Responses of neurons of the frontal area of the cortex of the rabbit to electric stimulation of certain limbic-mesencephalic structures after administration of substance P

In rabbits tested on behavioural reactions by electrical stimulation of certain limbic-midbrain structures, intravenous injection of substance P (30 mcg/kg) led after 10 min of silent period to a decrease of spontaneous neuronal activity in the frontal cortex. Convergence of excitations arising from the lateral hypothalamus, the dorsal hippocampus and the midbrain reticular formation was also found to decrease after the substance P injection. Analysis of neuronal responses allowed to establish that substance P markedly changed the ascending excitations of the lateral hypothalamus and was less effective for the influences from the midbrain reticular formation.     

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.     

Characteristics of memory and the functional organization of the hippocampo-reticulo-neocortical complex of the brain in the acute postoperative period

In tests on dogs, rabbits and rats, it has been established that in acute postoperative period, the time of memorizing of conditioned signals (light, tone and metronome) is reduced, the time of realization of conditioned reactions increases, the excitability and the bloodflow of the midbrain reticular formation and Mg-AtPhase activity of pons Varolii raise. In the hippocampus the excitability and local bloodflow lower and the activity of Ca-Mg-ATPhase is enhanced. In the frontal cortex these processes do not change. Functional interrelations of the brain structures in the acute postoperative period are characterized by the weakening of the activating influence of the reticular formation on the frontal cortex and an increase of its suppressive action on the dorsal hippocampus. It is suggested, that the discovered damages in the higher nervous activity are stipulated by the changes in neurochemical organization of the brain.     

Correlation between bioelectrical processes of the cortex, thalamus, midbrain reticular formation during formation of a defensive conditioned reflex in rabbits]

EEG power spectra of the sensorimotor area of the neocortex, the dorsal hippocampus, midbrain reticular formation and anteroventral thalamic nucleus, as well as corresponding coherence functions and phase spectra, undergo changes during formation and performance of defensive conditioned reflex in rabbit. The conclusion is draen that in the process of conditioning a morphofunctional system of brain structures is established including the above mentioned formations. Their functional integration occurs on the basis of theta-rhythm. The execution of a conditioned act requires isorhythmicity of electrical processes within the theta-range in the studied structures and an adequate level of their excitability, which is manifested in the dominance of 6,0 c/s frequency.     

Effects of pralidoxime applied locally into the midbrain reticular formation on the hippocampal theta rhythm induced by acetylcholinesterase inhibition

After local administration into the midbrain reticular formation of an acetylcholinesterase reactivator--Pralidoxime, a significant decrease of intensity of hippocampal theta rhythm induced by previous inhibition of acetylcholinesterase by DFP was observed already after 10 min. This result suggests that cholinergic structures are localized in midbrain reticular formation and that they play a role in the origin of hippocampal theta rhythm.     

Adaptive changes in the evoked electrical activity of the rat brain while training it in a controlled experiment]

A programmed change of a certain phase of cortical EP to a photic flash was reinforced in an unrestrained chronically operated animal (a rat) in the course of an operant controlled experiment. A painful subcutaneous stimulation or stimulation of the emotionally positive zone of the lateral hypothalamus was used as a reinforcing agent. It has been shown that painful stimulation is a more effective reinforcing agent than brain stimulation. Synchronous recordings pointed to a distinct correlation of activity in some structures (field CA1 of the hippocampus) with that of the visual cortex, while in others the EP form characteristically changed at different stages of learning (thalamic reticular nucleus), and in still others, there were no EP changes (midbrain reticular formation) at any stage of learning.     

Interaction of reticular structures in the brain of the cat

In acute and chronic experiments on 35 cats an inhibitory influence was found of the caudal reticular nucleus of pons Varolii on unit activity of the sensorimotor cortex and dorsal part of the midbrain reticular formation. The influence of this structure on unit activity of the ventral part of the midbrain reticular formation was mainly of a facilitatory character. Activation of the ventral part inhibited the unit activity of the dorsal part of the same structure. Consequently, the caudal reticular nucleus of pons Varolii elicits inhibition at the level not only of the cerebral cortex but also of the midbrain reticular formation (of its dorsal part). The character of these influences coincides with that of unit activity changes of these two areas of the midbrain reticular formation during the development of the paradoxical phase of sleep. The obtained facts must underlie the stopping of convulsive activity in this phase of sleep.     

