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.     

A histometrical study on the globus pallidus in Huntington''s disease

Adenosine is recognised as an important regulator of myocardial function and coronary vascular tone in the ischaemic myocardium. It is produced by the enzymatic dephosphorylation of 5'-AMP by 5'-nucleotidase and the hydrolysis of SAH by SAH-hydrolase. 5'-Nucleotidase is thought to contribute to adenosine production aside from the accumulation of 5'-AMP in the ischaemic myocardium, while the hydrolysis of SAH plays a major role in adenosine production in the normoxic myocardium. 5'-Nucleotidase activity is reported to increase adenosine production through accumulation of ATP, ADP, H+, Mg2+ and inorganic phosphate during ischaemia. In addition, we have found that alpha 1 adrenergic receptors, activated in ischaemic hearts, increase both 5'-nucleotidase activity and adenosine production. Inactivation of adenosine deaminase and adenosine kinase may also contribute to adenosine production. On the other hand, the major role of endogenous adenosine is to increase coronary blood flow. This adenosine induced coronary vasodilatation is amplified by alpha 2 adrenoceptor stimulation. Adenosine induced vasodilatation is also enhanced by increasing H+ and opening ATP sensitive K+ channels, which occurs in the ischaemic myocardium. However, coronary vasodilatation is not the only effect of adenosine in the ischaemic myocardium. Stimulation of adenosine A2 receptors coupled to Gs proteins attenuates both free radical generation by activated leucocytes and aggregation of platelets. Adenosine A1 receptor activation coupled to G(i) proteins attenuates beta adrenoceptor mediated increases in myocardial contractility, Ca2+ influx into myocytes, and noradrenaline release from the presynaptic nerves. Any or all of these effects may attenuate ischaemic and reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

The behavioural effects of manipulating GABA function in the globus pallidus

Effects of drugs on precapillary vessels and oxygen uptake may differ from effects on resistance vessels and total flow in skeletal muscle. This study was performed to compare effects of phentolamine and isoproterenol, two drugs which are used to treat shock, on oxygen uptake in skeletal muscle. Oxygen uptake of gracilis muscle (GVO2) was measured in muscles perfused at constant flow or constant pressure in normotensive dogs. We compared effects of the drugs on oxygen uptake at doses chosen so that both drugs produced comparable effects on vascular resistance. With flow constant, phentolamine increased but isoproterenol decreased or did not alter GVO2. With constant pressure, phentolamine produced significantly greater increases in GVO2. For example, increases in GVO2 occurred with all three doses of phentolamine, but only with the high dose of isoproterenol. Neither drug altered oxygen-hemoglobin affinity of red blood cells or oxygen consumption of skeletal muscle in vitro. The results suggest that phentolamine produces more favorable effects than isoproterenol on oxygen uptake in skeletal muscle, presumably because of greater dilator action on precapillary sphincters.     

Dynamics of tremor-related oscillations in the human globus pallidus: a single case study

Physiological evidence indicates that the resting tremor of Parkinson's disease originates in oscillatory neural activity in the forebrain, but it is unknown whether that activity is globally synchronized or consists of parallel, independently oscillating circuits. In the present study, we used dual microelectrodes to record tremor-related neuronal activity from eight sites in the internal segment of the globus pallidus (GPi) from an awake Parkinson's disease patient undergoing stereotaxic pallidotomy. We utilized spectral analysis to evaluate the temporal correlations between multiunit activity at spatially separated sites and between neural and limb electromyographic activity. We observed that some GPi neural pairs oscillated synchronously at the tremor frequency, whereas other neural pairs oscillated independently. Additionally, we found that GPi tremor-related activity at a given site could fluctuate between states of synchronization and independence with respect to upper limb tremor. Consistent with this finding, some paired recording sites within GPi showed periods of transient synchronization. These observations support the hypothesis of independent tremor-generating circuits whose coupling can fluctuate over time.     

