Effects of substantia nigra and caudate nucleus lesions on avoidance learning in rats.

Compared to 21 operated and 14 nonoperated controls, 36 male Sprague-Dawley albino rats with small bilateral lesions in the anteroventral caudate nucleus or the rostral substantia nigra were significantly impaired in the acquisition of 1-way active avoidance, passive avoidance requiring the inhibition of the previously acquired 1-way response, and shuttle-box avoidance. Ss with nigral lesions took significantly more trials to criterion than Ss with caudate lesions on 1-way avoidance. Results are considered in terms of the intimate anatomical and neurochemical relationships between these structures, and a circuit of structures involved in avoidance learning is suggested. (34 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of entopeduncular nucleus and reticular part of substantia nigra on the antiepileptic activity of the caudate nucleus in the neocortex

Experiments carried out on rats show that inhibiting influences from striatal electrostimulation on the cortical epileptic activity are removed under conditions of destruction of entopeduncular nucleus (EPN). They decrease under conditions of lesion of substantia nigra pars retieulata (SNR). It is found that both EPN and SNR destruction resulted in antiepileptic effect on the development of the neocortex epileptic activity complexes. Possible mechanisms realizing inhibition of the caudate nucleus effects on the neocortex epileptic activity are discussed.     

Apoptosis in substantia nigra following developmental hypoxic-ischemic injury

We have previously observed that either hypoxic-ischemic or excitotoxic striatal injury during development is associated with a reduction in the adult number of dopaminergic neurons in the substantia nigra. This decrease occurs in the presence of preserved striatal dopaminergic markers and in the absence of direct nigral injury. We have also observed that natural cell death, with the morphology of apoptosis, occurs in the substantia nigra, and that there is an induced apoptotic cell death event following early striatal excitotoxic injury. We now report that forebrain hypoxic-ischemic injury is also associated with an induced cell death event in the substantia nigra, with both morphological and histochemical features of apoptosis. Induced apoptotic cell death occurs in immunohistochemically defined dopaminergic neurons. While the mechanisms for this induced cell death are not yet known, in the case of the pars compacta it may be related to the loss of normal striatal target-derived developmental support. Since dopaminergic neurons are postmitotic at the time of the injury, we conclude that this induced cell death is responsible for the diminished adult number of dopaminergic neurons. We also conclude that hypoxic-ischemic injury to the developing brain in general causes not only direct, necrotic injury to vulnerable regions, but also induced apoptotic death at remote sites. The significance of this finding is that apoptosis is a distinct death mechanism, with unique regulatory pathways, which can potentially be modified by approaches different from those which might influence cell death in regions of direct injury. In view of the present finding that apoptosis can occur in the setting of hypoxic-ischemic injury, and our previous work demonstrating its occurrence following excitotoxic injury, it seems likely that it may occur following other forms of injury to the immature brain in which excitotoxic injury plays a role, such as seizures, head trauma and hypoglycemia.     

Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat

The organization of the major efferents of the rat subthalamic nucleus (STN) was investigated using a fluorescent retrograde double-labeling technique. Red fluorescent Evans Blue was injected into the globus pallidus and blue fluorescent DAPI-Primuline was injected into the substantia nigra. After retrograde axonal transport many double-labeled neurons were seen throughout the STN. Occasionaly double-labeled cells were seen in the lateral hypothalamus just medial to the STN and in a thin lateral strip of neurons extending laterally from the STN. Evidence for a mediolateral topography in both the STN-pallidal and STN-nigral pathways was obtained. The STN contains few, if any, local interneurons. Cell counts revealed that at least 94% of, and possibly all, STN neurons send axon collaterals to both the globus pallidus and substantia nigra.     

Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat

The effect of cannabinoids on the excitatory input to the substantia nigra reticulata (SNr) from the subthalamic nucleus was explored. For this purpose a knife cut was performed rostral to the subthalamic nucleus to isolate the subthalamic nucleus and the SNr from the striatum, a major source of cannabinoid receptors to the SNr. The data showed that the cannabinoid agonist WIN55,212-2 blocked the increase in the firing rate of SNr neurons induced by stimulation of the subthalamic nucleus with bicuculline. Furthermore, the cannabinoid antagonist SR141716A antagonized the effect of the cannabinoid agonist. This study showed that cannabinoids regulate not only the striatonigral pathway, as previously reported, but also the subthalamonigral pathway. The opposite influences of these two inputs to the SNr, inhibitory and excitatory respectively, suggest that endogenous cannabinoids play a major role in the physiological regulation of the SNr.     

GABA and glutamate levels in the substantia nigra reticulata following repetitive cerebral ischemia in gerbils

Repetitive cerebral ischemia produces more severe damage than a similar single duration insult. We have previously shown that, in gerbils, damage in the substantia nigra reticulata (SNr) is seen with repetitive insults rather than a single insult. We have also shown that there is a progressive decrease in the extracellular GABA in the striatum in the days preceding such damage, speculating that a loss of GABA may be in part responsible for this damage. This study evaluates the GABA levels in the SNr in animals exposed to repetitive ischemic insults. Each animal received a total of three ischemic insults of 3-min duration at hourly intervals. In vivo microdialysis was carried out to analyze the GABA and glutamate dialysate levels on Days 1, 3, 5, 7, and 14 following the ischemic insult. In the control and treated (ischemic) animals, there was a significant increase in the GABA levels with the introduction of nipecotic acid on Days 1, 3, 5, and 14. However, on Day 7 there was a significant attenuation in the GABA response to nipecotic acid in the treated animals in comparison to the controls. The glutamate levels in the treated animals were similar to the control animals on Days 1, 3, 5, and 7. However, on Day 14 the glutamate levels were significantly lower than on previous days. Our experiments for the first time measure extracellular glutamate and GABA responses in the SNr in animals exposed to repetitive ischemic insults. Our experiments show that there is a significant decrease in the GABA concentrations at a time when ischemic damage is developing in this region. This confirms our hypothesis that a decrease in GABA may be one factor contributing to neuronal damage during the period following repetitive ischemic insults. Further, the rebound increase in GABA levels on Day 14 with a concomitant fall in glutamate levels would indicate that reparative processes are still active in the 2 weeks following the insult.     

Ultrastructure of developing substantia nigra in humans

Electron microscopy of the maturing neurons and developing and maturing synapses in the substantia nigra of 14 human embryos/foetuses of 8-24 weeks of gestation are reported. At 8 weeks, cells were immature with very little cytoplasm and cellular organelles. Contact sites of processes appeared more electron dense than the other areas. At 12 weeks, many of the cells had acquired more cytoplasm and cellular organelles and could be identified as neurons. Asymmetric synapses with clear, round synaptic vesicles also were identifiable at this age. Such synapses, first to appear in the developing substantia nigra, are reported to be formed by recurrent collateral nigro-striatal fibres. Substance P fibres from the striatum also are contributing to this type of synapse. At 15-16 weeks, not only was the number of such synapses increased, but many appeared morphologically mature. Symmetric synapses having clear round vesicles along with a few dense core vesicles also appeared at this stage, suggesting striatal input. By 24 weeks of gestation, most of the neurons had cytological features comparable to that of the mature neurons. There was an increase in the total number of synapses and the individual variety from 15 to 24 weeks of gestation. The present study indicates that synaptogenesis starts at 8 weeks and continues beyond 24 weeks of gestation.     

