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.     

Effect of deafferentation of the lateral geniculate body on its background activity

Elimination of reticular inputs to the lateral geniculate body (LGB) by sectioning of one half of the midbrain operculum, did not affect significantly the characteristics of the LGB evoked potential to light stimulus. At the same time LGB response to stimulation of the reticular formation by a single current impulse, though did not disappear completely, but changed greatly: its latency became twice as long, the negative component of the response was no more recorded. In conditions of LGB deafferentation, the characteristics of all rhythms of its electrical activity, besides the alpha-like one, considerably changed. At the same time, exactly this last rhythm underwent the greatest changes on the EEG of the visual cortex. On the basis of the obtained data it is suggested that the reticular formation takes a considerable and multiple part in generation of LGB rhythmic activity and that changes in its characteristics are clearly reflected in the ECoG rhythms formation. Retention of the LGB visual evoked potential and of the response to stimulation of the reticular formation after the section of one half of the midbrain operculum testifies to the presence of several reticular inputs to LGB.     

Influence of cholinergic and adrenergic agents of the electric activity of the brain and the heart under hypoxia

Injection of adrenergic and cholinergic agents to animals in the normal athmospheric conditions did not tigger drastic changes on the electric activity of the brain and heart. Acutehipoxia demands high adaptability from the body. In such conditions stimulation of reticular formation and hypothalamus produces different changes in the EEG and ECG activity whith injecting adrenergic and cholinergic agents. It was determined that cholinergic influence are effective in the regulation of electrical brain activity while adrenergics are more important for the realization of descending influences of the truncus cerebri vegetative centers and are less active in the modulation of the cerebral cortex activity.     

Substance P in the central mechanism of the rabbit feeding response evoked by stimulation of the lateral hypothalamus

The effects of substance P on the central mechanisms of food motivation elicited by electrical stimulation of the lateral hypothalamus were studied in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) brought about a dramatic reduction in the excitability of the "food center" in the hypothalamus, which returned to normal 45-60 minutes after injection. Higher concentrations of substance P provoked food behavior inversion up to the replacement of food motivation by avoidance behavior. Intravenous injections of substance P disturbed the relationships between the hippocamp, midbrain reticular formation and hypothalamus seen in health. This manifested in complete cessation of the inhibitory effects of the dorsal hippocamp and facilitating influences of the midbrain reticular formation on the excitability of the hypothalamic "food center". It is assumed that disorders of the central mechanisms of food motivation may arise from the effects produced by substance P directly on the central nervous system or on the brain via changes in the hormonal balance and responses of the autonomous nervous system.     

Evoked potentials in the reticular formation of the rabbit midbrain during formation of a dominant focus in it

During creation of a dominant focus in the midbrain reticular formation (RF) by its multiple stimulation with a high-frequency current (stimulation frequency 200 Hz, pulse duration 0.1-0.5 ms, voltage 1-3 V, duration 5 s) a statistically significant increase of the amplitude of the evoked potential (EP) in RF to light flashes was revealed in comparison with background data. Significant increase of EP amplitude was also observed in RF in response to the same stimuli applied in successive experiments without RF stimulation, which pointed to the existence of a latent dominant focus in the CNS.     

Functional changes in neurosecretory cells of the anterior hypothalamic nuclei after stimulation of the midbrain reticular formation

The functional activity of the neurosecretory cells in the supraoptic and paraventricular nuclei was studied in male Wistar albino rats at various intervals after electric stimulation of the midbrain reticular formation. These studies showed that such stimulation elicits higher functional activity of the neurosecretory cells in the anterior hypothalamic nuclei, characterized by increased secretory synthesis by these cells and rapid transport of the neurosecretion. These changes were most pronounced 1 h after stimulation of the reticular formation. The changes observed were unidirectional in both neurosecretory centers, but their manifestation was different: in the supraoptic nucleus the reaction was more intense but short lived, in the paraventricular it was less intense but lasted longer.A. A. Bogomolets Institute of Physiology, Academy of Sciences, Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 394–400, July–August, 1971.     

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.     

Reticular unit responses in rats during functional blocking of cortical representation of the stimulated paw

Responses of single reticular units to electrodermal stimulation were studied in unanesthetized, immobilized rats during cold blocking of the cortical representation of the stimulated limbs. Local cooling of the somatosensory cortex caused reversible and opposite changes in responses of 60 of the 86 neurons tested. In 25 cells responses only to stimulation of the limb whose sensory projection was in the cooled zone were modified. In 31 neurons changes in responses to this stimulation predominated and in 22 they were comparable with changes in responses of the same neurons to electrodermal stimulation of the other limb, whose cortical representation was intact. Cold blocking of the cortical response to presentation of one of the stimuli thus modifies the conditions for information processing in the neuron net of the reticular formation selectively for the response to presentation of that same stimulus.I. M. Sechenov Institute of Evolutionary Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 13, No. 2, pp. 179–186, March–April, 1981.     

