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At least 19 recordsLinked to original sources
PubMed1976

Ultrastructure of the Gunn rat substantia nigra I. Cytoplasmic changes.

The substantia nigra of various aged hyperbilirubinemic (Gunn) rats was studied by means of electron microscopy. The cytological features observed in the neuronal somata were the presence of (1) complex membranous bodies (CMBs), (2) dilated cisternae of granular endoplasmic reticulum, (3) single membrane bound vacuoles and (4) enlarged mitochondria. Nearly every neuronal soma studied in two week old Gunn rats contained CMBs, which consisted of several layers of membrane that usually, but not always surrounded small islands of cytoplasm. On occasion CMBs were seen to be directly connected with granular endoplasmic reticulum and, in a few instances, they were located within a cistern of endoplasmic reticulum. There were significantly fewer CMBs in the neuronal somata of adult Gunn rats. They were located peripherally in the somata or in the proximal portions of dendrites. Furthermore, in these animals the cytoplasm appeared normal and did not exhibit the features commonly seen in younger animals. Only a few hyperchromatic neurons were observed and no pronounced gliosis was evident. Therefore it is assumed that the majority of substantia nigra neurons recovered from the toxic effect of bilirubin or that the concentration of bilirubin deposited in the substantia nigra is not sufficient to be lethal. The hypothesis that is considered is that CMBs represent autophagic activity which results from exposure of neurons to bilirubin. The adjacent neurites and glia did not demonstrate the cytoplasmic changes that were characteristic of the neuronal somata.

Age Factors↗
PubMed1975

Topographical study of the distribution of gamma-aminobutyric acid (GABA) in the human substantia nigra. A case study.

The topographical distribution of gamma-aminobutyric acid (GABA) in the substantia nigra of a 28-year-old male 4 h after death was investigated. In a preliminary study the entire substantia nigra was dissected from transverse sections. The results showed that there was no correlation between the GABA concentration and the number of melanin-rich nigral cell bodies. This was especially so in the rostral third of the substantia nigra. Using the method of Miyata and Otsuka, transverse sections (150 mum) of the rostral, middle and caudal substantia nigra were cut into 500 mum X 500 mum square blocks which were assayed for GABA by an enzymatic method. In the rostral substantia nigra the GABA distribution was markedly uneven. The highest concentration of GABA was found in the pars reticulata. Within the pars reticulata the highest levels of GABA clearly occurred in two separate regions, a medial and a lateral. In the middle and caudal substantia nigra the GABA distribution was again uneven; however, the highest GABA levels were divided between the pars reticulata and the pars compacta. The results support the view that in the substantia nigra the greatest part of the GABA content is due to the presence of striato-nigral nerve terminals which are known to synapse with the dendrites of the substantia nigra dopamine neurons. In the rostral substantia nigra the concentration of GABA within the pars reticulata is in keeping with the presence of dendrites of such neurons in this region. Presumably on this basis it can be assumed that in the middle and caudal substantia nigra the dendrites are oriented in a more rostro-caudal direction.

Adult↗
PubMed1976

Caudate stimulation and substantia nigra activity in the rat.