Expression, microsomal and mitochondrial activities of cytochrome P450 enzymes in brain regions from control and phenobarbital-treated rabbits

Expression and monooxygenase activity of various cytochrome P450 (CYP) enzymes along with constitutive androstane (CAR) and the pregnane X (PXR) receptors were investigated in the brain of control and phenobarbital-treated rabbits (80 mg/kg for 4 days). RT-PCR analysis, using specific primers, demonstrated that in control rabbits mRNAs of CYP 2A10, 2B4/5 and 3A6 were expressed, though to a different extent, in the liver, as well as in brain cortex, midbrain, cerebellum, striatum, hippocampus and hypothalamus, whilst CYP2A11 and 4B1 were not expressed in the hypothalamus. CAR was expressed in liver and all the brain regions examined, whereas the PXR was expressed only in liver and cortex. Real time RT-PCR analysis demonstrated that in vivo treatment with phenobarbital, in contrast with what happened in liver, did not induce the expression of CYP 2B4/5 mRNA in cortex, midbrain and cerebellum. NADPH cytochrome c reductase and some other enzymatic activities markers of CYP 2A, 2B, 3A and 4B activities were studied in liver microsomes as well as in microsomes and mitochondria of brain cortex, midbrain and cerebellum of control and phenobarbital-treated rabbits. In contrast to what was observed in liver, phenobarbital treatment did not induce the aforementioned monooxygenase activities in brain. However, we cannot exclude that a longer phenobarbital treatment may lead to a significant induction of CYP activities in brain. These findings indicated that brain CYPs, despite the presence of CAR, were resistant to phenobarbital induction, indicating a possible different regulation of these enzymes between brain and liver.     

Electroencephalographic effects of the intracentral administration of antibodies to brain-specific antigen S-100]

The EEG method with the assessment of the rhythm power on analogue computers was used to examine the effects of intracentral administration of antibodies to the brain-specific antigen S-100 (S-100 protein). Intracerebral injections of antibodies to S-100 protein caused an increase of the EEG basic rhythm power in the hippocampus, caudate nucleus and the mesenphalic reticular formation, with the subsequent development of epileptiform activity in these structures.     

Dynamics of brain rhythmic and evoked potentials

In this study, the simultaneously recorded and selectively averaged evoked potentials in some of the structures of the auditory pathway (acoustical cortex, medial geniculate nucleus, inferior colliculus), in the reticular formation and the hippocampus of the cat during sleep as well as the simultaneous amplitude frequency characteristics of these structures are given. The power spectral density functions computed from the simultaneously recorded spontaneous activities of these structures are also presented. Using these results, the following analyses are accomplished:(1) determination of the dynamics of potentials simultaneously obtained from various structures, in order to evaluate the common features of their system characteristics; (2) determination of the relationship (or interactions) between rhythmic activity and evoked potentials of the brain.     

Commissural channels of visual information transmission

Experiments were made in adult cats with different transections of the classical and commissural visual tracts to study evoked potentials and unit neuronal activity in response to visual stimulation. The commissural channels of the telencephalon, diencephalon and mesencephalon were demonstrated to be highly effective in visual information conduction to the visual cortex. Complete transection of the classical and commissural tracts with the exception of the commissural tract of the third ventricle fundus and midbrain reticular formation resulted in the disappearance of evoked potentials in the visual cortex in response to light flashes, despite the fact that 8 of the 15 recorded neurons responded to photostimulation. Activation of such neurons was caused by visual information conduction via two possible commissural channels: midbrain reticular formation and subventricular interhemispheric commissures of the diencephalon.     

