Experimental vestibulopathy produced as a result of formation of a generator of pathologically enhanced excitation in the vestibular nuclei (phenomenon of a determinative dispatch station)]

A possibility of formation of a generator of pathologically enhanced excitation in the system of the vestibular nuclei of the medulla oblongata by disturbance of their inhibitory processes (resulting in development of contralateral rotatory motions in animals) was shown. Experiments with electrical stimulation of the lateral vestibular nucleus and its coagulation showed the system of the vestibular neurons organizing the synchronous message by the vestibulo-spinal pathways to underlie the generator of the pathologically enhanced excitation. It was concluded that the generator of the pathologically enhanced excitation formed in the lateral vestibular nucleus as a result of disturbed inhibition underlied the hyperactive determinative dispatch station causing the syndrome of vestibulopathy     

Epileptiform activity in the somatosensory cortex of rats with trigeminal neuralgia]

It was shown in experiments on rats that penicillin 1 microliter microinjection (100 U) into the caudal nucleus of the spinal tract of the trigeminal nerve, accounting for formation of a generator of pathologically enhanced excitation (GREE), brings about in rats the pain syndrome with characteristic for trigeminal neuralgia behavioural manifestations and the emergence of epileptiform activity in the somatosensory cortex, especially pronounced in the contralateral hemisphere. The emergence of this activity reflects, on the one hand, the action of the GREE in the caudal nucleus of the trigeminal nerve and, on the other hand, the involvement of the somatosensory cortex taking over stimulation from the hyperactive caudal nucleus, into formation of a pathological algic system of this form of trigeminal neuralgia.     

Changes in electric activity of neurons of dorsal raphe nuclei in the development of generator of pathologically enhanced excitation in the nociceptive system

In the experiments on rats it was proved by the method of extracellular registration of impulse neuron activity of dorsal raphe nucleus, that the formation of generator of pathologically enhanced excitation (GPEE) in nociceptive structures of spinal brain underlying the pain syndrome of spinal origin, results in a change of electric neuron activity of dorsal raphe nucleus. These changes are manifested by growing number of background nucleus neurons, the increase of middle frequency of discharges, and assuming pack character of impulse activity. These changes are greater marked in a ventral nucleus part, than in a dorsal one, which is evident of the activation of this antinociceptive system structure. The changes of electric activity of dorsal raphe neurons are stable for a long time after GPEE is formed in nociceptive system, and participate in suppression of GPEE and corresponding pain syndrome.     

Effect of diazepam on the epileptic activity of rats with experimental photogenic epilepsy]

Chronic experiments were conducted on rats. A study was made of the effect of diazepam (in a dose of 4 mg/kg of body weight) on the specific and nonspecific mechanisms of experimentally-induced photogenic epilepsy developing as a result of tetanus toxin injection into the lateral geniculate body (LGB) and formation in this nucleus of a pathologically enhanced excitation generator (PEEG). Diazepam in the mentioned dose had a relatively weak effect on the extent of pathological enhancement of the sensory visual signal in the LGB under conditions of PEEG formation aided detection of focal interictal discharges in this nucleus, and completely inhibited generalized epileptic activity in experimental animals in the course of one hour.     

Formation of an excitation generator in the medullary gigantocellular nucleus following disturbance of inhibition by tetanus toxin

Unit activity was studied in the gigantocellular nucleus of decerebrate cats after injection of tetanus toxin into the nucleus. The toxin was used to disturb inhibition. An increase in amplitude and frequency of unit discharges, a marked increase in integral spontaneous and, in particular, evoked activity, an increase in the number of neurons with a "burst" type of activity, and prolonged maintenance of enhanced evoked activity were recorded in the poisoned nucleus. The increased activity in the part of the poisoned nucleus studied could be temporarily suppressed by injection of glycine into the nucleus or by strong direct electrical stimulation. It can be concluded from the results that a population of neurons with disturbed inhibitory connections forms an excitation generator. The nature of operation of such a generator is discussed and the possibility of simulating neurological syndromes by the creation of such generators in various parts of the CNS is argued.     