1. The responses of spontaneously active single neurones in the substantia nigra and overlying mesencephalic reticular formation have been analysed during the electrical stimulation of the ipsilateral caudate nucleus. Experiments were performed in rats anaesthetized with urethane or pentobarbitone. All recordings were made extracellularly with multi-barrelled glass micropipettes which were also used to test neuronal responsiveness to electrophoretically administered substances. The micropipette tip position was marked and the distribution of neurones studied has been analysed. 2. Single shock stimulation of the caudate nucleus inhibited neuronal activity in the substantia nigra (270/320 cells: mean latency 5-4 msec) and in the mesencephalic reticular formation (62/72 cells: mean latency 16-6 msec). However, these effects were often accompanied by periods of excitation. In pentobarbitone anaesthetized animals the latency and duration of these substantia nigra inhibitions was increased. 3. Compared with the zona reticulata, fewer neurones in the zona compacta of the substantia nigra responded to caudate stimulation in both urethane or pentobarbitone anaesthetized animals. 4. The activity of most cells was depressed by electrophoretically administered GABA or glycine and increased by acetylcholine or glutamate. Neurones of the mesencephalic reticular formation were less sensitive to GABA and glycine than substantia nigra neurones. Within the substantia nigra, both zona compacta and zona reticulata neurones were more sensitive to GABA than to glycine. Over-all, glutamate was a more potent excitant than acetylcholine (ACh). 5. Electrophoretic bicuculline methochloride (BMC) consistently reduced GABA but not glycine depression of substantia nigra neurones. Approximately twice as much BMC was required to reduce the endogenous inhibition of the same substantia nigra neurones and the amplitude of concomitantly evoked positive field potential as was required to abolish exogenous GABA responses. Some evoked substantia nigra inhibitions were resistant to BMC. 6. Electrophoretic strychnine consistently reduced glycine but not GABA depression of substantia nigra neurones, and did not modify caudate evoked inhibition of these neurones or the accompanying field potential. 7. The results support the concept of a slowly conducting caudato-nigral pathway which has both facilitatory and inhibitory components. The inhibitory pathway uses GABA as the neurotransmitter. The identity of the possible excitatory transmitter is unknown. The monosynaptic nature of this pathway is uncertain and the possible contribution of other bicuculline insensitive nigral inhibitory processes is discussed.

Action Potentials↗
PubMed1979

Efferent connexions of the pars lateralis of the substantia nigra (SNL).

Unilateral lesions were made in the lateral nucleus of the substantia nigra in eight cats and in the zona compacta and reticularis in two cats. After a 10 days survival period, brains were perfused and stored in 10% formalin. Frozen sections were stained with the De Olmos-Ingram and Fink-Heimer silver methods for degenerating axons and terminals. Efferents from the lateral nucleus of the substantia nigra projected to the dorsolateral third of the head of the caudate nucleus, putamen, medial reticular formation, central tegmental tract, amygdala, zona compacta and reticularis of the substantia nigra, ventral anterior and ventral ateral thalamic nuclei. Projections to the amygdala, medial reticular formation and central tegmental tract were seen only in animals with lesions in the lateral nucleus of the substantia nigra. Projections to the caudate and putamen were more abundant when compared to those in the thalamus. Within the thalamus, projections to the ventral lateral nucleus were scanty compared to those in the ventral anterior nucleus. The present study compares for the first time efferent connexions of the lateral nucleus of the substantia nigra and those of the pars compacta and reticularis. The findings suggest a specialization of the different zones of the substantia nigra with regard to their projection sites.

Amygdala↗
PubMed1979

Tetanus toxin and synaptic inhibition in the substantia nigra and striatum of the rat.

1. The effects of tetanus toxin were determined on GABA-mediated synaptic inhibition of substantia nigra neurones evoked by striatal stimulation and on the presumed dopamine- and 5-hydroxytryptamine-mediated synaptic inhibition of striatal neurones evoked by nigral and dorsal raphe nucleus stimulation, respectively, in the urethane-anaesthetized rat. 2. Following an intranigral injection of tetanus toxin, striatal-evoked inhibition of substantia nigra neurones, which is sensitive to bicuculline, was rapidly abolished. This effect was not accompanied by any significant change in the responses of nigral neurones to ionophoretically administered GABA or other putative neurotransmitters and thus indicates a presynaptic site of action of the toxin. 3. The rate of onset of action of the toxin in the substantia nigra was extremely rapid (1-4 min) and appeared to be related to the rate of activation of the inhibitory pathway. 4. Injections into the substantia nigra of tetanus toxin neutralized with antitoxin had no significant effect on striatal-evoked inhibition in the substantia nigra. 5. Injections of tetanus toxin into the striatum failed to influence the inhibition of striatal neurones evoked by stimulation of the ipsilateral substantia nigra or the dorsal raphe nucleus, suggesting that tetanus toxin does not impair monoamine-mediated inhibition in the central nervous system. 6. Synaptic excitation which preceded substantia-nigra-evoked inhibition in striatal neurones and which occasionally preceded striatal-evoked inhibition in nigral neurones was also unaffected by tetanus toxin. 7. It is suggested that tetanus toxin selectively abolishes GABA-mediated synaptic inhibition in the central nervous system and may be a useful tool in the identification of such synaptic inhibitory mechanisms.

