Investigation of pallidofugal influences on hypothalamic activity

In chronic experiments on nine cats electrical stimulation of the posterior zones of the lateral hypothalamus led to reproduction of a conditioned food-getting reflex produced previously in response to clicks. During stimulation of the globus pallidus a food-getting reflex also appeared in 3 of 10 zones studied, but it did so only irregularly. In response to combined stimulation of the hypothalamus and these three zones of the globus pallidus facilitation of this reflex was observed: its intensity was increased and its latent period shortened. Stimulation of other areas of the globus pallidus inhibited the food getting reflex of hypothalamic origin on account of the intensification of purposeless motor responses. Stimulation of the globus pallidus evoked desynchronization of spontaneous hypothalamic electrical activity. After bilateral electrolytic destruction of the globus pallidus and its principal efferent pathway (the ansa lenticularis) no conditioned food-getting reflex was reproduced during hypothalamic stimulation. After pallidectomy the amplitude of the spontaneous waves and evoked potentials was reduced by a statistically significant degree in the hypothalamic zones tested. The results are evidence of the existence of regulatory functional influences of the globus pallidus on the lateral hypothalamus.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 6, No. 6, pp. 592–601, November–December, 1974.     

Role of the caudate nucleus in the development of evoked synchronized activity

Synchronized activity (spindles, augmentation response) evoked by stimulation of thalamic nonspecific, association, and specific nuclei was investigated in chronic experiments on 11 cats before and after successive destruction of the caudate nuclei. After destruction of the caudate nuclei the duration of spindle activity in the frontal cortex and subcortical formations (thalamic nuclei, globus pallidus, putamen) was reduced to only three or four oscillations. In the subcortical nuclei its amplitude fell significantly (by 50±10%); in the cortex the decrease in amplitude was smaller and in some cases was not significant. Different changes were observed in the amplitude of the augmentation response, depending on where it was recorded. In the subcortical formations it was considerably and persistently reduced (by 50±10%); in the cortex these changes were unstable in character. Unilateral destruction of the caudate nucleus inhibited synchronized activity evoked by stimulation of the thalamic nuclei on the side of the operation only. Destruction of the basal ganglia (caudate nucleus, globus pallidus, entopeduncular nucleus, and putamen) did not prevent the appearance of synchronized activity; just as after isolated destruction of the caudate nucleus, after this operation synchronized activity was simply reduced in duration and amplitude. It is suggested that the caudate nucleus exerts an ipsilateral facilitatory influence on the nonspecific system of the thalamus during the development of evoked synchronized activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 3, pp. 239–248, May–June, 1977.     

Synaptic processes in red nucleus neurons produced by stimulating the entopeduncular nucleus and globus pallidus in the cat

Synaptic processes in red nucleus neurons produced by stimulating the entoped-uncular nucleus and the globus pallidus were investigated during acute experiments on cats using intracellular recording techniques. It was found that stimulating these structures produces mono- and polysynaptic excitation of rubrospinal neurons. Analysis of the time parameters of the EPSP recordings obtained suggested that they were produced by activation of the axosomatic and axodendritic synapses of rubrospinal neurons. Mechanisms of basal ganglia involvement in the integrating of red nucleus activity are examined.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 809–817, November–December, 1985.     

Effect of stimulation of the caudate nucleus on activity of neurons of the globus pallidus

Activity of neurons of the globus pallidus was recorded extracellularly during stimulation of the caudate nucleus. It is demonstrated that background activity (BA) of most neurons of the globus pallidus is depressed under these conditions, which is regarded as a manifestation of inhibition of the investigated neurons. The period of BA depression varied in different cells from 60 to 500 msec. In some cases this period was preceded by emergence of an action potential with a latent period of 10–20 msec. In addition to inhibition of the activity of globus pallidus neurons during stimulation of the caudate nucleus, it was possible to record evoked responses of the given neurons in the form of group discharges with a latent period of 18–40 msec and single action potentials with a latent period of 50–100 msec. The neurons that reacted with a shorter latent period were localized at the lateral limit of the globus pallidus, whereas neurons with other kinds of responses were distributed in the globus pallidus comparatively evenly.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 202–209, September–October, 1969.     