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.     

Characteristics of cortical responses to electrostimulation of the internal geniculate body during formation of a defensive conditioned reflex]

During elaboration of a classical defensive conditioned reflex the dogs exhibited a dependence of the changes in amplitude and configuration of evoked potentials (EP) to electrical stimulation of the medial geniculate body (MGB), a conditioned stimulus, on the nature of effector manifestation of the conditioned reflex: the late components were the most depressed at multiple phasic reactions and not infrequently increased and became complicated at single and short motor reactions as well as at their incidental absence. The primary oscillations, while mostly remaining unchanged, were depressed in the case of conditioned reactions attended with a general motor restlessness. A difference has been revealed during conditioning in the EP changes to electrical stimulation of MGB and to an adequate peripheral stimulation. It has been assumed that EP changes during conditioned activity are determined by the relationship between the levels of tonic and phasic cortical activation.     

Tonic facilitatory influences of dorsal pontine reticular structures on the response gain of limb extensors to sinusoidal labyrinth and neck stimulations

Experiments were performed to find out whether changes in resting discharge of the inhibitory reticulospinal (RS) neurons of the medulla, produced either by selective destruction or by cholinergic activation of a pontine tegmental reticular system, may modify the response gain of limb extensor muscles to given parameters of roll tilt of the animal or neck rotation. In precollicular decerebrate cats, an electrolytic lesion of the dorsal aspect of the pontine tegmentum, which slightly increased the tonic contraction of limb extensors, greatly decreased the amplitude of the multiunit EMG response of forelimb extensor muscles, i.e. of the medial head of the triceps brachii, to roll tilt of the animal and neck rotation (at 0.15 Hz, +/- 10 degrees), leading to selective stimulation of labyrinth or neck receptors. Correspondingly, the response gain of the forelimb extensors to labyrinth and neck stimulation decreased, but no change in the phase angle of the responses was observed. These findings did not depend on the increased postural activity, since they were still observed in the absence of any change in spontaneous EMG activity of the triceps brachii following the lesion. The changes in posture as well as in response gain of the forelimb extensors to labyrinth and neck stimulation produced by the pontine lesion appeared suddenly, and persisted for several hours throughout the survival period. Moreover, these changes involved mainly, but not exclusively, the limbs ipsilateral to the side of the lesion. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the dorsal aspect of the pontine tegmentum located immediately ventral to the locus coeruleus (LC); this area corresponded to the peri-LC region as well as the surrounding pontine reticular formation (RF), including the dorsal aspect of the central tegmental field. This region closely corresponds to the area from which a tegmentoreticular tract, ending on the medullary inhibitory area, originates. It was previously shown that unilateral or bilateral lesion of the LC, which decreased the extensor tonus in the ipsilateral limbs, greatly enhanced the response gain of the triceps brachii to sinusoidal stimulation of labyrinth and neck receptors. These findings were attributed to suppression of an inhibitory influence that the LC exerts on the dorsal pontine reticular structures described above.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of microinjection of a cholinergic agonist into the locus coeruleus on the gain of vestibulospinal reflexes in decerebrate cats

1. Experiments were performed in precollicular decerebrate cats to determine whether activation of locus coeruleus (LC) neurons elicited by local injection of the cholinergic agonist carbachol modifies the dynamic characteristics of responses of forelimb extensors to selective stimulation of labyrinth receptors resulting from roll tilt of the animal. 2. Injection of 0.1-0.4 microliter (usually 0.25 microliter) of carbachol at a concentration of 0.02-0.1 micrograms/microliter of sterile saline into the LC of one side, which slightly increased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly decreased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of this forelimb extensor decreased. Moreover, a significant increase in phase lag of the responses was observed. These findings did not result from the increased postural activity, since they were still observed when the limb position was adjusted so that the spontaneous EMG activity remained constant throughout the experiments. 3. The changes in posture as well as in response characteristics of the forelimb extensor to labyrinth stimulation produced by carbachol injection appeared a few min after the injection and soon reached a plateau level which persisted for several hours before returning to the control levels. 4. The effects described above involved mainly, if not exclusively, the limbs ipsilateral to the side of the injection. However, the effects of local injection into the LC of one side could be reproduced on the contralateral side following injection into the LC of that side. 5. The increase in phase lag of the multiunit EMG responses of the triceps brachii to labyrinth stimulation appeared at a threshold lower than that required to decrease the response gain of this extensor muscle. These findings suggest that different neuronal populations within the LC complex, one projecting directly to the spinal cord, the other projecting indirectly through the pontine reticular formation, are involved in the control of phase angle and gain of the vestibulospinal reflexes, respectively. However, as soon as the threshold was reached the effects described above were dose-dependent. 6. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the LC. In fact, postural and reflex changes opposite in sign to those described above were obtained when the same amount of carbachol was injected into the dorsal aspect of the pontine reticular formation (pRF) located immediately ventral to the LC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanisms for the Intracellular Manipulation of Organelles by Conventional Electroporation

