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[Biometrical fresh volume analysis of nucleus caudatus, putamen and globus pallidus in an ontogenic series of Tupaia belangeri].

The fresh volumes of the nucl. caudatus (including the nucl. accumbens septi), putamen, globus pallidus and of the whole brain of 37 male Tupaia belangeri aged between 36-536 days of ontogenesis have been determined. The growth of these nuclear regions is described by the logistic function. The parameters were approximated by means of an iterative procedure by the least square method. The "ideal" volume of the globus pallidus is 9,6 mm3, of the striatum 113 mm3, and of the whole brain 3 260 mm3. The degrees of maturity of globus pallidus, striatum and the whole brain do not differ significantly from each other concerning the date of birth (43th day of ontogenesis), the growth factors are about 5,5. The nucl. caudatus, including the nucl. accumbens septi, and the putamen demonstrate almost the same course in their degrees of maturity and growth dynamics within the tested age interval. In the course of postnatal development the globus pallidus grows more quickly than the whole brain, and the whole brain, on the other hand, more quickly than the striatum. The half value time of the globus pallidus is about 53 days of ontogenesis, of the whole brain about 56 days of ontogenesis and of the striatum about 58 days of ontogenesis. On the 70th day of ontogenesis, the difference between the degrees of maturity of globus pallidus (93 per cent) and striatum (= nucl. caudatus + nucl. accumbens septi + putamen) (72 per cent) is 21 percent. This complicated growth dynamics can be seen exactly by considering the non-linear logistic functions, the degrees of maturity, and the growth-rate of the degrees of maturity.

Age Factors↗

Striatal grafts in rats with unilateral neostriatal lesions--II. In vivo monitoring of GABA release in globus pallidus and substantia nigra.

GABA release was recorded in vivo by push-pull perfusion from the globus pallidus and substantia nigra of control rats, rats with unilateral ibotenic acid lesions of the neostriatum, and rats with embryonic striatal tissue grafts implanted in the lesioned striatum. The lesions reduced baseline levels of GABA release to 5% of control levels in the globus pallidus and to 13% of control levels in the substantia nigra pars reticulata. GABA release was substantially restored in both the globus pallidus and substantia nigra of the grafted rats, to 34 and 60%, respectively. Peripheral injection of the dopaminergic stimulant methamphetamine induced a short (lasting approximately 20 min) 4-5 fold increase in GABA release in the intact globus pallidus and a longer (lasting longer than 80 min) increase in the substantia nigra. The stimulatory effect of methamphetamine on GABA release was completely abolished in both sites by the strial lesions, suggesting that the effect was mediated via a direct or indirect dopaminergic action on striatal output neurons. The grafts reinstated methamphetamine-induced stimulation of GABA release in striatal output targets to a level (as a proportion of baseline) that was similar to that seen in the control rats. The results support the view that activation of the dopaminergic inputs to the striatum is functionally excitatory on the major striatal output projections to the globus pallidus and substantia nigra pars reticulata. The results also support the hypothesis that striatal grafts have the capacity to become functionally incorporated by reciprocal graft-host connections into the neural circuitry of the host brain.

Animals↗

Optimization of TI values in inversion-recovery MR sequences for the depiction of fine structures within gray and white matter: separation of globus pallidus interna and externa.

RATIONALE AND OBJECTIVES: The authors' purpose was to search the inversion time (TI) values that enable the best differentiation of fine structures in gray matter (gray-gray differentiation). MATERIALS AND METHODS: Seven healthy adult volunteers with no history of neurologic disease or head trauma were recruited and gave their informed consent. The subjects consisted of two men and five women ranging in age from 25 to 38 years, with a mean age of 28 years +/- 5. The subjects were imaged with a turbo spin-echo inversion-recovery sequence. This sequence was performed in the axial plane at the level of the basal ganglia with the following parameters: repetition time, 3,200 msec; echo time, 15 msec; three signals acquired; echo train, seven; section thickness, 3 mm; matrix size, 256 x 256; and field of view, 180 mm. The tested values were TI = 100, 200, 300, 400, and 500 msec. Region-of interest measurements were performed at the following anatomic structures and represent gray-gray and white-white differentiations, respectively: globus pallidus externa versus globus pallidus interna, and optic radiation versus surrounding white matter. RESULTS: The maximum contrast index value occurred at TI = 400 msec for globus pallidus externa versus globus pallidus interna (P < .05) With the contrast-to-noise ratio, no significant difference in gray-gray differentiation was observed among the various TIs. The minimum signal-to-noise ratio of the gray matter occurred at TI = 400 msec (P < .05). A subjective evaluation revealed an overall superiority of gray-matter differentiation with TI = 400 msec. CONCLUSION: A TI of 400 msec was the most suitable for this purpose.