Responses of cat cerebellar cortical neurons to stimulation of the caudate nucleus,globus pallidus,and substantia nigra

Stimulation of the head of the caudate nucleus in cats anesthetized with chloralose and pentobarbital evoked spike responses of the Purkinje cells and other cerebellar cortical neurons in the paramedian lobes, lobulus simplex, and the tuber of the vermis. Phasic responses in the form of simple discharges (on account of activation of the neurons through mossy fibers) appeared mainly after a latent period of 5–12 and 14–20 msec; the latent period of responses consisting of complex discharges (on account of activation of Purkinje cells through climbing fibers) was 5–6, 9–22 msec, or more. Depending on the latent period, the spike responses differed in their rhythm of generation. In response to stimulation of the caudate nucleus with a frequency of 4–6/sec recruiting responses were found. An inhibitory pause was an invariable component of the tonic responses. During stimulation of the globus pallidus responses of the same types (phasic and tonic) appeared as during stimulation of the caudate nucleus, but they differed in the distribution of the neurons by latent period of spike responses. The minimal latent period was 4 msec. Recruiting also was observed during repetitive stimulation of the globus pallidus. During stimulation of the substantia nigra Pukinje cells activated by climbing fibers responded. Evoked complex discharges appeared after a stable latent period of 8.5±0.3 msec. Arguments are put forward regarding the role of the substantia nigra, the globus pallidus, nuclei of the inferior olive, and also the thalamic nuclei in the mechanism of caudato-cerebellar oligosynaptic and polysynaptic connections.N. I. Pirogov Medical Institute, Vinnitsa. Translated from Neirofiziologiya, Vol. 10, No. 4, pp. 375–384, July–August, 1978.     

Changes in evoked potentials during differentiation inhibition

Evoked responses (EPs) of the auditory and the sensorimotor cortical areas were studied in experiments on cats during formation of a positive food-procuring conditioned reflex to a rhythmic sequence of clicks and during formation of the differentiation inhibition in response to the clicks of the same parameters, but with different frequency. In the positive conditioned reflex the EPs amplitude in the sensorimotor cortex increases; they are enriched by late components and in their general configuration they become much similar to EPs in the auditory area. The EPs patterns both in the auditory and in the sensorimotor areas considerably change in response to the differentiation stimulus, but differently in each of the sites.     

Responses of caudate neurons to clicks in chronic experiments on cats

Spontaneous and evoked unit activity in response to repeated application of clicks at a frequency of 0.3–2.0 Hz in the caudate nucleus was studied by an extracellular recording technique in chronic experiments on cats. Four types of spontaneous unit activity in the caudate nucleus were distinguished. Altogether 44% of neurons tested responded by changes in spontaneous activity to clicks. Five types of responses of caudate neurons to clicks were discovered: phasic excitation, phasic inhibition, tonic activation, tonic inhibition, and mixed tonic responses; the commonest type was tonic activation. During prolonged stimulation by clicks extinction of the phasic responses was not observed. Complete or partial extinction of tonic responses in the course of frequent repetition of stimulation was observed in 33% of responding neurons. The question of possible convergence of specific and nonspecific influences on caudate neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 28–35, January–February, 1980.     

Differentiation of efferent projections of the medial (cuneiform nucleus) and lateral regions of the reticular formation in cat midbrain

Efferent connections of medial (nucleus cuneiformis) and lateral regions of the midbrain reticular formation (MRF) were investigated using an anterograde autoradiographic technique in cats. Efferent fibers from the MRF ascend to the globus pallidus, substantia innominata, hypothalamus, subthalamus, and nonspecific associative and relay nuclei of the thalamus. Descending pathways to the conclusion that the cuneiform nucleus is more of a nonspecific structure than an association auditory center. The lateral reticular region had numerous projections to the lateral geniculate body and, together with the parabigeminal nucleus, forms the midbrain visual complex.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 646–652, September–October, 1985.     

