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 piracetam plus choline treatment on hippocampal rhythmic slow activity (RSA) and behavior in rabbits

The effects of chronic treatment with piracetam (100 mg/Kg) plus choline (100 mg/Kg) on rabbits' hippocampal electrical activity and behavior have been studied. Animals were exposed to a neutral environment, in the absence of any external stimulus, and then to an object and a stuffed sparrow-hawk. Results show a drug related reduction in the amount of the hippocampal rhythmic slow activity (RSA) and an increase in RSA high frequency values in the presence of the object and of the stuffed animal, but not in the neutral environment. This would suggest that piracetam plus choline treatment has an effect on RSA in situations in which selective attention is required.     

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.     

Intranasal epitalon infusion modulates neuronal activity in the rat neocortex

Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of pineal peptide extract, have been studied. The intranasal infusions: a noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier, was used. The aim of the study is to estimate epitalon action on rat motor cortex spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg). Extracellular unit recording was made using glass microelectrodes (1-2 MOhm). After recording of spontaneous activity (10-15 min), epitalon intranasal infusion (2 ng) was followed by 30-minute recording. Within a few minutes after the infusion, significant activation of neural activity was observed (2-2.5-fold higher frequency of neuronal spikes). Complex response consisting of several phases was identified in some recordings. The spikes frequency growth during 5 to 7 min (first phase) after the infusion was followed by the second (11-12 min) and the third (17-18 min) phases. An increase of neuronal spontaneous activity was conditioned by the higher frequency of already active units and by the involvement of previously silent cells. At least the first phase of epitalon action can be explained by direct action of the peptide on the cells of the motor cortex.     

Influence of anxiolytic afobazole on amygdalar neuronal activity and behavior of rabbits in emotionally negative situations

The influence of systemic injection of anxiolytic afobazole (1 mg/kg) on interaction between neurons of the basal and central amygdaloor nuclei and behavior of rabbits in negative emotional situations was studied in order to reveal characteristics of amygdalar neuronal network properties during unconditioned fear. An afobazole injection results in a prolongation of stay in the light compartment of dark-light chamber, in a decrease in freezing probability after exposure of emotional stimuli, in appearance of some aggressive reactions in open field. Behavioral alterations were accompanied by duration increase and latency changes of amygdalar neuronal inhibitory interactions, by increase of probability of neuronal interactions on delta-range frequency, by decrease of interactions on theta-range frequency. Under the influence of afobazole the asymmetry with right dominance in interhemispheric interaction of amygdalar neurons decreased. Changes in network properties ofamygdalar neurons during afobazole injection testify to reduction of activation level of this structure taking place at the expense of enhancement of inhibitory interactions between neurons.     

Conjugation of the neuronal impulse activity in the rabbit neocortex during self stimulation of the lateral hypothalamus

Correlation of impulse activity of visual and sensorimotor neurons of both hemispheres in 10-s interval after self-stimulation of the right and left lateral hypothalamus was studied by plotting cross- and autocorrelation histograms. The number of cell pairs, in which sensorimotor neurons discharged after visual ones, increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the alpha- and theta-range in crosscorrelograms increased; the alpha frequency increased mainly in the right hemisphere, while the theta frequency increased in the left hemisphere. The interhemispheric asymmetry in the interaction between cortical neurons was not associated with the side of hypothalamic stimulation.     

The neuronal activity of suspension grafts of the neocortex]

Were compared electrophysiological characteristics of suspension (SUS) and solid (SOL) tissue grafts of embryonic neocortex transplanted into the barrel field of adult rats. The level of survival of SUS and SOL grafts did not differ significantly (89% and 95% correspondingly). All SUS grafts were integrated with the host brain judging by histological and electrophysiological criteria. Reactivity of neurons to electrical stimulation of the recipient's brain and to sensory (tactile) stimulation, as well as the latencies of on-responses were similar in both types of the grafts. However, proportion of neurons with on-responses was nearly twice lower in SUS grafts, while the number of neurons responding to tactile stimulation by primary suppression of activity was significantly higher than in SOL ones. It is suggested that the derangement of primary architectonics unavoidable during preparation of suspensions is responsible for the described differences between SUS and SOL grafts.     

Coordination of neuronal activity by gap junctions in the developing neocortex

During embryonic development, gap junctions link cells into functional communication compartments characterized by a common development fate. Increasing evidence for gap junctions between immature neurons suggest that similar mechanisms may also be at work in the developing vertebrate brain, where gap junction-coupled neuronal assemblies often precede synaptically-linked functional networks. Recent experiments in the developing mammalian neocortex demonstrated the presence of gap-junction mediated second messenger waves, similar to those in non-neuronal cells. The primary function of neuronal gap junctions, therefore, might be to coordinate biochemical activity, rather than to act as purely electrical synapses. Thus, gap junctions may serve to amplify neuronal activity produced by weak synaptic stimulation.     