Intercentral reticulo-cortical relations of brain electrical activity during "animal hypnosis" in rabbits

The electrical activity of the right and left sensorimotor and premotor cortical areas and right and left medulary reticular formation was recorded during "animal hypnosis" in rabbits. In this state, the spectral power of potentials (predominantly, in the delta-range) recorded from the left reticular formation was higher than that recorded from the right side. The value of the function of coherence between the right and left reticular recordings was decreased to 0.1-0.2 in the whole frequency range. The tight-side intrahemispheric coherence between the activities recorded from the sensorimotor cortex and reticular formation was higher than respective left-side values, whereas the coherent relations between the activities recorded from the reticular formation and premotor cortex were not changed (as compared to nonhypnotic state).     

An analysis of the neuronal processes in the activating brain systems of the rat during the acquisition of an instrumental defense reflex

In chronic experiment, a defensive conditioned reflex was elaborated in rats with electrodes implanted in the reticular oral pons nucleus, cortico-medial group of amygdalar nuclei, ventromedial hypothalamic nucleus and central grey substance of the midbrain. Synchronization of the activity of neuronal groups of emotiogenic formations in the studied brain structures, became enhanced at formation of the conditioned reflex. A dependence was revealed of the level of correlation of limbic neuronal groups activity on functional state of the reticular formation, as well as neurochemical correlation mechanisms. The increase (decrease) of coefficients of correlation of the activity of neuronal ensembles of limbic structures was accompanied by a change of evoked potentials parameters recorded in them.     

The effect of arginine vasopressin on the excitability and fatty acid content of the brain structures in rats with a neurosis

Experiments on rats with chronic bipolar electrodes implanted into the frontal cortex (FC), dorsal hippocampus (DH) and midbrain reticular formation (RF) established that the neurotic state (model "conflict of afferent excitation") was characterised by the increase in structure excitability: FC--15.4% (P less than 0.01), DH--12.4% (P = 0.05) and RF--17.5% (P less than 0.001). The presence of free fatty acids (FFA) revealed by chromatograph Schimadzu in brain cortex (BC), hippocampus (H) and midbrain (MB) in acute experiments evidenced the increase in the level of linolinic acid in all matters within the limits of 64-162% (P less than 0.05) and also different changes in arachidonic acid in BC and subcortical structures. The level of arachidonic acid increased by 120% (P less than 0.01) in BC but it decreased in H and MB within the limits of 34-56%. AVP (1 micrograms/kg) decreased excitability of FC by 6% (P less than 0.001), of H--by 8% (P less than 0.01) and RF--by 6%. In this case FFA, especially arachidonic acid, was increased in H and MB (by 2.5-6 times). The quantity of palmitic, stearic and oleic acids increased.     

The cross-correlation relations of the electrical activity of the cortical structures at different levels of the activation of the midbrain reticular formation in the rabbit]

Changes of correlation coefficients and coherence of the delta-, theta- and alpha-rhythms were studied between the somatosensory, motor and visual neocortex areas, dorsal hippocampus and dentate fascia at stimulation frequencies of the midbrain reticular formation from 60 to 1000 imp/s. It was shown that correlation coefficient between the structures studied increased at 60-200 imp/s and decreased at the further increase of stimulation frequency. In pairs with the visual area the correlation coefficient changed but little. The delta-rhythms coherence tended to decrease with the increase of stimulation frequency. Coherence of the theta-rhythms between the neocortical areas and the hippocampus increased with the increase of stimulation frequency up to 200 imp/s and decreased at higher frequency stimulation while in pairs of these areas with the dentate fascia it continued to rise with the increase of stimulation frequency up to 1000 imp/s. The coherence of the alpha-rhythms was almost unchanged at 60-200 imp/s and mostly had an increase at higher frequency stimulation.     