Responses of caudate neurons to acoustic stimulation in cats

Responses of 141 neurons of the caudate nucleus to acoustic stimuli — tones (500 and 2000 Hz) and clicks of different frequency (0.2 and 0.8/sec) and intensity (75, 80, 95 dB) — were recorded extracellularly in chronic experiments on cats. The responses recorded showed great variability with respect to character (phasic, tonic), structure (one or two phases of excitation), latent periods (from 7.5 to 300.0 msec), and burst discharge frequency (from 90 to 800 spikes/sec). Analysis of averaged poststimulus histograms and graphs of the dynamics of the responses showed that responses of 74% of neurons were much better expressed if less frequent stimuli were used: The regularity of the responses and the number of spikes in each response increased. Responses of neurons also increased and acquired a more distinct temporal structure if the intensity of the clicks increased. The character of responses to clicks and tones differed qualitatively in 17% of neurons studied: Phasic excitation arose in response to clicks, tonic changes in spike activity to tones. The particular features of responses of caudate neurons to acoustic stimulation with different parameters are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 588–595, November–December, 1980.     

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.     

Differential Regional Effects of Methamphetamine on the Activities of Tryptophan and Tyrosine Hydroxylase

Abstract : Administration of high doses of methamphetamine (METH) produces both short- and long-term enzymatic deficits in central monoaminergic systems. To determine whether a correlative relationship exists between these acute and long-term consequences of METH treatment, in the present study we examined the regional effects of METH on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities in various regions of the caudate nucleus, nucleus accumbens, and globus pallidus. A single METH administration decreased TPH activity 1 h after treatment in the globus pallidus, in the nucleus accumbens, and throughout the caudate ; in the anterior caudate, the ventral-medial was more affected than the dorsal-lateral region. In contrast, TH activity was not decreased in either the caudate or the globus pallidus after a single METH administration ; however, it was altered in the nucleus accumbens. Seven days after multiple METH administrations, TH and TPH activities were decreased in most caudate regions but not in the nucleus accumbens or globus pallidus. These data demonstrate that (1) the effects of METH on TPH and TH vary regionally ; and (2) the short-term and long-term regional responses of TPH to METH in the caudate and globus pallidus correlated. In contrast, METH-induced acute TH responses did not predict the long-term changes in TH activity.     

Myelo- and cytoarchitectonics of the feline globus pallidus

A powerful system of strictly oriented unmyelinated and myelinated axons 0.2–0.7 µ in diameter running en passant through the dorsal part of the putamen and globus pallidus toward the basis pedunculi was discovered by a controlled impregnation method in thick frontal and sagittal sections through the cat brain. The nerve-fiber composition of these en passant bundles, the character of their formation and orientation, and their course were studied in detail. The cyto- and synaptoarchitectonics of the globus pallidus were investigated. According to approximate calculation the number of axons contained in these en passant bundles in the globus pallidus of one hemisphere in the cat is not less than 10 million, and the number of neurons is about 8000. The need for an essential revision of the interpretation of the results of physiological and morphological investigations involving procedures aimed directly at the globus pallidus and with the partial or total destruction of that formation is discussed in connection with the new data obtained on the structure of the globus pallidus (the presence of comparatively few neurons belonging to the globus pallidus itself and a huge number of thin en passant axons).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 321–328, July–August, 1979.     

Responses of units in the magnocellular part of the medial geniculate body to acoustic and somatosensory stimulation

Responses of 150 neurons in the magnocellular part of the medial geniculate body to clicks and to electrodermal stimulation of the contralateral forelimb were investigated in cats immobilized with myorelaxin. Of the total number of neurons 65% were bimodal, 16.6% responded only to clicks, and 15.4% only to electrodermal stimulation. The unitary responses were excitatory (spike potentials) and inhibitory (inhibition of spontaneous activity). Responses beginning with excitation occurred more frequently to stimulation by clicks than to electrodermal stimulation, whereas initial inhibition occurred more often to electrodermal stimulation. The latent period of the initial spike potentials in response to clicks and to electrodermal stimulation was 5–27 and 6–33 (mean 11.6 and 16.2) msec respectively. Positive correlation was found between the latent periods of spike potentials recorded in the same neurons in response to clicks and to electrodermal stimulation, and also to electrodermal stimulation and to stimulation of the dorsal funiculus of the spinal cord. It is concluded that the magnocellular division of the medial genicculate body is a transitional structure between the posterior ventral nucleus and the parvocellular division of the medial geniculate body, and that in addition, it is connected more closely with the auditory than with the somatosensory system. It is suggested that the somatosensory input into the magnocellular division of the medial geniculate body is formed mainly by fibers of the medial lemniscus.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 133–141, March–April, 1978.     