Adult↗

Bursting properties of units in cat globus pallidus and entopeduncular nucleus: the effect of excitotoxic striatal lesions.

The bursting properties of units recorded in globus pallidus and entopeduncular nucleus were studied in awake cats sitting quietly before and after ipsilateral excitotoxic striatal lesions. A computerized statistical procedure was used to identify and evaluate bursts in the recorded spike trains. Bursts were assigned a quantitative statistical measure of burst 'strength' (or improbability) - the surprise value. Before the lesion, 34% of units in the globus pallidus and 60% of units in the entopeduncular nucleus exhibited bursts. Burst units had a significantly slower discharge rate and a significantly greater variability of discharge than non-burst units. The mean length of the interspike intervals immediately preceding the bursts was significantly longer than the overall median intervals in burst units. After the lesion, 21% of units in the globus pallidus and 11% of the units in the entopeduncular nucleus exhibited bursts. Burst units had significantly higher discharge rates and lower discharge variability after the lesion. In contrast, the lesion had no significant effect on the rate or variability of non-burst units. The differences between bursting and non-bursting units in discharge rate and variability disappeared after the lesion. In globus pallidus, the lesion resulted in a significant reduction in the mean number of bursts per unit, surprise value per burst, mean length of bursts, and number of spikes per burst, and a significant increase in the mean discharge rate of burst units. In entopeduncular nucleus, the small number of bursts recorded after the lesion precluded a useful statistical comparison of the effect of striatal lesions on the properties of the bursts. This study demonstrates that removing striatal projections to globus pallidus and entopeduncular nucleus decreases bursting in these nuclei, indicating that intact striatal projections are necessary for the normal production of bursts in these regions.

Animals↗

Reverse microdialysis of ionotropic glutamate receptor agonists in the rat globus pallidus increased extracellular dopamine.

The globus pallidus (GP) receives a prominent dopamine (DA) input by collaterals from the nigrostriatal pathway. However, the neurochemical regulation of extracellular DA in the GP is unknown at present. In the present study we investigated whether activation of ionotropic glutamate receptors by reverse microdialysis of NMDA and AMPA elicits changes in extracellular DA in the GP. Results show that reverse microdialysis of 70 microM AMPA and of 1 mM NMDA produced a significant and reversible increase of dialysate DA levels to about 130% and 160%, respectively. These data provide evidence that ionotropic glutamate receptors in the GP exert excitatory actions on DA release which might be brought about by actions on presynaptic ionotropic glutamate receptors in the GP or involve stimulation of midbrain DA neurons through trans-synaptic pathways.

Animals↗

Repetitive activation of glutamatergic inputs evokes a long-lasting excitation in rat globus pallidus neurons in vitro.

External globus pallidus (GPe) neurons express abundant metabotropic glutamate receptor 1 (mGluR1) in their somata and dendrites and receive glutamatergic inputs mainly from the subthalamic nucleus. We investigated whether synaptically released glutamate could activate mGluR1s using whole cell and cell-attached recordings in rat brain slice preparations. Repetitive internal capsule stimulation evoked EPSPs followed by a slow depolarizing response (sDEPO) lasting 10-20 s. Bath application of both GABA(A) and GABA(B) receptor antagonists increased the amplitude of sDEPOs. A mixture of AMPA/kainate and N-methyl-d-aspartate receptor antagonists did not alter sDEPOs. The induction of sDEPOs was only partially mediated by mGluR1 because mGluR1 antagonists reduced but failed to completely block the responses. Voltage-clamp recordings revealed that slow inward currents sensitive to mGluR1 antagonist were larger at -60 than at -100 mV, whereas the currents insensitive to mGluR1 antagonist were larger at -100 than at -60 mV. In cell-attached recordings, repetitive internal capsule stimulation evoked long-lasting excitations in GPe neurons, which were also partially suppressed by mGluR1 antagonists. Application of a glutamate uptake inhibitor or an mGluR1 agonist significantly increased the spontaneous firing rate but decreased the excitations to repetitive stimulation. These results suggest that synaptically released glutamate can activate mGluR1, contributing to the induction of long-lasting excitation in GPe neurons and that background mGluR1 activation suppresses the slow mGluR1 responses. Thus mGluR1 may play important roles in the control of GPe neuronal activity.

