Long-term action of camphor on "audio-sensitive" rats: Electrophysiological study and mathematical modeling of properties of neuronal networks

Krushinskii-Molodkina (KM) strain rats genetically predisposed to audiogenic convulsive reaction were given repeated camphor injections in gradually increasing doses (starting at the minimum threshold level required for seizures to occur) over a 4–5 month period. Animals were able to tolerate camphor at doses 3/2–3 times convulsion threshold level without seizure occurring once habituation to the action of this convulsant had been developed. At the same time, the cortical motor zone of strain KM rats acquired properties typical of an epileptic focus: spontaneous epileptiform firing peaks were noted in the background electrical activity of this zone. A decline in the parameter reflecting efficacy of the mechanisms underlying recurrent inhibition emerged in the cortical motor zone of strain KM rats receiving camphor from calculating the parameters of neuronal network from spectra of summated potentials (using the model of a neuronal network). It is suggested that the development of compensatory processes making it possible to avoid generalized seizure following administration of camphor in large doses is associated with intensification of inhibitory caudate function and attenuated hippocampal excitation.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 193–200, March–April, 1990.     

Spectral analysis of EEG in normal rats and in rats genetically predisposed to seizures

Spectral and visual analyses were performed on the EEG of the motor and visual cortex, hippocampus, caudate nucleus, and intralaminary thalamic nuclei in two strains of rats; animals were maintained in a state of "awake immobility." It was found that KM rats, genetically predisposed to audiogenic fits, differed from the Wistar strain not subject to this genetic predisposition in that mean relative intensity of theta rhythm diminished and high amplitude slow irregular hippocampal activity intensified in the neocortex, as did generalized spindling. Susceptibility to seizure was reduced in KM rats as a result of protracted and graded increasing camphor administration to match the level of mean EEG spectral density changes characteristic of the Wistar strain. The part which brainstem reticular formation mechanisms may play in raising susceptibility to seizures is discussed, together with the EEG pattern characteristic of this condition.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 171–179, March–April, 1987.     

Effects of Deprivation of the Quick-Wave Sleep in Rats with Inherited Predisposition to Audiogenic Convulsions

In experiments on rats of Krushinskii–Molodkina line (KM) with genetic predisposition to audiogenic convulsions, effects of the 3- and 6-h periods of the absence of the quick-wave sleep (QS) were studied in animals under natural conditions as well as of selective deprivations of QS on EEG spectral characteristics in the wakening–sleep cycle, on organization of the cycle, and on intensity of convulsive symptoms. The QS deprivation for 3, 6, 9, and 12 h was produced by the classic methods of small platforms or of soft awakening. The data are presented about changes of the cycle parameters in the course of natural and experimental deprivations as well as about the dynamics of restoration of the cycle structure for 12 h of the post-deprivation period. It was established that during and after the QS deprivations (by any duration), in EEG of the hippocampus, caudate nucleus, medial central nucleus of thalamus, somato-sensory, visual and auditory cortex of the KM rat brain, no appearance of the paroxysmal fires was revealed in any of the states of the wakening–sleep cycle. It was also found that the selective QS deprivation did not affect duration of the latent period and parameters of the generalized tonic-clonic audiogenic convulsions. It is stated that in rats of the KM line that have the hidden convulsive syndrome, the used kinds and methods of QS deprivation fail to activate the epileptiform manifestations.     

Calculation of parameters of neuronal network model on the basis of analysis of power spectra of rat brain biopotentials

On the basis of neuronal network a linearized model of power spectrum of the network stable activity was calculated with the approximation of external input by "white" noise. The power spectrum function obtained was used for approximation of the power spectra of the rats motor cortex potentials by the least squares method. As a result the network parameters modelling excitatory and inhibitory cellular and synaptic mechanisms were calculated for two rat strains differing in seizure readiness. As a result of calculations genetically predisposed to seizures KM rats were assumed to differ from unpredisposed to seizures Wistar rats in the increase of efficacy of neuronal interactions (excitatory and inhibitory) as a consequence of the enhanced neuronal "reactivity".     

