Excitatory effect of subthalamo-nigral and subthalamo-pallidal efferent pathways in the rat

Microinjections of the GABA antagonist, bicuculline, where shown to selectively activate subthalamic neurons in the rat. Stimulation of subthalamic efferent pathways increased the neuronal discharge in the pallidal complex and pars reticulata of the substantia nigra. Most nigral dopaminergic neurons displayed a slight decrease in firing rate. According to these results, which are more coherent than those obtained through electrical stimulation, the subthalamic nucleus may be considered a source of tonic activation of the two output structures of the basal ganglia viz, pars reticulata of the substantia nigra and entopeduncular nucleus.     

尾核P物质对胃运动的抑制效应系通过黑质,迷走背核经迷走神经所介导

本工作观察损毁下丘脑外侧区,黑质,迷走背核及其传出神经对尾核微量注射Ｐ物质引起的胃肌电快波和胃运动抑制效应的影响。实验结果：该抑制效应不依赖于下丘脑外侧区的完整但可被损毁黑质,迷走背核或迷走上所消除。用利血平耗竭交感神经递质则不影响该效应。这些结果表明：尾核ＳＰ的抑胃效应系通过黑质、迷走背核经迷走神经所传出。     

大白鼠脚内核的传入性联系

众所周知,肉食动物和大白鼠的脚内核,相当于灵长类的内侧苍白球(Nagy et al.1978;Fox and Schmitz 1944);它们的细胞形态、传入及传出均相同。早期以及近年来的一些研究工作者,虽然在研究其他核团的投射时,联系到一些本核团的传入,但是尚缺乏对本核团传人的系统研究。本实验即是应用辣根过氧化物酶的逆行传递法来研究大白鼠脚内核的传入性联系。     

Comparison of the Connectional Properties of the Two Forelimb Areas of the Rat Sensorimotor Cortex: Support for the Presence of a Premotor or Supplementary Motor Cortical Area

The existence of multiple motor cortical areas that differ in some of their properties is well known in primates, but is less clear in the rat. The present study addressed this question from the point of view of connectional properties by comparing the afferent and efferent projections of the caudal forelimb area (CFA), considered to be the equivalent of the forelimb area of the primary motor cortex (MI), and a second forelimb motor representation, the rostral forelimb area (RFA). As a result of various tracing experiments (including double labeling), it was observed that CFA and RFA had reciprocal corticocortical connections characterized by preferential, asymmetrical, laminar distribution, indicating that RFA may occupy a different hierarchical level than CFA, according to criteria previously discussed in the visual cortex of primates. Furthermore, it was found that RFA, but not CFA, exhibited dense reciprocal connections with the insular cortex. With respect to their efferent projection to the basal ganglia, it was observed that CFA projected very densely to the lateral portion of the ipsilateral caudate putamen, whereas the contralateral projection was sparse and more restricted. The ipsilateral projection originating from RFA was slightly less dense than that from CFA, but it covered a larger portion of the caudate putamen (in the medial direction); the contralateral projection from RFA to the caudate putamen was of the same density and extent as the ipsilateral projection. The reciprocal thalamocortical and corticothalamic connections of RFA and CFA differed from each other in the sense that CFA was mainly interconnected with the ventrolateral thalamic nucleus, while RFA was mainly connected with the ventromedial thalamic nucleus. Altogether, these connectional differences, compared with the pattern of organization of the motor cortical areas in primates, suggest that RFA in the rat may well be an equivalent of the premotor or supplementary motor area. In contrast to the corticocortical, corticostriatal, and thalamocortical connections, RFA and CFA showed similar efferent projections to the subthalamic nucleus, substantia nigra, red nucleus, tectum, pontine nuclei, inferior olive, and spinal cord.     

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.     

The role of the substantia nigra in the control of amygdaloid paroxysmal activity

Both in acute and chronic cats focal paroxysmal activity evoked in the ventro-basal complex of the amygdala has been inhibited by substantia nigra conditioning stimulation, to a greater extent, than by caudate nucleus activation. Injection of kainic acid into substantia nigra resulted in the disappearance of the caudate inhibition. It is suggested that the final control, exerted by the striatum on the amygdaloid seizures, occurs by means of the substantia nigra.     