Disturbances of the rat motor activity during multiple microinjections of picrotoxin into the globus pallidus and caudal neostriatum

RNA-localization mechanisms involve specific sequences in the localized RNA and proteins that bind to these sequences and mediate the interaction with cytoskeletal elements. Until recently, it seemed as though two separate types of mechanisms were operating for mRNA localization--involving interaction with either microtubules or actin microfilaments. However, it is now clear that some of the protein components involved in mRNA localization can participate in both microtubule- and actin-dependent localization pathways. This, combined with new evidence for evolutionary conservation of some of these proteins, suggests a previously unanticipated uniformity in mRNA-localization mechanisms.     

Left-right differences in motor thresholds after stimulation of the globus pallidus before pallidotomy

A family is presented in whom hereditary angioedema (HAE) and hereditary breast cancer were coexistent, an association not previously reported. A potential for genetic and treatment-related interactions between the two conditions exists. The use of the hormonal agent danazol to suppress HAE is unlikely to adversely affect the development or outcome of breast cancer. Surgery, chemotherapy, and radiotherapy were received by affected family members, without triggering edema. Whether hormonal breast cancer treatment affects the suppression of HAE by danazol remains unknown.     

Emotional and motivational changes after bilateral lesions of the globus pallidus.

This study investigated motivational changes in a 44 year-old man (PJ) who developed considerable reduction in spontaneous activity and speech, flat affect, social withdrawal, loss of interest, inability to "feel," and lack of concern regarding his medical condition after bilateral, focal, anoxic lesions of the globus pallidus. PJ and 30 male controls performed a task designed to parse hedonic evaluation, or liking, from incentive motivation, or wanting. Affective stimuli were presented on a computer screen and subjects controlled viewing time by pressing keys. PJ's liking and wanting of unpleasant stimuli was similar to that of controls. In response to pleasant stimuli, PJ showed normal ratings of wanting and hedonic appreciation, but significantly reduced viewing time or made no responses. Active withdrawal from liked stimuli could constitute the basic mechanism underlying poor motivation and social withdrawal associated with globus pallidus damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Manganese poisoning reduces strychnine-insensitive glycine binding sites in the globus pallidus of the mouse brain

Manganese (Mn) poisoning is characterized by central nervous system manifestations, including psychiatric disturbances and extrapyramidal disorders. This metal is thought to produce neuronal degeneration due to cytotoxic products originated by oxidative stress and through an indirect excitotoxic process. In previous studies, we have found a reduction in the density of N-methyl-D-aspartate (NMDA) recognition sites in some brain areas of Mn-treated mice. Due to the close relationship between NMDA sites and strychnine-insensitive glycine (Gly) modulatory sites in the NMDA receptor complex, the [3H]-glycine ([3H]-Gly) binding was analyzed by autoradiographic methods in the brain of mice treated with manganese chloride for 8 weeks. Among all analyzed areas, only the globus pallidus showed a significant reduction in [3H]-Gly binding (27-28%). The Gly binding decrease, focalized in the globus pallidus, could reflect a degeneration of structures containing strychnine-insensitive Gly receptors, since this area is the most frequently reported damaged brain region in Mn intoxication. However, it might also be due to a Gly receptor down-regulation to control NMDA complex activation during Mn poisoning.     

Selective expression of a glutathione S-transferase subclass during spermatogenesis

Levels of the hGSTM3 glutathione S-transferase (GST) subunit in testis of the human fetus and infant were found to be only a small fraction of those in adults. To understand these observations and to determine whether hGSTM3 subunit expression is developmentally and/or hormonally regulated, an experimental model based on the rat testis homologue (subunit rGSTM5) was used. For prepubertal rats, testicular rGSTM5 subunit levels were very low, but a sharp increase was observed between weeks 6 and 7 of development, when testicular growth includes increased numbers of germ cells associated with spermatogenesis. In adult hypophysectomized rats, the rGSTM5 subunit content of testis decreased progressively over 5 weeks, at which time the subunit was barely detectable. In contrast, the other GST subunit types did not vary significantly during development or after hypophysectomy. These results suggest that rGSTM5 subunits in rat testis could originate from spermatogenic cells. Accordingly, GSTs were purified from human sperm, and it was shown that the hGSTM3 subunit was, by a large measure, the predominant form. These data are consistent with the notion that the differential expression of hGSTM3 during human testicular development can also be explained on the basis of its preferential location in germs cells.     