Spectral and coherence EEG analysis of rats differing in the level of seizure readiness

The resting EEGs of several brain structures (motor and visual cortex, caudate nucleus and intralaminar thalamic nuclei) were submitted to spectral and coherence computer analyses in two rat strains. Genetically predisposed to convulsive state KM rats were shown to differ from nonpredisposed Wistar rats in EEG spectral properties. KM rats EEG pattern was characterized by increase of low frequencies (1-2 Hz) power and decrease of faster activity (5-12 Hz) power in cortical spectrograms as well as by decrease of caudate nucleus EEG absolute power. The coherence value between cortical or subcortical structures at below 4 Hz was intensified in KM rats. Reinforcement of cortical auto-oscillating properties manifested by ECoG synchronization in cortical-thalamic resonance interaction as well as weakening of striatal inhibitory system may constitute neurophysiological mechanisms of enhanced convulsive readiness. The probable role of mediator imbalance in these mechanisms is discussed.     

Laboratory rat selection for the trait “the absence of audiogenic seizure proneness”

The hybrids between Krushinsky-Molodkina (KM) inbred strain, selected for high predisposition to audiogenic epilepsy (AE), and Wistar rats non-prone to audiogenic seizure were the initial population for selection. Rats were selected for the trait ??the absence of audiogenic seizure proneness??. The creation of such strain in which the significant proportion of animals develop no AE in response to sound and share partly the genetic background of the KM strain is very important for the correct use of KM strain as the laboratory model of seizure states. As alleles which determine the AE proneness are recessive the selection for the ??opposite?? trait proceeds necessarily slow.     

Laboratory rat selection for the trait "the absence of audiogenic seizure proneness"

The hybrids between Krushinsky-Molodkina (KM) inbred strain, selected for high predisposition to audiogenic epilepsy (AE), and Wistar rats non-prone to audiogenic seizure were the initial population for selection. Rats were selected for the trait "the absence of audiogenic seizure proneness". The creation of such strain in which the significant proportion of animals develop no AE in response to sound and share partly the genetic background of the KM strain is very important for the correct use of RV strain as the laboratory model of seizure states. As alleles which determine the AE proneness are recessive the selection for the "opposite" trait proceeds necessarily slow.     

The phenomenon of lowering a seizure readiness level after frequent audiogenic seizures in Krushinskiĭ-Molodkina rats

The spectral analysis of the EEG activity of several brain structures (somatosensory, visual and auditory areas of the cortex, hippocampus, caudate nucleus and central medial thalamic nucleus) in the wakefulness-sleep cycle in Krushinskii--Molodkina strain rats with inherited predisposition to audiogenic seizures using long-lastint reducing of the seizure readiness level revealed in these animals after frequentative audiogenic generalized tonicclonic seizures, was performed. The reducing susceptibility to convulsiogenic sound stimuli in rats correlated with a decrease of the theta-range' waves level and increase of the expression alpha-range waves in the EEG during wakefulness. Probable role of reorganized functions of ascending activating brain systems in origination of the long reduction of susceptibility to the sound after frequentative audiogenic convulsions in rats is discussed.     

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 1, 2005, pp. 82–88.Original Russian Text Copyright © 2005 by Vataev, Oganesyan.     

Synaptic processes produced in cat rubrospinal neurons by stimulating the cerebellar nucleus interprositus

The activity produced in red nucleus rubrospinal neurons by stimulating the cerebellar nucleus interpositus was investigated in cats anesthetized with nembutal. Analysis of field potentials together with summated and single EPSP following paired and frequency stimulation of this structure revealed facilitation at cerebello-rubral synapses. It was found that this facilitation was not mediated by changes in presynaptic volleys. It is suggested that modification of the effectiveness of transmission is determined by characteristic features of the operation of cerebellar synapses on red nucleus neurons.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 630–636, September–October, 1987.     