Clinico-electroencephalographic indices of the parkinsonian syndrome induced by MPP+ in rats

The bilateral intranigral injection of 1-methyl-4-phenyl-pyridinium ion (MPP+) (10 g) produced significant oligokinesia, rigidity and weak tremor in rats. The extrapyramidal disturbances manifest a high-amplitude paroxysmal activity (PA) in the structures studied. It was found that the Pa was remarkable and more stable in the caudata nucleus than in other brain structures. It is PA that gives us the real basis to conclude the formation of the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei. The analysis of PA dynamics revealed that the formation of the GPEE in the caudata nuclei correlated with development of parkinsonian syndrome (PS).     

Analgesia following electrostimulation of midbrain nuclei of rats with a pain syndrome of spinal origin]

The effect of electrostimulation of the mesencephalic grey matter and of the dorsal nucleus raphe on physiological pain produced by nociceptive stimulation (compression of the tail or the skin on the limb by a clamp) and on pathological pain (the pain syndrome of spinal origin) were studied in experiments on albino rats. Pathological pain was induced by creating a generator of pathologically enhanced excitation in the dorsal horn of the spinal cord by local disturbance of the inhibitory mechanisms with the aid of tetanus toxin. It was shown that electrostimulation of the indicated areas abolished both physiological and pathological pain. A conclusion was drawn that analgesia produced by electrostimulation of certain structure of the brain was connected not only with augmentation of the descending inhibition in the spinal cord as in the case of physiological pain caused by peripheral nociceptive stimulation (as shown by several authors), but also with the block of excitation at the supraspinal level. This mechanism should play a decisive role in analgesia realization in the pain syndrome of central origin, both under experimental and natural conditions.     

脚内核在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨脚内核在电针镇痛及兴奋尾壳核镇痛中的作用。脚内核微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响。与正常对照组电针或兴奋尾壳核产生的抑制作用相比有显著性差异 (P <0 .0 5 ) ;与脚内核微量注射生理盐水 7d后 ,电针可提高大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比 ,有显著性差异 (P <0 0 5 )。上述结果提示 ,脚内核在电针及兴奋尾壳核镇痛中发挥重要作用     

Changes in the functional organization of the lateral geniculate body after tetanus toxin injection

Changes in unit activity in the lateral geniculate body during formation of a generator of pathologically enhanced excitation as a result of local injection of tetanus toxin into this nucleus were investigated in unanesthetized cats. To assess changes taking place a classification of geniculate neurons in normal animals obtained by analysis of interspike interval histograms of spontaneous activity and poststimulus histograms of unit activity evoked by photic stimulation was used. As a result of the action of the toxin substantial changes were observed in the quantitative distribution of the neurons by groups. A new group of neurons with a considerably increased duration of the first spike volley also was identified. The appearance of these neurons is connected with disappearance of the inhibitory pause in the overwhelming majority of relay neurons of the nucleus.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 10, No. 1, pp. 38–43, January–February, 1978.     

Modelling psychosis in cats by creating a generator of pathologically enhanced excitation in one of the septal nuclei

The experiments on adult freely behaving cats have shown that the injection of penicillin into the internal part (TI) of bed nucleus of stria terminalis (BST) caused the formation of the generator of pathologically enhanced excitation (GPEE). This part of BST became hyperactive and played the role of a pathologic determinant which caused the formation of a complex pathologic system and behavioural disorders with catatonia, stereotypy, food rejection, eating of uneatable things, hypoalgesia, zoosocial behavioural changes, depression of different emotions, etc. The development of these disorders was progressing and was accompanied by corresponding electrophysiological activity in TI and other brain structures studied. Coagulation of GPEE zone at the early stages of the process prevented the development of the above disorders.     