Effect of switching off the globus pallidus on alimentary and electrophysiologic responses induced by stimulation of the hypothalamus]

In chronic experiments on eight cats a direct electrical stimulation of the lateral hypothalamus evoked: 1) food eating in a state of satiation and 2) a reproduction of a conditioned food-procuring reflex, preliminarily elaborated to an acoustic signal. Bilateral electrolytic ablation of the globus pallidum abolished both reactions, but for different time periods. The first one was restored spontaneously on the 20th to the 46th day; the second disappeared for 2.5 to 8.5 months without spontaneous restoration. Stimulation of the lateral hypothalamus alimentary zones brought about a statistically significant rise of the thresholds of desynchronization reactions in the ipsi- and contralateral sensorimotor cortex. The activating role of the globus pallidum in the organization of a motivational alimentary excitation is discussed.     

Electrophysiological and Fos immunohistochemical evidence for the excitatory nature of the parafascicular projection to the globus pallidus

Extracellular recordings and immunohistological detection of c-Fos-like immunoreactive proteins were used to determine the synaptic effect of the parafascicular projection to the globus pallidus. Electrical stimulation of the parafascicular neurons induced a single-spike excitatory response with a stable latency of 2.3 ms, suggesting a monosynaptically driven effect. Pharmacological stimulation of the parafascicular nucleus with carbachol increased tonically the pallidal discharge rate by 142%. The discharge rate of the pallidal neurons was described by 37% in parafascicular-lesioned rats. These results demonstrate the excitatory nature and the tonic action of the parafasciculopallidal projection. Carbachol activation of parafascicular neurons also induced the synthesis of c-Fos-like immunoreactive proteins in the pallidal neurons. Control experiments in subthalamic-lesioned rats showed that the parafascicular excitation of the pallidal neurons remained, but both electrophysiological and expression of c-Fos-like immunoreactive proteins were attenuated. This suggests that the direct parafascicular excitation of the pallidal neurons is indirectly reinforced by the previously described parafascicular excitatory input to the subthalamic nucleus. Conversely, the effect of this last input to the subthalamic nucleus is dramatically enhanced in rats with pallidal lesion. Our results demonstrate the complex role of the parafascicular nucleus in activating both the globus pallidus and the subthalamic nucleus, two closely related structures. These results illustrate the integrative capacities of the globus pallidus, whose activity is modulated by multiple afferents.     

Simultaneous transplantation of fetal mesencephalic cells to the striatum and globus pallidus of rats with lesions induced by 6-hydroxydopamine

INTRODUCTION: Studies of neural transplants in experimental models of Parkinson's disease have concentrated their attention on ectopic transplants of foetal mesencephalic cells to denervated striatum. However, the external globus pallidus has recently been shown to play an important part in the physiopathology of this disease. OBJECTIVE: Bearing in mind the importance of loss of extra-striatal dopamine in the genesis of the clinical signs found in parkinsonism, the objective of this study was to evaluate the effect of foetal mesencephalic transplantation to the globus pallidus of hemiparkinsonian rats. MATERIAL AND METHODS: Following conventional transplantation methodolgy, suspensions of cells from the ventral mesencephalum of rat embryos (E-14) were implanted. The tissue was grafted into the striatum, pallidum-striatum and pallidum areas of rats with unilateral lesions of the striatonigral bundle. One, two, three and six months after transplantation, the rotatory activity induced by D-amphetamine was evaluated. The rotatory behaviour induced by apomorphine was evaluated at three months. Motor ability of the front legs was evaluated in all experimental groups three months after transplantation using the 'ladder test'. RESULTS: In the experimental groups in which a transplant was made to the globus pallidus there was a significant reduction (p < 0.01) in rotatory activity induced by D-amphetamine and by apomorphine as compared with the non-transplanted groups. CONCLUSIONS: Transplants of foetal dopaminergic cells survive in the globus pallidus of hemiparkinsonian rats and can improve the rotational activity induced by dopaminergic agonists.     