Effect of beta-phenylethylamine on evoked potentials of the neostriatum of rats]

The effect of intraperitoneal (70 mg/kg) and local (39 ug) administration of beta-phenylethylamine (beta-PEA) on evoked potentials (EP) in the caudate nucleus upon stimulation of substantia nigra zona compacta (SNC) and frontal cortex in rats has been studied. beta-PEA, glutamate and haloperidol were injected into the caudate nucleus by means of a system consisting of a pushpull cannule and an electrode for simultaneous registration of EP. Specificity in the effect of the drugs on EP in response to stimulation of the cortex and substantia nigra was revealed. The intraperitoneal injection of beta-PEA induced, comparatively to the application, more rapid and potent decrease in the amplitude of the component (N2-P2) as a result of the substantia nigra stimulation and slightly influenced the EP amplitude in stimulation of the frontal cortex. It was established using haloperidol that the component (N2-P2) of EP in response to the substantia nigra stimulation is of dopaminergic neuron function in the nigro-neostrital system of the rat brain.     

Distribution of horseradish peroxidase-labeled neurons giving rise to descending fiber systems in the basal ganglia and hypothalamus in cats

The distribution of neurons giving rise to various descending fiber systems to brain-stem structures in the basal ganglia (including amygdaloid nuclei) and hypothalamus of the cat was studied by the retrograde axonal transport of horseradish peroxidase method. Neurons in the medial part of the central nucleus and of the magnocellular part of the basal nucleus of the amygdaloid group were shown to send axons to the dorsal hippocampus, substantia nigra, lateral part of the central gray matter, and the mesencephalalic reticular formation and also to the region of the locus coeruleus and the lateral medullary reticular formation at the level of the inferior olives. The predominant source of projections to the hypothalamus and brainstem structures is the central amygdaloid nucleus, which also sends projections to the nucleus of the tractus solitarius, the dorsal motor nucleus of the vagus nerve, and the superior cervical segments of the spinal cord. Uncrossed fiber systems descending from the basal ganglia terminate at the level of the pons, whereas uncrossed and crossed fiber systems descending from the dorsal and ventromedial hypothalamus can be traced into the spinal cord. The possible role of nuclei of the amygdaloid group, the hypothalamus, and their efferent projections in the regulation of somatic and vegetative functions and also of complex behavioral reactions is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 14–23, January–February, 1981.     

Differential effect of psychotropic drugs on dihydroxyphenylacetic acid (DOPAC) in the rat substantia nigra and caudate nucleus

The effect of different psychotropic drugs on DOPAC levels in the caudate nucleus and in the substantia nigra was compared. While pargyline, haloperidol and damphetamine caused parallel changes in both areas, apomorphine and reserpine influenced DOPAC levels in the caudate nucleus and in the substantia nigra differently. In both areas pargyline caused a rapid fall in DOPAC concentrations, while haloperidol caused a marked increase. D-amphetamine was slightly more potent in decreasing DOPAC level in the substantia nigra than in the caudate nucleus. On the other hand, apomorphine was very potent in decreasing DOPAC level in the caudate nucleus but failed to influence it in the substantia nigra. Finally, reserpine, which depleted dopamine stores in both areas, increased DOPAC in the caudate nucleus but decreased it in the substantia nigra.     

GABA in the entopeduncular nucleus and the subthalamic nucleus participates in mediating dopaminergic striatal output functions

The bilateral intracerebral injection of the specific GABA agonists muscimol (25, 100 ng) and THIP (500 ng) into the pallido-entopeduncular nucleus (EP) and the subthalamic nucleus (STN) of rats induced a behavioural stimulation closely resembling the syndrome evoked by direct stimulation of dopamine receptors in the striatum or by the systemic injection of dopamine agonists. The rats showed strong locomotor and rearing activity followed by characteristic stereotyped behaviour consisting of sniffing and gnawing activity. The stimulation induced by muscimol (25 ng) was found independent of dopamine, since the dopamine antagonist haloperidol (1 mg/kg s.c.) induced no blockade. Injection of the GABA antogonist picrotoxin (100 ng) into the EP or STN induced sedation and catalepsy. The unilateral injection of muscimol and picrotoxin provoked contraversive and ipsiversive postural changes. Related behavioral effects were induced by GABAergic drugs injected in substantia nigra, zona reticulata (SNR). These data provide support for the new hypothesis that GABA in the EP, SNR and STN is important for the expression of behavior related to stimulation of dopamine receptors in the striatum. The effects may be induced by a dopamine activation of the descending striato-EP, striato-SNR GABAergic pathways and possibly also the pallido-STN GABAergic pathway. The findings suggest that in addition to a pathology of the dopamine system there may also be a GABAergic dysfunction in the efferent system of the basal ganglia localized to the EP, SNR and STN in diseases, such as parkinsonism, Huntington's chorea and possibly schizophrenia.     

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.     