The selective role of the nucleus raphe magnus in the mechanisms of analgesia in electrocutaneous pain stimulation, cold stress and the action of morphine

Inhibition of the analgetic activity of systemic morphine and inescapable foot shock in certain moments of the experiment was shown on rats subjected to electrolytic destruction of nucleus raphe magnus. Cold swim stress increased analgesia as compared to the control animals. It is concluded that this formation of the brain is selectively and dynamically involved in mechanisms of various types of analgesia.     

Neuro-pathophysiologic effects during primary hyperactivation of the bed nucleus of the stria terminalis in the rat brain

Penicillin administration into the bed nucleus of stria terminalis (BNST) in the rat brain caused epileptiform activity (EpA)--the formation of the generator of pathologically enhanced excitation (GPEE) in the nucleus. GPEE was registered during the first 3 days. EpA was also detected in the amygdala during 5-8 days, and in the hippocamp during the whole period of registration (2-3 weeks). There was the generalized enhancement of synchronized EpA in the range of 6-10 oscillations per s., in some cases with high-amplitude spindle (7-8 oscillations per s.). 50% of animals had emotional behavioural disorders, a marked fear reaction was observed for a month and more. Some animals demonstrated psychotic-like paroxysms with the elements of stereotypy accompanied by high-frequency low-amplitude EpA. It is suggested that when a primary GPEE in BNST is formed, the structures of septo-hippocampal system (BNST, amygdala, hippocamp) play a role of pathological determinants under the influence of which the pathological system consisting of a number of limbic and extrapyramidal structures is formed. Its activity is clinically manifested in the complex polymorphic neuropathological syndrome.     

Microcirculatory changes in experimental trigeminal neuralgia in rats

Biomicroscopic studies of mesentery in trigeminal neuralgia rats caused by creation of a generator of pathologically enhanced excitation in trigeminal nerve caudal nucleus (injection 0.25-1.0 DLM Tetanus toxin) have shown the microcirculatory disorders, venular permeability, mast cells degranulation, and an increase in lymphatic contractile activity. Microcirculatory disorders intensity and adaptation reaction appearance correlated with trigeminal neuralgia clinical picture.     

The mechanism of arterial hypertension in prolonged electrostimulation of the emotiogenic zones in the rabbit hypothalamus

Continuous arterial hypertension which was still present three months after the experiment was achieved by long-term electrostimulation (4 cycles, 12 days each) of the rabbit hypothalamus paraventricular nucleus (PV). Stimulation of the brain subcortical regions was shown to cause excitation in frontal and occipital regions of the cortex and alteration of neurohormonal state, i.e. increase of glucocorticoid content and decrease of both catecholamines, serotonin and histamine blood level in the animals. It is concluded that pathologic functional system resulting in the development of the arterial hypertension is produced on the basis of the generator of pathologically increased excitation (GPIE) in the PV area.     

红核在肌梭传入抑制伤害性反应中的作用

本实验用玻璃微电极细胞外记录方法, 观察了刺激红核对皮肤强电刺激诱发的大鼠脊髓背角广动力范围（ｗｉｄｅ ｄｙｎａｍｉｃ ｒａｎｇｅ, ＷＤＲ） 神经元长潜伏期反应（Ｃ反应） 的作用, 及红核对琥珀胆碱（ｓｕｃｃｉｎｙｌｃｈｏｌｉｎｅ,ＳＣＨ） 诱发的肌梭传入抑制ＷＤＲ神经元Ｃ反应效应的影响。结果表明： 电刺激红核对ＷＤＲ 神经元Ｃ反应具有抑制作用, 此作用可被静注噻庚啶明显减弱。静脉注射ＳＣＨ 对ＷＤＲ神经元Ｃ反应有明显抑制作用, 损毁单侧红核后,ＳＣＨ 对ＷＤＲ神经元Ｃ反应的抑制效应明显减弱。结果提示,５ＨＴ参与红核的痛下行抑制作用, 在肌梭传入镇痛中红核起着一定的作用     