High intensity in the globus pallidus on proton and T2-weighted MRI in a case of dentato-ruburo-pallido-luysian atrophy of myoclonus epilepsy type

Stool samples from 880 residents in an urban slum in Dhaka, Bangladesh, were collected on 3 occasions over one year, and examined for intestinal parasites. Information on many potential risk factors for infection was obtained by questionnaire from a respondent in each household studied. In a crude univariate analysis of the data, several of the factors were found to be significantly associated with Strongyloides stercoralis infection. Most of these factors were co-variate with one another, and with poverty generally. Using Mantel-Haenszel chi 2 tests to control for confounding effects of each variable individually, the following 4 factors remained independently associated with S. stercoralis infection: respondent's use of a community latrine rather than a private latrine, living in a house with an earth floor rather than a cement floor, being of Bihari ethnicity, and being 7-10 years of age. Implications of these results for the epidemiology and control of strongyloidiasis are briefly discussed.     

Synaptic effects of identified interneurons innervating both interneurons and pyramidal cells in the rat hippocampus

GABAergic interneurons sculpt the activity of principal cells and are themselves governed by GABAergic inputs. To determine directly some of the sources and mechanisms of this GABAergic innervation, we have used dual intracellular recordings with biocytin-filled microelectrodes and investigated synaptic interactions between pairs of interneurons in area CA1 of the adult rat hippocampus. Of four synaptically-coupled interneuron-to-interneuron cell pairs, three presynaptic cells were identified as basket cells, preferentially innervating somata and proximal dendrites of pyramidal cells, but one differing from the other two in the laminar distribution of its dendritic and axonal fields. The fourth presynaptic interneuron was located at the border between strata lacunosum moleculare and radiatum, with axon ramifying within stratum radiatum. Action potentials evoked in all four presynaptic interneurons were found to elicit fast hyperpolarizing inhibitory postsynaptic potentials (mean amplitude 0.35 +/- 0.10 mV at a membrane potential of -59 +/- 2.8 mV) in other simultaneously recorded interneurons (n=4). In addition, three of the presynaptic interneurons were also shown to produce similar postsynaptic responses in subsequently recorded pyramidal cells (n=4). Electron microscopic evaluation revealed one of the presynaptic basket cells to form 12 synaptic junctions with the perisomatic domain (seven somatic synapses and five synapses onto proximal dendritic shafts) of the postsynaptic interneuron in addition to innervating the same compartments of randomly-selected local pyramidal cells (50% somatic and 50% proximal dendritic synapses, n=12). In addition, light microscopic analysis also indicated autaptic self-innervation in basket (12 of 12) and bistratified cells (six of six). Electron microscopic investigation of one basket cell confirmed six autaptic junctions made by five of its boutons. Together, these data demonstrate that several distinct types of interneuron have divergent output to both principal cells and local interneurons of the same (basket cells) or different type. The fast synaptic effects, probably mediated by GABA in both postsynaptic interneurons and principal cells are similar. These additional sources of GABA identified here in the input to GABAergic cells could contribute to the differential temporal patterning of distinct GABAergic synaptic networks.     