Action Potentials↗
PubMed1978

Biochemical changes accompanying unilateral 6-hydroxydopamine lesions in the rat substantia nigra.

The biochemical consequences of a unilateral 6-hydroxydopamine injection into the substantia nigra of the rat brain were investigated. Projections of dopaminergic neurons from the A8-A9-A10 regions to a number of forebrain areas were confirmed. No innervation to the hypothalamus, including the median eminence, or to the brain stem, could be found with the present techniques. No destruction of serotonergic or GABAergic fibers could be demonstrated in the lesioned substantia nigra. Increases in glutamic acid decarboxylase activity were found restricted to the caudate and zona compacta of the substantia nigra ipsilateral to the lesion, indicating the possibility of a physiological interaction between GABAergic and dopaminergic systems. The neuroanatomical localization of the nigral dopamine-sensitive adenylate cyclase was also studied. No change in enzyme activity was found after destruction of a great proportion of the dopaminergic cells, suggesting that this enzyme has an extradopaminergic localization in the substantia nigra.

Adenylyl Cyclases↗
PubMed1979

The effects of ageing on the pigmented nerve cells of the human locus caeruleous and substantia nigra.

The nucleolar volume and melanin content of the human locus caeruleus and substantia nigra has been measured in 70 persons of age range new born to 91 years, all of whom were at death free from overt neurological illness. Both cell types show a reduction in nucleolar size with advancing age, which becomes disproportionately larger towards old age. At 90 years of age, the change in nucleolar volume in cells of the locus caeruleus amounts to about 5% whereas cells of the substantia nigra show a loss of 20%. The greater decrease in nucleolar volume in cells of the substantia nigra is attributed to the higher concentration of melanin pigment occurring in these cells at old age, rather than the absolute amount present. This marked decline in nucleolar volume in cells of substantia nigra indicates a reduced activity in the cell which, in turn, may be reflected in the difficulty in control and coordination in muscular activity commonly seen in normal elderly persons.

Adolescent↗
PubMed1979

The organization of the efferent projections of the substantia nigra in the rat. A retrograde fluorescent double labeling study.

The organization of three of the efferent projections of substantia nigra has been investigated in rat by means of combined injections of two fluorescent retrograde tracers: red fluorescent Evans Blue and blue fluorescent DAPI-primuline mixture. First the distributions of the retrogradely labeled neurons in substantia nigra after injections of each of the two tracers in the striatum, thalamus and superior colliculus were compared with the distributions of the retrogradely labeled nigral neurons after HRP injections in these same structures. The findings in these sets of experiments were the same. This indicates that the two fluorescent retrograde tracers are as effective as HRP in tracing the efferent fiber connections of the substantia nigra. Subsequently the retrograde labeling of the substantia nigra neurons was studied after combined injections of the two fluorescent retrograde tracers in two of the above structures, in different combinations. In these experiments both single labeled neurons fluorescing either red or blue, as well as double labeled neurons fluorescing both red and blue were found. Double labeled neurons were present only in pars reticulata and occurred only after injections of the two tracers in thalamus and superior colliculus respectively. From this it has been concluded that in rat the various efferent projections from the substantia nigra are mainly derived from different neurons, but that at least part of the neurons which distribute fibers to superior colliculus also distributes collaterals to the thalamus.