Prolongation of sleep following creation of a generator of pathologically enhanced excitation in the orbital cortex

Acute experiments on cats showed that injection of tetanus toxin into the orbital cortex (which destroys various types of inhibition) resulted in the formation of a local generator of pathologically enhanced excitation in this cortex area. Chronic experiments showed that cats with such a generator in the orbital cortex developed pathological changes of sleep, expressed in reduction of the duration of wakefulness and development of the slow-wave and paradoxical sleep phases being, retained. The results of this investigation confirm the view on the participation of the orbitofrontal cortex in sleep induction. They are in favour of the general conception on the role of the determinant structure in the nervous system activity and the theory of the generator mechanisms of the neuropathological syndromes characterized by the hyperactivity of the system.     

Role of limbic structures in the mechanisms of post-traumatic epilepsy]

It was shown in the experiments on rats that intracerebroventricular administration of kainic acid (0.01, 0.05 microgram) after brain trauma, resulted in the occurrence of behavioral and electrographic convulsive disturbances; maximal expression of epileptic activity was obtained in entorhinal cortex and ventral hippocampus. Kainic acid induced epileptic reactions in nontraumatized rats only if injected in dose 0.1 microgram. Brain trauma did not lead to changes in seizures intensity induced by systemic picrotoxin administration. It is concluded that the formation of generator of pathologically enhanced excitation in limbic structures via increase of excitor glutamatergic neurotransmission is the important mechanism of traumatic epilepsy.     

Appearance of parkinsonian syndrome after administration of delta sleep-inducing peptide into the rat substantia nigra

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.     

Quantitative characteristics of ultrastructural changes in axo-dendritic synapses under the influence of tetanus toxin

Changes in synaptic ultrastructure of the external geniculate body (EGB) were investigated in rats when a generator of pathologically intensified excitation (GPIE) was produced in this nucleus under the influence of tetanus toxin (TT). At the period of pronounced convulsive activity (24 h after TT injection), synaptic changes were estimated electronmicroscopically and with quantitative comparison of the materials from three groups. The first group included EGB synapses where TT was injected, the second group included contralateral EGB synapses and the third included EGB from the rats injected with inactivated toxin. By means of electron optic computer "Klassimat" average amount of round, flat, anomalous and adjacent to the presynaptic membrane vesicles was measured, average relative length of the active zone, average area of the presynaptic terminal, average relative section areas of pre- and postsynaptic cytoplasm condensation were estimated. In the area of GPIE formation, under the influence of TT, the increased amount of the vesicles related to the presynaptic membrane and that of flat vesicles were statistically significant. At the same time, the synaptic terminals, by the number of vesicles, have bimodal, while the control groups have unimodal distribution.     

Effects of excitation of the central nuclei of the cerebellum on the activity of neurons in the pyramidal tract

The effect of excitation of the contralateral nuclei of the cerebellum on the activity of anti-dromically-identified fast and slow pyramidal neurons in the sensorimotor region (SMR) of the cerebral cortex was investigated in delicate experiments on unnarcotized cats immobilized with procurane. It was found that excitation of the above nuclei could evoke peak responses in the neurons of the pyramidal tract (PT), but more often it modified their background activity. These responses were more pronounced on excitation of the intermediate nucleus (IN) or the dentate nucleus (DN), although they also often arose on excitation of the fastigial nucleus (FN). Qualitatively different effects (stimulative and inhibitory) were observed in some neurons on excitation of different nuclei in the cerebellum. It was found that the nature of the responses by fast neurons in the PT to excitation of the central nuclei in the cerebellum did not differe substantially from the nature of the responses by slow neurons, but that the responses of the latter arose with a longer latent period, and in most cases were less pronounced.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 22–31, January–February, 1971.