Features of the spike activity of globus pallidus neurons and pallido-thalamic functional interactions during targeted verbally cued movements in humans

OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in women with various categories of family history. DESIGN: A meta-analysis of all published case-control and cohort studies. METHODS: Pooled relative risk estimates were calculated for the case control studies, using the Mantel-Haenzel method. These estimates were combined with the relative risks from the cohort studies. The pooled estimates of relative risk were used to estimate lifetime risks of ovarian cancer from age 15 up to age 75, for various categories of family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of developing ovarian cancer were calculated for the categories of women with 1. an affected first degree relative; 2. an affected mother; 3. an affected sister; and 4. women with more than one affected relative. RESULTS: The relative risk to first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this relative risk declines with age. The relative risk to mothers of cases 1.1 (95% CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1), and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a substantially higher risk of developing ovarian cancer compared with women without such a history. However the risk is small for most categories of family history, except for the small number of individuals who have more than one affected relative.     

Differential effects of unique profile antipsychotic drugs on extracellular amino acids in the ventral pallidum and globus pallidus of rats

The effects of antipsychotic drugs (APDs) on brain dopamine receptors in the striatum are ultimately expressed through efferent projections which primarily use amino acid transmitters, including gamma-aminobutyric acid and glutamate. The present study examined the effects of APDs on extracellular amino acid levels in the rat ventral pallidum (VP) and globus pallidus (GP), areas that receive projections from distinct striatal subregions. Clozapine, an APD with low motor side effect liability, and metoclopramide, a low-potency APD with high motor side effect liability, were compared with haloperidol, a widely used APD with high motor side effect liability. Drugs were administered subcutaneously and amino acid levels were monitored concurrently in the VP and GP by intracranial microdialysis. High doses of haloperidol and metoclopramide increased and clozapine decreased extracellular gamma-aminobutyric acid levels in the GP but not the VP. Low, but not high, doses of the three drugs tended to increase extracellular glutamate levels in both pallidal regions. Clozapine, but not the other two drugs, decreased extracellular threonine in the GP and glycine and threonine in the VP. Results indicate a correlation between increased gamma-aminobutyric acid levels in the GP and the propensity of the APDs tested to induce motor side effects. The novel effects of clozapine on extracellular glycine and threonine further distinguish this drug as a unique antipsychotic compound.     

Peptidergic innervation of the rat cornea

Corneal nerves regulate corneal epithelial integrity, proliferation, and wound healing. The mechanisms by which the nerves mediate their effects remain poorly understood; however, the release of biologically active neuropeptides has been hypothesized. The purpose of the current investigation was to determine the relative densities, distribution patterns, and origins of rat corneal nerves containing each of eight different neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), galanin (GAL), neuropeptide Y (NPY), methionine-enkephalin (M-ENK), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), and cholecystokinin (CCK). In the first set of experiments, immunohistochemical demonstrations of the above neuropeptides were performed on free-floating corneal sections cut tangential to the corneal surface. The results showed that six of the peptides, CGRP, SP, GAL, NPY, M-ENK, and VIP were present in rat corneal nerves. The innervation patterns of corneal nerves containing each of these six peptides were then documented by mapping all fibers in serial sections from select corneal quadrants onto a series of line drawings by using a drawing tube. In the second set of experiments, the origins of the corneal peptidergic nerve fibers were determined by selective ocular denervations. Unilateral combined sensory and sympathetic ocular denervations or unilateral sympathetic ocular denervations were performed in adult rats by transecting the ophthalmomaxillary nerve and/or removing the superior cervical ganglion. After 5-7 days, each of the ipsilateral corneas was sectioned and processed immunohistochemically for the presence of one of the six peptides found in experiment one, and the fibers that survived the ocular denervations were plotted onto line drawings. Ocular denervations revealed that corneal peptidergic nerves have sensory (CGRP, SP, and GAL), sympathetic (NPY), and parasympathetic (GAL, NPY, M-ENK, and VIP) origins. The results of this investigation have shown that the peptidergic innervation of the rat cornea is more extensive and complex than previously reported. This is the first investigation to show the presence of GAL in the rat cornea, and the first to demonstrate the presence of NPY-, VIP-, and M-ENK-IR nerve fibers in the cornea of any species.