Conventional electroporation (EP) changes both the conductance and molecular permeability of the plasma membrane (PM) of cells and is a standard method for delivering both biologically active and probe molecules of a wide range of sizes into cells. However, the underlying mechanisms at the molecular and cellular levels remain controversial. Here we introduce a mathematical cell model that contains representative organelles (nucleus, endoplasmic reticulum, mitochondria) and includes a dynamic EP model, which describes formation, expansion, contraction, and destruction for the plasma and all organelle membranes. We show that conventional EP provides transient electrical pathways into the cell, sufficient to create significant intracellular fields. This emerging intracellular electrical field is a secondary effect due to EP and can cause transmembrane voltages at the organelles, which are large enough and long enough to gate organelle channels, and even sufficient, at some field strengths, for the poration of organelle membranes. This suggests an alternative to nanosecond pulsed electric fields for intracellular manipulations.     

Involvement of mesencephalic reticular formation neurons in cat conditioned reflexes

Traditional defensive and operant food reflexes were used to investigate neuronal responses of the mesencephalic reticular formation. It was found that these neurons may be divided into different groups according to function, depending on how they respond to positive conditioning stimuli. Of the two main groups of neurons with sustained tonic reactions one is activated in response to positive acoustic conditioning stimulation; it no longer reacts to the same stimulus after extinction of the reflex, while the other only becomes involved in response to positive stimulation accompanying the initiation of movement. Neurons belonging to the second group begin to respond directly to acoustic stimulation after extinction of the conditioned reflex. Neurons of the mesencephalic reticular formation can thus exercise additional tonic ascending effects both in the production and inner inhibition of the conditioned reflex. The group of neurons with a phasic reaction, i.e., a double response (a direct response to sound and another produced by movement) displayed a drop in spontaneous activity during the shaping of inhibition of differentiation and of extinction in particular. It was found that the initial changes in the spike response of reticular formation neurons during conditioning and pseudo-conditioning are similar. There are thus grounds for stating that neurons of the mesencephalic reticular formation participate in the shaping, production, and inner inhibition of traditional and operant conditioned reflexes in a differentiated capacity rather than as a population reacting identically.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 161–171, March–April, 1986.     

Limbico-reticular relations during formation of various motivation responses in rabbits subjected to ethanol administration

Chronic experiments on rabbits with electrodes implanted into different limbic-midbrain structures were made to study the effects of a single intravenous injection of ethanol (0.5 g/kg) on the background EEG during formation of food motivation and avoidance behavior from the criterion of the power of the main EEG rhythms. Intravenous injection of ethanol resulted in an increase in the power of beta-, alpha- and theta-rhythms in the frontal cortex, and in that of alpha- and theta-rhythms in the occipital area of the neocortex. New patterns of the powers of the main EEG rhythms recorded in animals exposed to ethanol during electric stimulation of the lateral and ventromedial hypothalamus, evoking food motivation and avoidance behavior, as well as during electrical stimulation of the dorsal hippocamp and mesencephalic reticular formation that correlate with changes in the functions of the study limbic-mesencephalic structures attest to profound ethanol-induced abnormalities of the central mechanisms of food motivation and avoidance behavior.     

Time and Frequency-Dependent Modulation of Local Field Potential Synchronization by Deep Brain Stimulation

High-frequency electrical stimulation of specific brain structures, known as deep brain stimulation (DBS), is an effective treatment for movement disorders, but mechanisms of action remain unclear. We examined the time-dependent effects of DBS applied to the entopeduncular nucleus (EP), the rat homolog of the internal globus pallidus, a target used for treatment of both dystonia and Parkinson’s disease (PD). We performed simultaneous multi-site local field potential (LFP) recordings in urethane-anesthetized rats to assess the effects of high-frequency (HF, 130 Hz; clinically effective), low-frequency (LF, 15 Hz; ineffective) and sham DBS delivered to EP. LFP activity was recorded from dorsal striatum (STR), ventroanterior thalamus (VA), primary motor cortex (M1), and the stimulation site in EP. Spontaneous and acute stimulation-induced LFP oscillation power and functional connectivity were assessed at baseline, and after 30, 60, and 90 minutes of stimulation. HF EP DBS produced widespread alterations in spontaneous and stimulus-induced LFP oscillations, with some effects similar across regions and others occurring in a region- and frequency band-specific manner. Many of these changes evolved over time. HF EP DBS produced an initial transient reduction in power in the low beta band in M1 and STR; however, phase synchronization between these regions in the low beta band was markedly suppressed at all time points. DBS also enhanced low gamma synchronization throughout the circuit. With sustained stimulation, there were significant reductions in low beta synchronization between M1-VA and STR-VA, and increases in power within regions in the faster frequency bands. HF DBS also suppressed the ability of acute EP stimulation to induce beta oscillations in all regions along the circuit. This dynamic pattern of synchronizing and desynchronizing effects of EP DBS suggests a complex modulation of activity along cortico-BG-thalamic circuits underlying the therapeutic effects of GPi DBS for conditions such as PD and dystonia.     