Responses of neurons of reticular and ventral anterior nuclei of the cat thalamus to afferent stimuli of different modalities

Responses of 146 spontaneously active neurons of the reticular nucleus (R) and of 98 neurons of the ventral anterior (VA) nucleus of the thalamus to electrical stimulation of the skin of the footpads, to flashes, and to clicks were studied in experiments on cats immobilized with D-tubocurarine or myorelaxin. Stimulation of the contralateral forelimb was the most effective: 24.9% of R neurons and 31.3% of VA neurons responded to this stimulation. A response to clicks was observed in only 4.4% of R neurons and 2.4% of VA neurons. Nearly all responding neurons did so by phasic (one spike or a group of spikes) or tonic excitation. Depression of spontaneous activity was observed only in response to electrical stimulation of the skin. Depending on the site of stimulation, it was observed in 2.6–4.3% of R neurons and 1.7–2.1% of VA neurons tested. The latent period of the phasic responses of most neurons was 6–64 msec to electrical stimulation of the contralateral forelimb, 11–43 msec in response to stimulation of the hindlimb on the same side, 10–60 msec to photic and 8–60 msec to acoustic stimulation. Depending on the character of stimulation, 75.1–95.6% of R neurons and 68.7–97.6% of VA cells did not respond at all to the stimuli used. Of the total number of cells tested against the whole range of stimuli, 25% of R neurons and 47% of VA neurons responded to stimulation of different limbs, whereas 16% of R neurons and 22% of VA cells responded to stimuli of different sensory modalities. The functional role of the convergence revealed in these experiments is to inhibit (or, less frequently, to facilitate) the response of a neuron to a testing stimulus during the 40–70 msec after conditioning stimulation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 7, No. 6, pp. 563–571, November–December, 1975.     

苍白球γ-氨基丁酸能神经传递及其与神经系统疾病的关系

苍白球是基底神经节间接环路的重要核团,在机体运动功能调节中发挥重要作用。近年来,苍白球在基底神经节正常及异常功能调节中的重要性已日渐受到重视。然而,目前对苍白球内各种神经递质系统的功能活动了解较少。GABA是苍白球主要的神经递质。采用电生理记录、免疫组织化学及行为测试等实验方法,人们对大鼠苍白球GABA能神经传递系统的受体分布及功能活动有了新的认识。形态学研究揭示,苍白球存在GABAA受体及其苯二氮卓结合位点和GABAB受体。在亚细胞水平,GABAA受体主要位于对称性突触(GABA能突触)的突触后膜,而GABAB受体则位于对称性突触和非对称性突触(兴奋性突触)的突触前膜及突触后膜。功能学研究进一步揭示,激活苍白球突触前膜GABAB自身和异源性受体可分别减少GABA和谷氨酸释放;激活突触后膜GABAB受体,可引起苍白球神经元超极化。除GABAB受体外,激活苍白球GABAA受体苯二氮卓结合位点及阻断GABA重摄取可延长GABA电流持续时间,从而改变苍白球神经元兴奋性。与离体实验结果相一致,激活苍向球GABAB受体和苯二氮卓结合位点及阻断GABA重摄取可引起整体动物旋转行为。苍白球GABA神经递质系统与帕金森病病因学及癫痫发病有关。已证实,苍白球神经元放电频率的降低及簇状放电的产生与帕金森病运动减少及静止性震颤等症状直接相关。此外,电牛理及行为学实验发现,新型抗癫痫药物替加平可调节苍白球神经元功能活动．这为进一步了解苍白球与癫痫发病的关系提供了新的理论及实验依据。     

Afferent connections of the cat caudate nucleus studied by the retrograde axonal transport method

Sources of direct and indirect afferent connections of the caudate nucleus were investigated in cats by the retrograde axonal transport of horseradish peroxidase method. Different parts of the neocortex were shown to form different types of projections to the caudate nucleus; the sources of these projections have a laminar organization. Connections of the globus pallidus with the caudate nucleus, not previously described, were found. Among the sources of the thalamo-caudate projections, besides nuclei of the intralaminar complex, an important place is occupied by the ventral anterior and mediodorsal nuclei. After injection of horseradish peroxidase into the caudate nucleus, retrograde axonal transport of the enzyme was observed in the caudal direction, as far as cells of the locus coeruleus. ON the basis of these results a general scheme of afferent projections to the caudate nucleus is drawn up, including its connections with the spinal cord mediated by the thalamic nuclei and mesencephalic reticular formation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 2, pp. 146–154, March–April, 1980.     