MRI of the occipital cortex, red nucleus, and substantia nigra during visual aura of migraine

PURPOSE: Although radical nephrectomy is the standard treatment for localized unilateral renal cell carcinoma with a normal contralateral kidney, there is ongoing interest in the use of nephron sparing surgery or partial nephrectomy in such cases. The extent of radical surgery in such cases has also been reconsidered in view of the uncertainty regarding the malignant or benign nature. MATERIALS AND METHODS: Of 14,793 autopsies in Jena from 1985 until 1995 there were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was 40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS: Grade 1 renal cell carcinomas decreased in frequency with increasing tumor diameter, while an opposite result was noted for grade 3. Lymph node and distant metastases were well correlated with tumor size. With an increase in tumor size the frequency of venous involvement increased as well. Significantly more multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40 mm. compared to those 20 mm. or less in diameter. CONCLUSIONS: The metastatic potential and biology of these small nodules are not yet known. To lower the risk of local recurrence the results of our study suggest that nephron sparing surgery might be advisable in patients with renal cell carcinoma 20 mm. or less in diameter.     

Site-specific effects of local pH changes in the substantia nigra pars reticulata on flurothyl-induced seizures

Local cerebral changes of acid-base balance may interfere with neuronal communication. Acidosis enhances and alkalosis suppresses GABAA receptor neurotransmission while there are opposite effects on NMDA receptor transmission. In this study, we determined site-specific effects of acidified solutions of Na-HEPES-artificial cerebrospinal fluid infused into the anterior or posterior area of the substantia nigra pars reticulata (SNR) in rats. Two levels of pH were compared: 6.7 and 7.4. Rats were challenged with flurothyl and the threshold for clonic and tonic-clonic seizures was determined. In the anterior SNR, there were no differences between the effects of the solution with pH 6.7 and 7.4 on flurothyl seizures. In contrast in the posterior SNR, microinfusions with pH 6.7 had proconvulsant effects. The results suggest that local pH changes may have site-specific effects on seizure susceptibility in vivo.     

Enhanced protein synthesis in the ipsilateral substantia nigra following middle cerebral artery occlusion in the rat

The purpose of this randomised single blinded study was to determine the optimal size of laryngeal mask airway in the normal adult population, to test the validity of the current selection criteria and to determine if any externally measured anatomical variable correlated with optimal size. In each of 30 apnoeic anaesthetised adults weighting less than 100 kg, size 3, 4 and 5 laryngeal mask airways were inserted in random order by a skilled user and the cuff inflated to a standard pressure (60 cm H2O). Optimal size was based on four criteria in order of priority: number of attempts at placement, oropharyngeal leak pressure, fiberoptic score and percentage of vocal cords seen. The size 5 laryngeal mask airway was optimal in 19/30 and the size 4 in 11/30. In no patient was the size 3 the optimal fit. Oropharyngeal leak pressure was significantly higher for each progressively large size and the fiberoptic view was significantly better for the size 4 and size 5. There was no significant predictive value in any externally measured anatomical variable, but height was the most useful. The best current selection strategy was to choose a size 5 for males and size 4 for females. Potentially useful new strategies may be to use the size 5 in all adults, or a size 5 > or = 165 cm in height and size 4 for < 165 cm. We conclude that predicting the optimal size of laryngeal mask airway for individual adult patients is complex. The best size selection strategies involve use of the size 4 and 5 laryngeal mask airways in adults.     

Striatal dopamine-glutamate interactions reflected in substantia nigra reticulata firing

To gain insight into the role of striatal dopamine in basal ganglia functioning, dopaminergic drugs alone and in combination with the glutamate receptor agonist kainic acid were infused in the lateral striatum via a microdialysis probe, while single-unit recordings of substantia nigra reticulata neurons were made in chloral hydrate-anaesthetized rats. Striatal infusion of dopaminergic drugs did not significantly affect the firing rate of substantia nigra reticulata neurons, which was related to the low activity of striatal cells under basal conditions, illustrated by the lack of effect of striatal infusion of TTX on substantia nigra reticulata activity. Under glutamate-stimulated conditions, striatal infusion of d-amphetamine potentiated the inhibition of substantia nigra reticulata neurons induced by striatal kainic acid. Thus, under stimulated but not basal conditions, the modulatory role of dopamine in the striatum could be demonstrated. Dopamine potentiated the inhibitory effect of striatal kainic acid on the firing rate of the basal ganglia output neurons.     