Interhemispheric asymmetry of neocortex and hippocampus in orienting exploratory behavior of rabbits

Correlation of discharges of cortical neurons in symmetrical points of the visual and parietal cortices and left and right hippocampal CA1 neurons was studied in freely moving rabbits during exposure to emotional stimuli. Crosscorrelation histograms were plotted. As compared to the initial state, during an active orienting exploratory reaction to stimuli, the left-side influence on right-hemispheric cortical neurons with a delay about 100 ms increased, which led to asymmetry in interhemispheric interaction with the left-side dominance. During freezing, the left-side influence became weaker, and the effects of the right hemisphere prevailed. Hippocampal asymmetry in neuronal activity was in reciprocal relationship with neocortical asymmetry. In the hippocampus, the right-side influence with a delay about 200 ms increased during the active exploratory reactions resulting in the right-side dominance. Freezing was accompanied by strengthening of the left-side influence (the left-side dominance). During the active locomotion, neuronal interaction in the hippocampus was predominantly realized in the theta-range frequency, whereas freezing was characterized by the delta-range correlation. It was concluded that the active or passive nature of a behavioral reaction to emotional stimuli was correlated with changes in asymmetry in the interhemispheric neuronal interactions at the cortical and hippocampal levels.     

Mechanisms of epileptogenic effects of some convulsants on the neuronal activity in the neocortex

The data obtained in the studies of neurophysiological aspects of epileptogenesis in the brain cortex, which have been carried out in our laboratory for many years, are used for the analysis of epileptogenic effects of a few convulsants (penicillin, strychnine, and d-tubocurarine) on the activity of neocortical neurons. It has been demonstrated that the development of the epileptiform activity in the cortex is accompanied by suppression of IPSP, and the above convulsants directly influence the mechanisms of postsynaptic inhibition. Epileptogenic effects of strychine and penicillin are based on blocking of chloride ion channels and depend on the direction of chloride currents. The role of excitatory and inhibitory synaptic interactions among neurons in generation of the epileptiform activity is discussed.     

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.     

Effect of arecoline on neuronal activity in the posterior hypothalamus of rabbits with experimental fever

It has been found in experiments on unanesthetized rabbits that arecoline administered to the lateral ventricle of the brain produced an action which was opposite to that of leukocytic pyrogen. It inhibited the activity of individual neurons of the posterior hypothalamus and decreased the body temperature, with this decrease being attended by the signs of intensified heat emission. Arecoline injection coupled with the central action of PGE2 was followed by an increase in the neuronal activity in the posterior hypothalamus and reduction of hyperthermal response.     

Effect of piracetam on the habituation of the neuronal cholinoreceptor membrane of the edible snail

Piracetam is shown to modulate the habituation pattern of cholinoreceptor neuronal membrane in Helix lucorum. Piracetam (10(-2) M) intensified the reversible decrease of depolarization and spike discharge induced by the local microionophoretic rhythmical application of acetylcholine to the neuron soma. The ability of piracetam to intensify the habituation of neuronal cholinoreceptor membrane may serve as a model of its facilitating effect on the development of habituation of behavioural reactions. Piracetam (5.10(-2) M) was shown to induce a shift in the membrane potential towards depolarization in the majority of identified neurons studied.     

Structure of background neuronal activity in thin slices of guinea-pig neocortex

We recorded background neuronal discharges extracellularly in guinea-pig cerebral cortex slices maintainedin vitro. The following types of activity were delineated: 1) regular single discharges (38.5%), 2) irregular spikes (6.5%), 3) bursts (6.5%), 4) burst-and-single discharge (mixed) activity (26.5%), 5) group discharges (2.5%), 6) multicellular volleys (18.5%). Each of these types corresponds to a characteristic distribution of interspike intervals in the form of an autocorrelogram. Regular pacemaker-type discharges, which are never observed in normal or isolated cortex, appeared in small volumes of grey matter and in the absence of afferentation.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 441–449, July–August, 1985.     

Effect of electrical stimulation of the hippocampus and neocortex on cingulate cortical neurons in rabbits

Extracellular unit activity of the anterior and posterior zones of the cingulate cortex and also of the anterior and posterior cortical association areas was analyzed in unanesthetized rabbits. In the posterior zone considerably more cells (60%) responded to hippocampal stimulation than in the anterior zone (18%). In 43% of these cells in the posterior zone but only in 5% in the anterior zone, the responses followed the frequency of stimulation. Unit responses in the posterior zone could be divided into two discrete groups: those with short (12.3 ± 6.5 msec) and those with long (50.2 ± 10.0 msec) latent periods. Inhibitory phenomena also were well marked during hippocampal stimulation. More than one-third of cells of the cingulate cortex responded to stimulation of the posterior association zones by spikes which followed the stimulus, and by subsequent inhibition. Responses of this kind to stimulation of the anterior association zones were found in only a few cells in the anterior zone of the cingulate cortex. The results are discussed in the light of data from morphological investigations relating to connections between these structures.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 270–277, May–June, 1982.     

Cyclin-dependent kinase 5 and neuronal migration in the neocortex

The cyclin-dependent kinase 5 (Cdk5) plays an important role in the proper establishment of neocortical layers. Over the past several years, key molecular targets of Cdk5 have been identified that show intriguing connections to the adhesional and cytoskeletal components of cell movement. This molecular knowledge about Cdk5 signaling has begun to translate into an understanding of how Cdk5 regulates the cellular physiology of neocortical layer formation. Together with recent progress on the signaling relationship between Cdk5 and Reelin, the other key protein involved in neocortical layer formation, and their relationship to migration modes, research on understanding neocortical layer formation has arrived at a most promising crossroad.