Animals↗
PubMed1977

Dopamine-sensitive adenylate cyclase: location in substantia nigra.

A dopamine-sensitive adenylate cyclase with characteristics similar to those measured in the striatum is present in the rat substantia nigra. Destruction of dopamine cell bodies by intranigral 6-hydroxydopamine application failed to abolish the response of nigral adenylate cyclase to dopamine. In contrast, brain hemitransection between the striatum and substantia nigra, or a more circumscribed lesion of striatonigral pathways, abolished the dopamine stimulation of adenylate cyclase in the substantia nigra. These results suggest that dopamine receptors within the substantia nigra are not located on dopamine cell bodies but are associated with a pathway, containing gamma-aminobutyric acid or substance P, which projects from forebrain structures to the substantia nigra.

Adenylyl Cyclases↗
PubMed1976

Ultrastructure of the Gunn rat substantia nigra. II. Mitochondrial changes.

The substantia nigra of hyperbilirubinemic (Gunn) rats was studied using light and electron microscopic techniques. PAS-positive inclusions were observed within the neuronal somata of animals 2 to 12 weeks old. Incubation of tissue sections in 0.5% diastase inhibited most of the positive PAS reaction, thus indicating the intraneuronal presence of glycogen. Electron microscopic examination of the tissue substantiated the histochemical data. Mitochondria in neuronal somata contained collections of osmiophilic granules, 200-300 A diameter, in their intracristal (intermembrane) space. These granules were typical of beta-glycogen particles. In increasingly older animals (from 2 to 12 weeks old) progressively fewer collections of intramitochondrial glycogen were observed. In these same animals there was, however, a concomitant increase of osmiophilic granules, 400-600 A diameter, located in the cisternae of granular endoplasmic reticulum. These granules corresponded to alpha-glycogen. After 12 weeks of age, only occasional glycogen granules were seen in either the mitochondria or endoplasmic reticulum. It is suggested that the intramitochondrial glycogen represents an alternate means by which the neuron is able to manufacture ATP following the disruption of oxydative phosphorylation caused by bilirubin. Furthermore it is suggested that with the recovery of oxydative phosphorylation the intramitochondrial collections of glycogen are transferred to the endoplasmic reticulum where glycogenolysis might possibly occur.

Age Factors↗
PubMed1978

The dorsal and medial raphe projections to the substantia nigra in the rat: electrophysiological, biochemical and behavioural observations.

Electrophysiological experiments have been performed in urethane anaesthetized rats to investigate the projections from the dorsal (DRN) and medial raphe nuclei (MRN) to the substantia nigra. The biochemical and behavioural effects following discrete electrolytic lesions in the dorsal and medial raphe have also been investigated. Stimulation of the DRN produced predominantly inhibition of spontaneous activity of single neurones in the substantia nigra though some neurones were also excited. Bilateral stimulation of the substantia nigra produced antidromic spikes in DRN and MRN neurones. Lesions of the DRN and MRN produced a significant reduction in substantia nigra 5-HT concentration. Additionally, DRN lesions reduced striatal 5-HT, while MRN lesions reduced hippocampal 5-HT. Both lesions increased substantia nigra HVA concentration but did not affect DA concentration. Neither DRN nor MRN lesions affected striatal HVA, although DA levels were significantly elevated after 14 days. Animals with DRN lesions explored more than controls or MRN-lesioned animals. However, this behaviour was transient and was not observed after 14 days. On the other hand, MRN-lesioned animals were significantly hyperactive. These observations suggest that the substantia nigra receives a direct monosynaptic inhibitory input from the DRN and MRN and that these pathways use 5-HT as a neurotransmitter serving to tonically inhibit dopaminergic neurones. While 5-HT and dopamine appear to be involved in the control of motor behaviour, the precise relationship between these serotoninergic and dopaminergic systems in this respect is unclear.

Animals↗
PubMed1976

Comparison of effects of drugs on dopamine metabolism in the substantia nigra and the corpus striatum of rat brain.

