and l-glutamate were found to be more effective in tolerant rats (supersensitivity).