Influence of neurotensin on behavior of rats with lesions in serotonergic neurons

After serotonergic lesion by administration of 5,7-dihydroxytryptamine into the dorsalis raphe nucleus, effects of neurotensin microinjections into the caudate nucleus and substantia nigra on rat behavior were compared. Serotonergic lesions resulted in motivated excitement of rats manifested as an increase in the number of intersignal motor reactions during realization and, particularly, extinction of thirst conditioned reflex. Neurotensin microinjections into the caudate nucleus facilitated extinction of the conditioned reflex both in operated and control rats, but such microinjection into the substantia nigra facilitated this process only in operated animals. Neurotensin did not change conditioned reflex realization in both groups of animals but decreased emotional excitement of rats in the "open field". The behavioral effects of neurotensin in operated rats are connected with normalization of motivational and emotional states of animals and may be explained by recovery of interaction between the dopamine- and serotonergic systems. It is suggested that the mechanisms of this normalizing effects of neurotensin at the levels of the caudate nucleus and substantia nigra are different and are associated preferentially with its action either on dopamine- or serotonergic structures.     

In vivo release of adenosine from cat basal ganglia—studies with a push pull cannula

The release of newly synthesized [³H]adenosine has been studied in vivo in cat caudate nucleus and substantia nigra, using a push pull cannula. In the presence of [³H]adenosine as precursor, spontaneously released [³H]adenosine was easily detectable in superfusates of the push pull cannula. In the caudate nucleus, potassium and veratridine caused a marked and reversible increase in [³H]adenosine release. The effect of veratridine was completely blocked by tetrodotoxin (TTX) although TTX had no action by itself. Ouabain as well as glutamate, also markedly increased the release of [³H]adenosine.The specific 5′ nucleotidase inhibitor α,β-methylene ADP, did not alter the increase in the amount of [³H]adenosine obtained by veratridine, although it diminished the spontaneous release of [³H]adenosine by about 20%.Push pull cannulae were also implanted simultaneously into the caudate nucleus and substantia nigra. Potassium applied into the caudate nucleus increased the local release of adenosine but did not change that observed in the substantia nigra. When potassium was applied into the substantia nigra, it also increased the local release of adenosine but did not change that observed in the caudate nucleus.The results are discussed in term of the possible existence of “purinergic neurons” and of the relation between the adenosine release and central nervous activity.     

Efferent connections of the centrum medianum of the cat thalamus revealed by autoradiography

Efferent connections of the centrum medianum and parafascicular nucleus of the thalamus (CM-Pf complex) in cats were studied by the method of anterograde axonal transport of tritiated amino acids followed by autoradiography. Projections from CM-Pf ascend to nuclei of the ventral group and nonspecific nuclei of the thalamus, preoptic, dorsal, lateral, and posterior areas of the hypothalamus, and also into the subthalamic region. Descending pathways are formed only by neurons of the caudomedial part of CM-Pf. They project into the pretectal region, superior colliculus, reticular formation, locus coeruleus, region of the ramus communicans, and substantia grisea centralis of the mesencephalon and pons, and also into the nuclei raphe, magnocellular reticular area, and inferior olivary nucleus of the medulla. In agreement with previous observations it was found that the caudomedial part of CM-Pf does not send direct projections into the cortex and striatum.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 224–230, March–April, 1984.     

The Subcortical Cocktail Problem; Mixed Signals from the Subthalamic Nucleus and Substantia Nigra

The subthalamic nucleus and the directly adjacent substantia nigra are small and important structures in the basal ganglia. Functional magnetic resonance imaging studies have shown that the subthalamic nucleus and substantia nigra are selectively involved in response inhibition, conflict processing, and adjusting global and selective response thresholds. However, imaging these nuclei is complex, because they are in such close proximity, they can vary in location, and are very small relative to the resolution of most fMRI sequences. Here, we investigated the consistency in localization of these nuclei in BOLD fMRI studies, comparing reported coordinates with probabilistic atlas maps of young human participants derived from ultra-high resolution 7T MRI scanning. We show that the fMRI signal reported in previous studies is likely not unequivocally arising from the subthalamic nucleus but represents a mixture of subthalamic nucleus, substantia nigra, and surrounding tissue. Using a simulation study, we also tested to what extent spatial smoothing, often used in fMRI preprocessing pipelines, influences the mixture of BOLD signals. We propose concrete steps how to analyze fMRI BOLD data to allow inferences about the functional role of small subcortical nuclei like the subthalamic nucleus and substantia nigra.     