Dependence of the spectrum of electrical activity of the neocortex and hippocampus in rabbits on the intensity of the stimulation of the midbrain reticular formation

Study of dominating spectral maxima in delta-, theta- and alpha-ranges of the electrical activity of rabbits' neocortex and hippocampus showed that an increase of the frequency of the mesencephalic reticular formation stimulation from 60 to 200 imp/s led in both structures to an enhancement of the theta-rhythm (up to 130% in the neocortex and 147% in the hippocampus) and suppression of delta- and alpha-activity (correspondingly up to 67 and 34% in the neocortex and 37 and 48% in the hippocampus) with subsequent weakening of this effect at frequency increase up to 1000 imp/s. In the hippocampus, the reticular stimulation was more effective with respect to the theta- and delta-rhythms, and in the neocortex--with respect to the alpha-rhythm. In both structures the theta-rhythm amplitude changed less than the amplitude of the delta- and alpha-activities. Dependence of the amplitude of dominating rhythms on intensity of reticular formation stimulation differed from the analogous frequency dependence of the same rhythms.     

Toxicological consequences of differential regulation of cytochrome p450 isoforms in rat brain regions by phenobarbital

Cytochrome P4502B is an isoform of cytochrome P450 (P450) that is induced by the anticonvulsant drug phenobarbital. Here, we demonstrate the constitutive expression and predominant localization of CYP2B in neurons of rat brain. Administration of phenobarbital to rats resulted in selective induction of P450 levels in cortex and midbrain, while other regions were unaffected. Immunohistochemical localization of P4502B in brains of phenobarbital treated rats revealed localization of P4502B in neuronal cells, most predominantly the reticular neurons in midbrain. The anticancer agent 9-methoxy-N(2)-methylellipticinium acetate (MMEA) has been shown to exhibit preferential neuronal toxicity in vitro. Pretreatment of rats with phenobarbital potentiated the toxicity of intrathecally administered MMEA in vivo, as seen by the degeneration of reticular neurons. Thus, induction of P450 in selective regions of brain by phenobarbital would profoundly influence xenobiotic metabolism in these regions, especially in clinical situations where phenobarbital is coadministered with other psychoactive drugs/xenobiotics.     

Role of the reticular formation of the midbrain in the process of formation of background activity of cortex neurons

In strict experimental conditions the basic activity of optic-cortex neurons in the rabbit was depressed after transverse section at the level of the rostral part of the reticular formation of the midbrain. Electrolytic destruction or functional blockage of the midbrain reticular formation (nucleus reticularis tegmenti) produces a decrease in frequency and magnitude in the grouping indexes of the cortex-neuron pulses that manifest the activity in these conditions. Destruction of specific nuclei in the optic pathway (those of the lateral geniculate body and the corpora bigemina) made no substantial change in the nature of the cortex-neuron pulses. Comparison of the parameters of pulsation activity of the same cortex neurons, as recorded before and after functional exclusion of the midbrain reticular formation, revealed that the increase in grouping of these pulses after the reticular formation was blocked induced changes in the intervals between groups of pulses, while the frequency of pulses within the groups remained constant. On the basis of the data obtained we may assume that the midbrain reticular formation plays an important role in generation of the background activity of cortex neurons, being a triggering mechanism that sets off a group of pulses. Distribution of pulses within the group is apparently due to the activity of cortex mechanisms only.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 43–51, January–February, 1970.     

Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.     

Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation

Long-term potentiation in the hippocampus can be enhanced and prolonged by dopaminergic inputs from midbrain structures such as the substantia nigra. This improved synaptic plasticity is hypothesized to be associated with better memory consolidation in the hippocampus. We used a condition that reliably elicits a dopaminergic response, reward anticipation, to study the relationship between activity of dopaminergic midbrain areas and hippocampal long-term memory in healthy adults. Pictures of object drawings that predicted monetary reward were associated with stronger fMRI activity in reward-related brain areas, including the substantia nigra, compared with non-reward-predicting pictures. Three weeks later, recollection and source memory were better for reward-predicting than for non-reward-predicting pictures. FMRI activity in the hippocampus and the midbrain was higher for reward-predicting pictures that were later recognized compared with later forgotten pictures. These data are consistent with the hypothesis that activation of dopaminergic midbrain regions enhances hippocampus-dependent memory formation, possibly by enhancing consolidation.