Animals↗

A Golgi study on the globus pallidus of the mouse.

The globus pallidus (GP) of the mouse was studied by the rapid Golgi silver impregnation method. The GP was composed of large and medium-sized neurons. The large neurons had stellate cell bodies with a mean diameter of 25 micron by 28 micron and five to seven primary dendrites. The somata of the medium-sized neurons were spindle or fusiform in shape, measured 19 micron by 27 micron in average and emitted three to five primary dendrites. The large neurons were located mainly in the central part of the GP, whereas the medium-sized neurons were observed in the peripheral part of the GP. Some GP neurons extended their dendrites into the caudatoputamen complex, sublenticular region or internal capsule. The axons of the GP neurons were seen most frequently to course medially or mediocaudally and to enter the internal capsule or fiber bundles traversing the GP; they were rarely observed to run laterally and to travel into the caudatoputamen complex. Some axons of the GP neurons were also observed to emit intra- or extra-nuclear collaterals extending into the sublenticular region. Four groups of afferent fibers to the GP were observed; (1) fibers descending within the internal capsule or caudatoputamen complex to terminate or to give axon-collaterals to the GP; (2) fibers ascending within the internal capsule or fiber bundles traversing the GP to enter the GP from its medial aspects; (3) fibers traversing the internal capsule laterally to terminate in the GP; and (4) fibers running dorsally through the sublenticular region to terminate in the GP. In addition to these four groups of afferent fibers, terminal branches were seen to arise numerously from many fibers running through the GP.

Afferent Pathways↗

Neural projections from nucleus accumbens to globus pallidus, substantia innominata, and lateral preoptic-lateral hypothalamic area: an anatomical and electrophysiological investigation in the rat.

The anatomical organization and electrophysiological characteristics of a projection from the nucleus accumbens to anteroventral parts of the globus pallidus and to a subpallidal region that includes the substantia innominata (SI), the lateral preoptic area (LPO), and anterior parts of the lateral hypothalamic area (LHA) were investigated in the rat. Autoradiographic experiments, with injections of 3H-proline into different sites in the nucleus accumbens and adjacent caudoputamen, indicate that the descending fibers are organized topographically along both mediolateral and dorsoventral gradients, although labeled fibers from adjacent regions of the nucleus accumbens overlap considerably in the ventral globus pallidus and subpallidal region. Injections confined to the caudoputaman only labeled fibers in the globus pallidus. Retrograde transport experiments with the marker true blue confirmed that only the nucleus accumbens projects to the subpallidal region and that the caudoputamen projects upon the glubus pallidus in a topographically organized manner. In electrophysiological recording experiments single pulse stimulation (0.1 to 0.7 mA; 0.15 msec duration) of the nucleus accumbens changed the discharge rate of single neurons in the ventral globus pallidus and in the SI, LPO, and LHA. Typically, the responses were inhibition of neuronal discharge with latencies of 6 to 18 msec. Single pulse stimulation of the dorsolateral caudoputamen altered the discharge rate of single neurons in dorsal regions of the globus pallidus, with inhibition being the most frequently observed response. The results of these anatomical and electrophysiological experiments are complementary and indicate that fibers from the nucleus accumbens innervate the anteroventral region of the globus pallidus as well as the subpallidal region, while most fibers of the caudoputamen innervate the globus pallidus but not the subpallidal region. It appears, therefore, that these two components of the striatum have different output connections. The possible functional significance of these findings is discussed in relation to the projections of the subpallidal region, which may include an output to the mesencephalic locomotor region, and in relation to the nucleus accumbens afferents from the amygdala and hippocampal formation.

Animals↗

Naloxone antagonizes striatally-induced suppression of globus pallidus unit activity.

This study was designed to examine the ability of naloxone to antagonize the inhibition of neurons in the globus pallidus produced by electrical stimulation of the caudate nucleus. In rats anesthetized with chloral hydrate, bipolar stimulating electrodes were placed in the head of the caudate and seven-barrel micropipettes were utilized for recording extracellular activity of globus pallidus cells as well as for microiontophoretic application of experimental drugs. In most globus pallidus cells which were inhibited by caudate stimulation, application of naloxone (at currents which antagonized morphine-elicited depression) attenuated the caudate-induced effect. Naloxone did not antagonize depression of globus pallidus neurons induced by gamma-aminobutyrate. The results indicate that caudate stimulation causes the release of endogenous enkephalins which act to suppress neuronal activity in the globus pallidus. Thus, this study supports biochemical and histochemical studies which provide evidence for an enkephalinergic component in the striatopallidal projection.