Various forms of potentials recorded from caudate nucleus neurons

Spontaneous and evoked activity of caudate nucleus neurons was recorded extracellularly in acute experiments on cats. Different forms of potentials were found by analysis of the results. The potentials recorded belong to three types: ordinary action potentials; prepotentials or incomplete spikes differing from ordinary action potentials in their lower amplitude and slower decline, and complex discharges in which a spike of somewhat reduced amplitude is followed by a slow positive-negative wave. In the spontaneous activity prepotentials were observed both in complete action potentials and in isolation. The frequency of the complex discharges was 0.5–1 per second. The slow wave of these discharges blocked prepotential and action potential formation. The origin of these forms of potentials in neurons of the caudate nucleus is discussed and they are compared with analogous forms of potentials described for the Purkinje cells of the cerebellum.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukranian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 2, pp. 149–156, March–April, 1977.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectre electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of δ-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of α-and β₁-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.     

Involvement of visual specific and association cortex input in the shaping of neostriatal neuron response to visual stimulation in unanesthetized cats

During chronic experiments on unanesthetized cats neuronal response in the caudate nucleus to the presentation of local photic stimuli and electrical stimulation of the specific (field 17) and the association (Clare-Bishop) areas were compared. Stimulation of the Clare-Bishop area proved more effective than stimulating field 17 for neurons of the caudate nucleus; a response was produced in 47% of test neurons in comparison with 8% of units only in the specific area. Lower average values were observed for latency of neuronal response to stimulation of the Clare-Bishop area. An insignificant number of caudate nucleus neurons were activated as a result of stimulation of both cortical areas. A comparison between the response of one set of neurons to electrical cortical and visual stimulation showed that cells responding to visual stimulation were more highly activated by stimulating the Clare-Bishop area than by stimulation of field 17. This type of neuron predominated in the caudate nucleus. A discussion follows of the possible involvement of the Clare-Bishop area in shaping neuronal response to visual stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 619–627, September–October, 1985.     

Serotonin-induced changes in the action of functionally distinct neurons in Helix pomatia

The effects of serotonin on the amplitude of summated EPSP in interneurons and on the duration of action potentials in sensory neurons, interneurons, and motoneurons involved in avoidance behavior were investigated in functionally distinct neurons isolated from theHelix pomatia nervous system. The duration of action potentials in sensory neurons was found to increase under the effects of serotonin (and this could underly the rise in EPSP amplitude), although that of interneuron and motoneuron spikes did not change. The functional significance of selective neuronal response to a rise in serotonin concentration is discussed, together with the mechanics underlying such effects.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 316–322, May–June, 1987.     

Protracted depolarizing potentials of neurons in a strychninized cortical slab isolated from the cat

Neuronal response in a cortical slab isolated from the cat during surface application of strychnine was investigated in experiments on immobilized unanesthetized animals by means of intracellular recording techniques. Protracted depolarizing potentials (PDP) were found to occur spontaneously and in response to a single intracortical electrical stimulus in a proportion of the neurons. These potentials could be triggered by transformation of response along the lines of "paroxysmal depolarizing shift" (PDS) — hyperpolarization, with hyperpolarization replaced by depolarizing potentials. A further increase in depolarizing after-potentials resulted in the generation of PDP. These changes were normally accompanied by enhanced summated epileptiform activity in the isolated cortical slab. It is postulated that PDP were triggered by increased calcium conductance at the neuronal membrane during intensification of paroxysmal response in the isolated cortical slab.I. I. Mechnikov University, Odessa. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 19–23, January–February, 1990.     

Neurophysiological analysis of postnatal development of corticostriate connections in rabbits

Evoked potentials were recorded in the caudate nucleus of adult rabbits and young rabbits aged 2–30 days in response to stimulation of the ipsilateral motor cortex. The response of the caudate nucleus in the adult rabbit consisted of a positive-negative complex with latent period of 3–5 msec. Maximal amplitude of the response was observed in the dorsorostral region of the nucleus. As the recording electrode was inserted deeper, the amplitude of the response gradually decreased but without reversal of its polarity. Responses of the caudate nucleus to stimulation of the motor cortex were recorded as early as on the 3rd day after birth. These responses were indistinguishable in configuration from responses of the nucleus of adult rabbits. Their latent period was about 10 msec. Between the 16th and 20th day after birth the latent period of the response decreased considerably — from 9 to 5 msec, and by the 30th day of life it had reached its definitive value. With age the amplitude of the response increased but the threshold of stimulation decreased, The results indicate early functional maturation of connections of the motor cortex with the caudate nucleus and they agree with the results of morphological investigations of the structural development of the afferent systems of this nucleus.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 284–289, May–June, 1982.     