Sensitization and conditioning of feeding following multiple morphine microinjections into the nucleus accumbens

The effects of repeated morphine infusions (10 micrograms/0.5 microliter) into the nucleus accumbens on feeding were studied in sated rats. As shown previously, intra-accumbens morphine infusions induced a large increase in food intake. After undergoing repeated morphine treatment, animals consumed significant quantities of food in response to a saline or sham injection, compared to their pre-morphine baseline. This conditioned feeding was present up to 18 days after the final drug infusion. Additionally, repeated morphine administration caused a progressive sensitization of feeding; the final morphine infusion elicited nearly double the amount of food intake as the first. Multiple saline infusions had no behavioral effects. Repeated stimulation of opiate receptors may enhance associative mechanisms such that previously neutral environmental stimuli acquire the ability to elicit feeding. Abnormal activation of this system may be a possible neural substrate for compulsive feeding and bulimia.     

Inhibition of thalamic and hypothalamic somatosensory evoked potentials by stimulation of substantia nigra and its modification by morphine and methotrimeprazine (levomepromazine)

A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum medianum of the thalamus (CM) and posterior hypothalamic area (PHA) following sciatic stimulation in unanesthetized rabbits. The nigral inhibitory effect on CM was prolonged by the administration of morphine (4 mg/kg i.v.) but not influenced by that of methotrimeprazine (2-4 mg/kg i.v.). In contrast, the nigral inhibitory effect on PHA was enhanced by the injection of methotrimeprazine (2 mg/kg i.v.), but not changed by that of morphine (4 mg/kg i.v.). These results indicate that the inhibitory system originating from the substantia nigra operates on the somatosensory transmissions from the peripheral nerve to the thalamus and hypothalamus, and that morphine or methotrimeprazine in small doses induced a selective potentiation of the nigral inhibitory influence on the thalamus or hypothalamus, respectively.     

A stereological study of substantia nigra in young and old rhesus monkeys

The number of pigmented and non-pigmented neurons in the substantia nigra (SN) of 10 old and six young female Macaca mulatta monkeys and in three old alpha male monkeys were estimated using new stereological cell counting methods. No systematic right-left differences were noted, nor were old animals different from young ones with respect to SN volume (68.9 mm3 vs. 62.8 mm3) or absolute number of nerve cells (320,000 vs. 312,000). However, the total number of pigmented neurons was about eight times higher in old animals compared with young ones (166,000 vs. 21,400) while the total number of non-pigmented SN neurons was less than half in old animals compared with young ones (139,000 vs. 285,000). These differences create difficulties in generalizing experimental results from the rhesus animal model to man. It seems unlikely that a simple correlation can be made between pigmented and tyrosine hydroxylase (TH) positive neurons in SN in monkeys. Instead of estimating the total number of pigmented and non-pigmented cells, only SN neurons positive for TH using immunohistochemical techniques might be used an indicator of the total number of dopaminergic neurons in SN in monkeys.     

Functional coupling between substantia nigra and basal ganglia homologues in amphibians.

Neuroanatomical and pharmacological experiments support the existence of a homologue of the mammalian substantia nigra-basal ganglia circuit in the amphibian brain. Demarcation of borders between the striatum and pallidum in frogs, however, has been contentious, and direct evidence of functional coupling between the putative nigral and striatal homologues is lacking. To clarify basal ganglia function in anurans, the authors used expression of immediate-early gene egr-1 as a marker of neural activation in the basal ganglia of túngara frogs (Physalaemus pustulosus). Regional variation in egr-1 mRNA levels distinguished striatal and pallidal portions of the basal ganglia and supported the grouping of the striatopallidal transition zone with the dorsal pallidum. As further evidence for a functional coupling between the dopaminergic cells in the posterior tuberculum (the putative substantia nigra homologue) and the basal ganglia, a positive relationship was demonstrated between the size of the dopaminergic cell population and the neural activation levels within the dorsal pallidum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)