Animals↗

Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis.

BACKGROUND & AIMS: Hyperintense globus pallidus on T1-weighted magnetic resonance images (MRIs) in cirrhotic patients are reported to reflect severity of liver disease; however, their consequence for hepatic encephalopathy is unknown. The aim of this study was to outline a pattern of neuropsychiatric abnormalities in chronic liver failure and its correlation with MRI findings. METHODS: Fifty-one consecutive patients were enrolled in the study. Neuropsychiatric assessment used a standardized protocol, including dichotomized neurological parameters, brief psychiatric rating and psychometric tests, as well as electroencephalography. The severity of liver failure was graded using standard laboratory parameters and the Child-Pugh's classification. Signal intensity of the globus pallidus was determined on sagittal T1-weighted MRIs. RESULTS: Two aspects of neurological dysfunction could be distinguished by principal components analysis: impairment of complex cerebral function and subcortical motor performance. Both neurological categories correlated with severity of liver failure, grade of electroencephalographic abnormalities, and psychometric test results. Additionally, prior bouts of overt encephalopathy indicate progressive dementia. T1-weighted globus pallidus signal intensity did not correlate with any clinical or laboratory test result. CONCLUSIONS: This study shows a characteristic pattern of neurological findings in patients with liver failure and hyperintense globus pallidus on T1-weighted MRIs. Although neurological dysfunction parallels hepatic failure, MRI abnormalities of basal ganglia do not indicate severity of actual hepatic encephalopathy.

Adolescent↗

Comparison of transmitter amino acid levels in rat globus pallidus and neostriatum during hypoglycemia or after treatment with methionine sulfoximine or gamma-vinyl gamma-aminobutyric acid.

The levels of amino acids in globus pallidus, a structure heavily innervated with gamma-aminobutyric acid (GABA)-ergic terminals but few glutamergic terminals, were compared with the levels in neostriatum, a structure richly innervated with glutamergic terminals but intermediate in GABAergic terminals. The level of glutamate in neostriatum was twice as high as in globus pallidus whereas the level of GABA in globus pallidus was three times higher than in neostriatum. The level of aspartate was similar in both regions whereas the level of glutamine was correlated with the level of glutamate. Methionine sulfoximine, a glutamine synthetase inhibitor, reduced the level of glutamine to 10-20% of control in both structures. This reduction was accompanied by the largest decrease in the level of glutamate in neostriatum, indicating that transmitter glutamate turns over more rapidly than other glutamate pools. Likewise, insulin decreased the levels of glutamate and glutamine more in neostriatum than in globus pallidus. gamma-Vinyl GABA increased the level of GABA in globus pallidus more than in neostriatum although the percent increase was largest in neostriatum. Treatment with gamma-vinyl GABA was accompanied by a large reduction in the level of GABA, indicating that a substantial proportion of the glutamine pool is linked to GABA metabolism.

Amino Acids↗

Subthalamic nucleus and internal globus pallidus scale with the rate of change of force production in humans.

The basal ganglia, motor cortex, and cerebellum have been implicated as a circuit that codes for movement velocity. Since movement velocity covaries with the magnitude of force exerted and previous studies have shown that similar regions scale in activation for velocity and force, the scaling of neuronal activity with movement velocity could be due to the force exerted. The present study implemented a parametric functional magnetic resonance imaging (fMRI) design to determine which brain regions directly scale with the rate of change of force production, independent of the magnitude of force exerted. Nine healthy adults produced force with their right middle finger and thumb at 25% of their maximal voluntary contraction across four conditions: (1) fast pulse, (2) fast hold, (3) medium hold, and (4) slow hold. There were three primary findings: (i) the activation volume in multiple regions increased with the duration of the force contraction, (ii) only the activation volume in the bilateral internal globus pallidus and left subthalamic nucleus parametrically scaled with the rate of change of force production, and (iii) there was an inverse relation between the activation volume in the subthalamic nucleus and internal globus pallidus with the rate of change of force production. The current findings are the first to have used neuroimaging techniques in humans to segregate the functional anatomy of the internal globus pallidus from external globus pallidus, distinguish functional activation in the globus pallidus from the putamen, and demonstrate task-dependent scaling in the subthalamic nucleus and internal globus pallidus. We conclude that fast, ballistic force production is preprogrammed, requiring a small metabolic demand from the basal ganglia. In contrast, movements that require the internal regulation of the rate of change of force are associated with increased metabolic demand from the subthalamic nucleus and internal segment of the globus pallidus.