Evoked frequency stabilization in the electrical activity of the cat brain

In this study, our previous results on the important relation between EEG and EPs were extended by experiments with chronically implanted and freely moving cats, which had electrodes at the acoustical cortex, inferior colliculus and reticular formation. During the experiments the frequency stabilization upon sound stimulation was shown in the frequency domain by comparison of the pre-stimulus power spectra and post-stimulus amplitude frequency characteristics. Comparative frequency domain analysis of about 75 EEG-EPograms (sample of spontaneous activities just prior to stimulation and single evoked potentials following the stimulation), which were recorded from all the brain nuclei mentioned above and from each of the 11 cats, was performed as follows: 1) Power spectra of the EEG-records prior to stimulus were evaluated. 2) Instantaneous frequency characteristics of single EPs were obtained by the Fourier transform. 3) Distribution of the amplitude maxima of the EP-frequency characteristics and the distribution of the EEG-spectral peaks were compared by plotting two types of histograms containing relevant spectral peaks before and after the stimulation. In a frequency range between 1–1000 Hz, the frequency distribution of the EP records from RF and IC were accumulated in narrow discrete frequency channels, whereas, the distribution of the spectral peaks of the EEG depicted frequency spread in broad channels. The frequency stabilization of the EP records from GEA, in the alpha frequency range, was also observed. This effect was described by a factor which we called as the Frequency Stabilization Factor. The results presented in this study showed that the frequency stabilization of the brain's electrical activity induced by sensory stimulation displayed a fluctuation leading to frequency stabilization factors between 0.95 and 5.00. The frequency stabilization and relevant power enhancement upon stimulation strongly support our contention that evoked potential results from the frequency stabilization of the spontaneous activity, triggered by stimulation.Supported by Grant No. TAG-345 of the Scientific and Technical Research Council of Turkey     

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.     

Effects of bulbar stimulation on smooth muscle tone in the feline airway

Changes induced in tracheal smooth muscle tone by bulbar electrical stimulation were investigated in 30 cats anesthetized with a chloralose-urethane mixture and paralyzed with succinyl choline bromide. Raised tonus was mainly observed during stimulation of the caudal section of the dorsal motor nucleus of the vagus nerve, the vicinity of the nucleus ambiguus, and the adjoining reticular formation structures. Attenuation, however, was produced by stimulating bulbar reticular formation nuclei at a level 1 mm caudal and 6 mm rostral to the obex. Raised tonus is thought to be connected with activation of efferent neurons belonging to the motor nucleus of the vagal nerve, as well as axons of nucleus ambiguus neurons in transit through the medial zone, whilst attenuation is connected with excitation of sympathotonic reticular neurons, inhibitory neurons activated by pulmonary stretch receptors, and possibly with vagal efferent neurons activating the non-adrenergic inhibitory nervous system of the bronchi.Medical Institute, Latvian Ministry of Health, Riga. Cardiology Research Institute. Latvian Ministry of Health, Riga. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 320–326, May–June, 1989.     

Interaction between unit responses of the cat cerebellar cortex during paired stimulation of the forelimbs

Interaction between spike responses of 41 cerebellar cortical neurons to electrical stimulation of the two forelimbs with different intervals between stimuli were studied in cats anesthetized with chloralose and pentobarbital. The responsiveness of neurons with a phasic type of discharge to testing stimulation of the limb was reduced for 300–500 msec or longer after conditioning stimulation of the other limb. Interaction between the responses was less clear in neurons with a tonic type of response. Interaction was absent or was summating in character if the stimuli were applied at the same times. Only if the intertrial intervals were 50–150 msec was regular inhibition of the responses of tonic type to the testing stimulus observed. It is postulated that the nucleus of the inferior olive participates in the interaction between phasic unit responses during simultaneous stimulation of the two limbs or to stimulation separated by short intervals (under 30 msec). With longer intervals between stimuli, interaction between responses of either type is connected with involvement of the lateral reticular nucleus. In the process of interaction competitive relations may develop between responses caused by impulses reaching neurons of the cerebellar cortex along climbing and mossy fibers.