Connections between the globus pallidus and putamen and the hypothalamus and subthalamus

In 16 adult cats with electrolytically destructed external and internal parts of the globus pallidus and in 8 cats with destructed putamen direct strio-pallido-hypothalamic and strio-pallido-subthalamic pathways have been studied. Degeneration of the axonal preterminals and terminals have been examined in preparations treated after Nauta--Gygax, Nauta--Laidlow, Finck--Heimer with simultaneous additional staining of the nuclei with cresyl violet after Kawamura--Niimi. Direct pallido- and putamen-hypothalamic pathways to nuclei of the grey tubercle, posterior and lateral nuclei of the hypothalamus were stated. Direct pathways from the putamen to the subthalamic nucleus have been revealed, however, these pathways are represented in less degree than those of pallido-subthalamic connections. Direct pathways from the external portion of the globus pallidus and putamen to the subthalamic nucleus are more pronounced and represented by greater numbers of projections than those of strio-pallido-hypothalamic origin.     

Electrophysiological analysis of corticofugal influences on preoptic neurons

Evoked potential (EPs) and responses of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent structures of the hypothalamus to stimulation of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. The most pronounced EPs were observed in the RPO after stimulating the piriform and cingulate cortex. A close relation was found between neuronal responses and EP components. The majority of neurons responding to stimulation of various cortical structures were localized in the LPO, where primarily excitatory responses dominate. The MPO contained somewhat fewer neurons responding to cortical stimulation, and the dominant response here was primarily inhibitory. The ratio of inhibitory and excitatory responses in the LPO was 0.6:1 and in the MPO 5.8:1. Primarily in-inhibitory responses dominated also in the LPO zone adjacent to the bed nucleus stria terminalis (BST) and primarily excitatory in the region surrounding the supraoptic nucleus (SO) (respective ratios 4.9:1 and 0.7:1). The RPO is a broad convergence zone, where 3/4 of the neurons responded to stimuli of two and more cortical regions.A. M. Gorky Medical Institute, Ukrainian Minstry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 709–719, November–December, 1991.     

Inhibitory and excitatory processes in thalamic motor nuclei neurons in the normal nigrostriatal dopaminergic system and following injury to it produced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Excitatory and inhibitory processes in neurons of the thalamic anteroventral and ventrolateral (VA–VL) motor nuclei were investigated in two sets of experiments on cats anesthetized with Ketalar and immobilized by myorelaxant during the course of stimulation of the red nucleus region and following chronic administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5 mg/kg i.m. over a 5-day period): It was found 48 h after the last MPTP injection that up to 48% neurons belonging to the substantia nigra pars compacta had been destroyed and that dopamine level had declined to 30% of that found in intact animals. In cats injected with MPTP inhibitory processes declined significantly in both duration and efficacy in VA–VL relay and non-relay neurons, while latency of orthodromic excitatory response to red nucleus stimulation declined. It is suggested that attenuation of dopamine-modulated GABA-ergic nigrothalamic influences underlies the low level of inhibition occurring.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Institute of Endocrinology and Metabolism, Ukrainian Ministry of Public Health, Kiev. Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 620–629, September–October, 1989.     

Analysis of spike discharge and character of interconnection of identified output neurons in the rat neostriatum

Two populations of neostriatal neurons projecting into the globus pallidus and two neuron populations projecting into the substantia nigra were identified by antidromic testing in acute experiments on immobilized rats. Statistical analysis showed that the firing patterns of the identified output neurons were of either the grouped or single type. Cross-correlation analysis of the spontaneous activity of two neurons, one projecting into the substantia nigra, the other into the globus pallidus, showed that activity of the second neuron was inhibited for 300–400 msec after spike generation by the first neuron.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Computer Research Center, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 14, No. 5, pp. 470–475, September–October, 1982.