Adult↗

Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease.

BACKGROUND: Increased neuronal activity in the subthalamic nucleus and the pars interna of the globus pallidus is thought to account for motor dysfunction in patients with Parkinson's disease. Although creating lesions in these structures improves motor function in monkeys with induced parkinsonism and patients with Parkinson's disease, such lesions are associated with neurologic deficits, particularly when they are created bilaterally. Deep-brain stimulation simulates the effects of a lesion without destroying brain tissue. METHODS: We performed a prospective, double-blind, crossover study in patients with advanced Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus or pars interna of the globus pallidus and who then underwent bilateral high-frequency deep-brain stimulation. We compared scores on the motor portion of the Unified Parkinson's Disease Rating Scale when the stimulation was randomly assigned to be turned on or off. We performed unblinded evaluations of motor function preoperatively and one, three, and six months postoperatively. RESULTS: Electrodes were implanted bilaterally in 96 patients in the subthalamic-nucleus group and 38 patients in the globus-pallidus group. Three months after the procedures were performed, double-blind, crossover evaluations demonstrated that stimulation of the subthalamic nucleus was associated with a median improvement in the motor score (as compared with no stimulation) of 49 percent, and stimulation of the pars interna of the globus pallidus with a median improvement of 37 percent (P<0.001 for both comparisons). Between the preoperative and six-month visits, the percentage of time during the day that patients had good mobility without involuntary movements increased from 27 percent to 74 percent (P<0.001) with subthalamic stimulation and from 28 percent to 64 percent (P<0.001) with pallidal stimulation. Adverse events included intracranial hemorrhage in seven patients and infection necessitating removal of the leads in two. CONCLUSIONS: Bilateral stimulation of the subthalamic nucleus or pars interna of the globus pallidus is associated with significant improvement in motor function in patients with Parkinson's disease whose condition cannot be further improved with medical therapy.

Activities of Daily Living↗

Immunohistochemical visualization of afferent nerve terminals in human globus pallidus and its alteration in neostriatal neurodegenerative disorders.

The afferent nerve terminal in the human globus pallidus, which receives the projection nerve fibers from both the striatum and the subthalamic nucleus, were clearly visualized immunohistochemically using antibodies to calcineurin, synaptophysin, Met-enkephalin (MEnk) and substance P (SP). In normal control case, MEnk and SP-like immunoreactivities were densely localized in the external and internal pallidal segments, respectively, whereas calcineurin and synaptophysin were distributed throughout the globus pallidus. Calcineurin, synaptophysin, MEnk and SP-like immunoreactive peroxidase products decorated most of the long radiating dendrites and the cell bodies of the pallidal neurons. In the cases with Huntington's disease (HD) and striatonigral degeneration (SND), marked loss of calcineurin, MEnk and SP-like immunoreactivities was seen in the globus pallidus corresponding to areas of striatal neurodegeneration, whereas synaptophysin immunoreactivity remained in areas which revealed almost complete loss of calcineurin, MEnk and SP-like immunoreactivities. Calcineurin, MEnk and SP, which show difference in their localization patterns, may provide reliable markers for the striatal efferent nerve terminals, and synaptophysin for the entire pallidal afferent nerve terminals. This report demonstrates the distribution patterns of these neurochemical molecules in the globus pallidus with HD and SND.

Afferent Pathways↗

Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat.

Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms.

Amygdala↗

Striatal axons to the globus pallidus, entopeduncular nucleus and substantia nigra come mainly from separate cell populations in cat.