Modification of [3H]MK801 Binding to Rat Brain NMDA Receptors after the Administration of a Convulsant Drug and an Adenosine Analogue: A Quantitative Autoradiographic Study

Specific [³H]MK801 binding to rat brain NMDA receptors after the administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied by means of a quantitative autoradiographic method. MP administration (150 mg/kg, i.p.) caused significant decreases in [³H]MK801 binding in several hippocampus subareas and layers, mainly in CA1 and CA3 at seizure (11–27%) and postseizure (8–16%) and in cerebral occipital cortex at seizure (18–22%). In nucleus accumbens, a rise was observed at postseizure (44%) and a tendency to increase at seizure (24%). CPA (2mg/kg, i.p.) decreased ligand binding in hippocampus (CA1, CA2, CA3) (17–22%) and in occipital cerebral cortex (18–24%). When CPA was administered 30 minutes before MP (which delayed seizure onset) and rats were sacrified at seizure, decreases in [³H]MK801 binding in several layers of CA1 and CA3 of hippocampus (11–27%) and in CA1, CA2, CA3 (24–35%) after CPA+MP postseizure, and an increase in CA2 after CPA and CPA+MP postseizure (20–34%), were observed. A drop was found in the occipital subarea (18–24%) after CPA and in the frontal and occipital subarea after CPA+MP postseizure (24–34%) while no changes were observed in any treatment involving the other cerebral cortex regions, thalamic nuclei, caudate putamen and olfactory tubercle. These results show that [³H]MK801 binding changes according to drug treatment and the area being studied, thus indicating a different role in seizure activity.     

Ultrastructural correlates in pathology of nigrostriatal neurons after systemic MPTP administration in cats

Effects of a specific neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively affects dopaminergic structures, on the substantia nigra pars compacta, caudate nucleus, ventrolateral thalamic nucleus, hippocampus, and cerebellar cortex have been studied by electron microscopy in cats. Mass damage of the neuronal somata and axon terminals was observed only among the nigrostriatal neurons up to complete destruction in almost half of units. The majority of remaining neurons demonstrated a varying degree of dystrophic changes, mainly of the hydropic type. Submicroscopic characteristics of damaged nigral neurons indicated the disturbance of permeability of neuronal plasma membranes, disorders of the water-salt metabolism, suppression of mitochondrial functions, and disintegration of structural proteins, etc. However, signs of reparative processes together with destructive ones have been observed in part of the nigral neurons. The former may be indicative of the possibility of structural and functional restoration of intracellular organelles. Participation of the elements of the blood-brain barrier in the mechanism of general MPTP toxicity is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp 349–354, September–October, 1993.     

Efferent connections of the caudate nucleus in cats

Structural and ultrastructural changes in the frontal areas of the cortex and in the region of the globus pallidus were investigated after local and extensive destruction of the caudate nucleus. It was shown by the Fink-Heimer method that after local injury to the caudate nucleus by means of electrodes implanted 2–16 months before electrolytic destruction, only a few degenerating fibers of medium and thin caliber were present. Extensive destruction of the caudate nucleus (without preimplantation of electrodes) was followed by massive degeneration of fibers of different caliber in the frontal area of the cortex. After local injury to the caudate nucleus numerous thin degenerating axons 0.5–0.6 µ in diameter and degenerating terminals were found in the region of the globus pallidus. Degenerative changes in the axo-dendritic and axo-somatic terminals followed the "dark" type of course. It is concluded that no considerable direct projections of neurons of the caudate nucleus are present in the cortex. Degenerating fibers of average caliber in frontal areas of the cortex after destruction of the caudate nucleus are evidently axons of thalamic neurons and not from cells of the damaged nucleus.A. A. Bogomol'ets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 7, No. 2, pp. 165–171, March–April, 1975.