Distribution of tyrosine hydroxylase in human and animal brain

The activity of tyrosine hydroxylase (EC 1.10.3.1) when assayed under ideal conditions in young human brains, was comparable to that in brains of other species in level of activity and distribution. The highest levels of activity were in the putamen, caudate nucleus and substantia nigra, in keeping with data on other species. The caudate activity in human brain appeared to decrease substantially with increasing age. In both humans and baboons, the enzyme in the neostriatum was particle-bound and inhibited by the 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine cofactor system. In the substantia nigra it was soluble and stimulated by the 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine cofactor system. The data suggest that tyrosine hydroxylase may be produced in a soluble form in the cell bodies of the substantia nigra but become bound as it moves toward the nerve endings in the putamen and caudate nucleus. The bound form of the enzyme was unstable but the soluble form exhibited considerable stability.     

Electrophysiological characteristics of caudate-thalamic connections

Functional connections between different parts of the caudate nucleus and particular thalamic nucleic were investigated during the onset and development of the recruiting response in chronic experiments on cats. The method of condioning and testing stimulation of subcortical structures was used. The highest degree of functional connection was observed between the caudate nucleus and ventral anterior thalamic nucleus in the ipsilateral hemisphere. It is suggested that caudatethalamic functional connections in the development of synchronized activity are due to the activity of two mechanisms: general and facultative thalamic pacemakers.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 6, pp. 570–574, November–December, 1977.     

GluR1 glutamate receptor subunit is regulated differentially in the primate basal ganglia following nigrostriatal dopamine denervation

Nigrostriatal dopaminergic denervation is associated with complex changes in the functional and neurochemical anatomy of the basal ganglia. The excitatory neurotransmitter glutamate mediates neural signaling at crucial points of this circuitry, and glutamate receptors are differentially distributed in the basal ganglia. Available evidence suggests that the glutamatergic corticostriatal and subthalamofugal pathways become overactive after nigrostriatal dopamine depletion. In this study, we have analyzed the regulation of the GluR1 subunit of the a-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor in the basal ganglia of primates following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopamine denervation. The dopamine denervation resulted in distinct alterations in GluR1 distribution: (1) GluR1 protein expression was markedly increased in caudate and putamen, and this was most pronounced in the striosomes; (2) GluR1 protein was altered minimally in subthalamic nucleus; (3) expression of GluR1 was down-regulated in the globus pallidus by 63% and in the substantia nigra by 57%. The down-regulation of GluR1 expression in the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata, may be a compensation for the overactive glutamatergic input from subthalamic nucleus, which arises after striatal dopamine denervation. Our results indicate that the glutamatergic system undergoes regulatory changes in response to altered basal ganglia activity in a primate model of Parkinson's disease. Targeted manipulation of the glutamatergic system may be a viable approach to the symptomatic treatment of Parkinson's disease.     

Alpha-MSH injected into the substantia nigra or intraventricularly alters behavior and the striatal dopaminergic activity

Rats were injected with 1 μg of alpha-melanocyte stimulating hormone (α-MSH) into the third ventricle and locally in the ventral tegmental area and in different regions of the substantia nigra. The modifications produced on grooming behavior and locomotion as well as on the dopamine content of the nucleus accumbens and the caudate putamen, were studied. Both intraventricular peptide administration and microinjections into the ventral tegmental area induced excessive grooming and a significant increase of the locomotor activity. The dopamine content of the nucleus accumbens and caudate putamen was markedly reduced. Injections of the peptide into the substantia nigra pars compacta failed to induce excessive grooming but did provoke a slight increase in locomotor activity and a smaller change in caudate dopamine content than that observed by injections in the ventral tegmental area or in the third ventricle. Dopamine levels in the nucleus accumbens were not changed. Finally, the injections of α-MSH into the lateral substantia nigra did not produce either biochemical or behavioral changes.The results suggests that α-MSH can modify, directly or indirectly, the striatal dopaminergic activity and that the behavioral alterations observed such as excessive grooming, could be mediated by the activation of the dopamine cells from the ventral tegmental area, that in turn may provoke a significative release of dopamine at the caudate putamen nucleus as well as in nucleus accumbens.     

The effect of electrical stimulation of vestibular-complex formations on systemic arterial pressure and regional blood flow

Electrical stimulation of the descending and medial vestibular nuclei produced increased arterial blood pressure and also changes in regional blood flow. On stimulation of the descending vestibular nucleus there was a decrease in blood flow in the hind-limb muscles, which might be a response to stimulation of the ventrolateral parts of the nucleus; when the central parts of the nucleus were stimulated the blood flow decreased both in the hind-limb muscles and in some of the viscera. Stimulation of the medial vestibular nucleus, particularly its ventral parts, caused a decrease in blood flow in the skin of the hind limbs, often accompanied by a decrease in visceral blood flow. On the basis of analysis of the afferent and efferent connections of the descending and medial vestibular nuclei, it is suggested that the cerebellum takes part in the transmission of vasomotor influences.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 35–42, January–February, 1970.