The extent to which individual striatal neurons send collaterals to the globus pallidus, entopeduncular nucleus and substantia nigra in the cat brain was determined by double-retrograde tracing with rhodamine fluorescent latex microspheres in combination with either horseradish peroxidase or the fluorescent nuclear dye Diamidino Yellow. In each case, two of the three target nuclei were injected, each with a different tracer, until all three possible combinations of two had been obtained several times. In all cases in which the tracer encroaches upon a striatal target, there are cells labeled in the striatum of a size and shape that is consistent with the observation that they mainly belong to the category of medium striatal cells. Since the striatal projections to the globus pallidus, entopeduncular nucleus and substantia nigra are each topographically organized, the zones of cell-labeling within the striatum vary depending upon the portion of the target nucleus involved by the deposit. Thus, in many cases the fields of striatal cells containing one label overlap only slightly with those in which cells containing the other label occur. In other cases, however, there is extensive overlap of the striatal zones containing cells marked with either tracer. In all cases, very few double-labeled cells can be found, even where hundreds of cells labeled with either tracer are freshly intermingled. Doubly labeled cells occur somewhat more frequently in those cases where the tracers are placed in the entopeduncular nucleus and substantia nigra than in those with the other two combinations, suggesting that striatal axons branch more often to the entopeduncular nucleus and substantia nigra than to the globus pallidus and nigra or globus pallidus and entopeduncular nucleus. These findings confirm, that, in the cat as in the primate, the striatal axons to the substantia nigra arise from cells that are largely separate from the striatopallidal population, and further show that the axons to the globus pallidus and entopeduncular nucleus also emanate mainly from different cells.

Amidines↗

Effects of excitotoxic striatal lesions on single unit activity in globus pallidus and entopeduncular nucleus of the cat.

Striatal projections to the globus pallidus and entopeduncular nucleus are thought to be GABAergic and inhibitory. Thus, striatal lesions might be expected to increase the spontaneous discharge rate of neurons in these nuclei. To test this prediction, we recorded spontaneous single unit activity from awake cats sitting quietly before and 7-160 days after striatal lesions. Striatal lesions were produced by injecting ibotenic acid into the caudate nucleus and putamen. Median, standard deviation, mean, and coefficient of variation of the interspike intervals were calculated for each unit. In globus pallidus the striatal lesion resulted in a significant decrease in median interval length, i.e. an increase in the discharge rate. The prelesion median of 36 ms (S.E.M. = 2.3) decreased 11% to a postlesion value of 32 ms (S.E.M. = 2.1). The lesion also resulted in a significant decrease in the variability of interspike intervals. The coefficient of variation, 1.31 (S.E.M. = 0.08) before the lesion, decreased 25% to 0.97 (S.E.M. = 0.06) after the lesion. In entopeduncular nucleus, the lesion had no statistically significant effect on the rate of activity, but a significant decrease in the variability of activity occurred. The median interval was 33 ms (S.E.M. = 3.3) before the lesion and decreased 2% to 32 ms (S.E.M. = 2.4). The coefficient of variation decreased 48% from 1.44 (S.E.M. = 0.1) to 0.73 (S.E.M. = 0.03). These observations support the hypothesis that loss of GABAergic inputs to the globus pallidus results in disinhibition. The discharge rate in entopeduncular nucleus was not affected by the striatal lesion, suggesting that striatal substance P or subthalamic excitatory inputs may have a role in regulating discharge rate in the entopeduncular nucleus.

Action Potentials↗

Separate neuronal populations of the rat globus pallidus projecting to the subthalamic nucleus, auditory cortex and pedunculopontine tegmental area.

The topographic arrangement of globus pallidus neurons sending axons to the subthalamic nucleus, auditory cortex and pedunculopontine tegmental nucleus was studied in the rat using retrograde fluorescent tracers. Neurons projecting to the subthalamic nucleus were localized in the rostral part of the globus pallidus, while neurons projecting to the auditory cortex and to the pedunculopontine tegmental nucleus were located in the caudal part. The two populations of pallidocortical and pallidotegmental neurons were also distributed in a separate manner within the caudal globus pallidus. The former neurons were large and located more ventromedially, whereas the latter were medium-sized and located more dorsolaterally. Using a retrograde fluorescent tracing technique combined with choline acetyltransferase immunofluorescence histochemistry, it was found that a vast majority of pallidocortical neurons expressed choline acetyltransferase immunoreactivity, and that pallidotegmental neurons rarely exhibited choline acetyltransferase immunoreactivity. A method of retrograde tracing with wheatgerm agglutinin conjugated with horseradish peroxidase associated to immunohistochemistry for glutamate decarboxylase confirmed the GABAergic nature of the pallidotegmental pathway. The present study revealed the independent nature of the globus pallidus neurons projecting to the subthalamic nucleus, auditory cortex and pedunculopontine tegmental nucleus. Within this cellular arrangement, the presence of functionally distinct neuronal populations at the caudal pallidal level was also identified, with large cholinergic cells innervating the neocortex and medium-sized GABAergic cells "feeding" the mesencephalic tegmentum.

Animals↗