The influence of apomorphine, chloral hydrate, haloperidol, morphine, oxotremorine, pargyline, probenecid and promethazine on DOPAC and HVA levels was studied in the substantia nigra (including the ventral tegmental dopaminergic regions) and corpus striatum of the rat brain. The time--effect curves of changes in HVA levels after pretreatment with apomorphine, haloperidol, morphine, oxotremorine or promethazine are presented. The time--effect curves for the substantia nigra showed an initial rapid HVA rise, which was not observed in the corpus striatum. Promethazine treatment caused a small but significant HVA rise in the substantia nigra only. Chloral hydrate, morphine and oxotremorine induced a similar percentage increase in DOPAC and HVA levels in the substantia nigra as well as in the corpus striatum. Haloperidol, however, caused a small percentage change in the metabolite levels in the substantia nigra when compared to the pronounced rise seen in the corpus striatum. The apomorphine-induced HVA decrease observed in both structures provides evidence for the presence of a dopaminergic receptor in the substantia nigra.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1977

Activity of neurons in the region of the substantia nigra during feeding in the monkey.

The activity of single neurons in the region of the substantia nigra of the monkey was recorded during feeding to investigate their function in ingestive behavior. It was observed that some neurons in the substantia nigra and the adjacent tegmentum altered their activity during feeding, in relation to mouth movements. The activity of these neurons was related to mouth movements in that the responses of the units were similar when the monkeys drank fluids with different tastes as long as the same movements were made, in that equally good responses could be obtained when the monkey moved his mouth to non-food objects, and in that in some units opposite responses were obtained when ipsilateral as compared with contralateral mouth movements were made. It was also shown that the responses of these units associated with mouth movements were similar when the monkeys were hungry and when they were satiated. These findings suggest that the activity of some neurons in the region of the substantia nigra is related to the execution of movements which may be involved in feeding, and that the activity of these neurons is not related to the initiation of feeding. Self-stimulation through the recording microelectrodes could be obtained just dorsal to the substantia nigra, but the neural basis of this self-stimulation is not known.

Action Potentials↗
PubMed1979

Turning behaviour induced by injection of muscimol or picrotoxin into the substantia nigra demonstrates dual GABA components.

Injection of the GABA agonist muscimol into rat caudal substantia nigra caused contralateral turning, whereas injection into the rostral substantia nigra caused ipsilateral turning. The GABA antagonist picrotoxin had the opposite effect. These findings support the hypothesis that GABA has dual actions in the substantia nigra. Ipsilateral turning induced by injection of muscimol into rostral nigra was abolished by haloperidol pretreatment, indicating the involvement of dopaminergic mechanisms. Haloperidol pre-treatment did not prevent turning induced by muscimol injected into the caudal nigra, supporting the existence of a non-dopaminergic nigral output system.

Animals↗
PubMed1976

Evidence for the existence of a raphe projection to the substantia nigra in rat.

The effect of electrical stimulation of the median raphe nucleus on the activity of spontaneously firing single neurones in the substantia nigra and mesencephalic reticular formation (MRF) has been investigated in urethane anaesthetized rats. Depression of activity was the predominant effect observed although this was sometimes accompanied by periods of excitation. Some neurones were only excited. The latency of inhibition of substantia nigra neurones was constant whereas that of MRF neurones was more variable. Microiontophoretically applied 5-hydroxy-tryptamine (5-HT) and dopamine (DA) produced mainly inhibition of neuronal activity, but excitation and biphasic effects were also seen. There was a good correlation between the direction of neuronal responses in the substantia nigra to median raphe stimulation and to the effects of 5-HT but not DA. Discrete electrolytic lesions of the median raphe nucleus were followed by a decrease in 5-HT but not GABA concentrations in the substantia nigra. In addition striatal 5-HT, GABA and NA concentrations were unchanged whereas striatal DA was increased. These observations strongly suggest that the substantia nigra receives a direct inhibitory input from the median raphe nucleus and this pathway uses a 5-HT-like neurotransmitter. This pathway probably contributes to the regulation of nigrostriatal dopaminergic transmission.

Animals↗
PubMed1975

Dopamine-containing neurons of the substantia nigra and their terminals in the neostriatum.

Tne ultrastructural and fluorescence histochemical characteristics of the mature rabbit substantia nigra and neostriatum have been reviewed as a frame of reference for the developmental study. Biochemical investigations were reported on neostriatal dopamine concentrations and the relative uptake and accumulation of 3H-dopamine by this tissue from fetal to adult stages, to provide quantitative data for correlation with the fluorexcence information. The development of the neurons of the substantia nigra and their axons which project to the neostriatum has been presented from their appearance at day 14 of gestation to their maturation in early postnatal life. The initial bipolar neuroblasts, which develop in the midline of the caudal mesencephalon, are fluorescent as soon as they emerge from the ependymal zone. Their fluorescent axons, which form the nigroneostriatal pathway, reach the telencephalon at day 16 of gestation and ramify extensively in the putamen by day 20, but do not enter the caudate nucleus until several days later. Some of the early fluorescent axonal profiles in the putamen are extremely large. Electron microscopic study of theis stage suggests that the large fluorescent profiles may correspond to axonal growth cones or early synapses. A distinct substantia nigra, pars compacta and reticulata, can be recognized by fluorescence microscopy by day 20 of gestation. Electron microscopy reveals that the young neurons are multipolar with numerous developing dendrites, some of which exhibit early synaptic junctions. The subsequent maturaition of these cells and the neuropil is described. The fluorescent axons of the substantia nigra grow into the putamen and caudate nucleus in a nonuniform manner forming fluorescent islands throughout the neostriatum in late fetal life. Occasionally, minute beaded fluorescent axons are found. These profiles might correspond to some of the axons with varicosities "en passage" revealed by electron microscopy. In an attempt to identify further the dopamine-containing axon, the ultratructure of adult neostriatum incubated in 5-hydroxydopamine was reported. Axonal varicosities "en passage" containing a dense "tag" in the vesicles were found. Most of the tagged boutons did not exhibit synaptic contacts. The possible significance of these finding s as related to dopamine secretion are discussed.

Animals↗
PubMed1978

Release of dopamine in both caudate nuclei and both substantia nigrae in response to unilateral stimulation of cerebellar nuclei in the cat.

The effects of unilateral focal electrical stimulation of the deep cerebellar nuclei on the activity of the nigrostriatal dopaminergic neurons on both sides of the brain were examined in halothane anaesthetized cats. For this purpose, push-pull cannulae were inserted into both caudate nuclei and both substantia nigrae, and the release of [3H] dopamine ([3H]DA) continuously formed from [3,5-3H]L-tyrosine was estimated in superfusates. The unilateral electrical stimulation of the right cerebellar dentate nucleus induced a long-lasting increase in the release of [3H]DA in the left caudate nucleus and a simultaneous decrease in the release of [3H]transmitter in the right caudate nucleus. These changes were associated with opposite fluctuations in the release of [3H]DA from the corresponding substantia nigrae. Thus, the electrical stimulation of the right dentate nucleus induced a pronounced decrease in the release of the [3H]-amine in the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral substantia nigra, whereas the release in the ipsilateral substantia nigra was simultaneously increased. In contrast, the unilateral electrical stimulation of the right cerebellar fastigial nucleus resulted only in an increased release of [3H]DA in the ipsilateral (right) caudate nucleus, associated with a decreased release of the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral (left) dopaminergic system was not significantly affected. These results support a direct functional interaction between the cerebellum and the basal ganglia. They also suggest that the release of DA from dopaminergic axonal terminals is inversely correlated to the extent of the transmitter release from dendrites.

Adrenergic Fibers↗