Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high affinity choline uptake decrease after lesion of the nucleus basalis

Monosialoganglioside GM₁ and nerve growth factor (NGF) were administered alone or concomitantly to adult male rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM). High-affinity choline uptake (HACU) rate and choline acetyltransferase (ChAT) activity were measured, 4 and 21 days after surgery, respectively, in the frontal and parietal cortices of both hemispheres. A 33–34% decrease in HACU rate and a 43-39% decrease in ChAT activity was found in the ipsilateral cortices 4 and 21 days, respectively, after the lesion. If the lesioned rats received NGF (10 μg i.c.v.) twice a week or daily administrations of GM₁ (30 mg/kg, i.p.), beginning immediately after surgery the decrease in HACU rate and ChAT activity was smaller. If NGF and GM, were given concomitantly no decrease in HACU rate and ChAT activity was detected in the lesioned hemisphere and a slight increase occurred in the contralateral hemisphere. However, after the concurrent administration of NGF (10 μg i.c.v.) and the inactive dose of GM₁ 10 mg/kg i.p. no decrease in HACU and ChAT activity was also found in the lesioned rats. The latter finding indicates a potentiation by GM₁ of NGF effects on the cholinergic neurons of the IBM. The two drugs may either antagonize the neurotoxic effects of ibotenic acid or stimulate a compensatory activity in the remaining neurons.     

Behaviorally specific limb use deficits following globus pallidus lesions in rats

The effects of bilateral globus pallidus lesions were observed in rats trained to perform a somatosensory/proprioceptive guided forelimb reaching task. Postlesion reaching became very inaccurate, characterized by gross abnormalities in limb and body posture. Postural abnormalities and paw use deficits were not observed in other situations. These results suggest that pallidal damage does not result in a simple motor deficit but interferes with motor performance when movements depend upon somesthetic and proprioceptive feedback.     

Projections of the feline globus pallidus

The organization of globus pallidus (GP) projections was studied in cats using autoradiographic and horseradish peroxidase (HRP) techniques. Both methods confirmed the existence of a topographically organized projection to subthalamic nucleus (STN). Although all but the most caudal GP projects to STN, the heaviest projection is to the lateral two-thirds. In addition, HRP studies showed that the GP projection to the medial part of substantia nigra, pars reticulata receives projections from the rostral lateral GP, while lateral substantia nigra receives input from caudal GP. There is in addition a small projection from caudal GP to the caudal lateral mesencephalon. This most caudal projection of GP arises from the portion of GP which projects the least to the subthalamic nucleus. Mesencephalic and pontine cells labeled after injection of horseradish peroxidase into STN were in areas receiving projections from GP and entopeduncular nucleus, suggesting there may be reciprocal relationships between these areas. Labeled cells were located in the lateral part of subthalamic nucleus after injection into the lateral portion of substantia nigra pars reticulata, but cells were not labeled after medial injection. Pontine injections of HRP also revealed that cells in fields of Forel and zona incerta project to pons but very few subthalamic nucleus cells project there.     

Deoxyglucose uptake and choline acetyltransferase activity in cerebral cortex following lesions of the nucleus basalis magnocellularis

The uptake of [3H]2-deoxyglucose (2-DG) into various brain regions of rats with unilateral or bilateral lesions of the nucleus basalis magnocellularis (nBM) was measured. The activity of choline acetyltransferase (ChAT) in these brain regions was also determined. Lesions of the nBM caused a significant decrease in cortical ChAT activity but had no effect on 2-DG accumulation. Pentobarbital treatment reduced 2-DG accumulation in all brain areas examined and these reductions were not influenced by the nBM lesions. The results indicate that a decrease in the cholinergic innervation of the cortex does not influence cortical glucose utilization. It appears unlikely, therefore, that the reported decrease in cortical glucose utilization in Alzheimer's disease is related to degeneration of the nBM-cortical cholinergic projection.     

Modifications in the cortical regional distribution of choline acetyltransferase, somatostatin and somatostatin binding sites in the normal rat and following lesion of the nucleus basalis

The regional distribution of choline acetyltransferase activity, somatostatin levels and 125I-CGP 23996 (a somatostatin agonist analog) specific binding sites in 10 separate zones of the cerebral cortex was analyzed. The study was performed in normal rats as well as 15 days after unilateral excitotoxic lesion of the nucleus basalis. A significant correlation was found in the controls between the regional distribution of choline acetyltransferase activity and somatostatin concentrations, both most highly concentrated in the piriform and entorhinal cortex. In contrast, the regional density of 125I-CGP 23996 binding sites correlated neither with choline acetyltransferase activity nor with somatostatin levels. Unilateral lesions of the basal forebrain decreased choline acetyltransferase activity in the frontal and parietal cortex, while 125I-CGP 23996 binding decreased in frontal and occipital regions. No decrease in somatostatin content was observed. The results suggest that, in rats, cortical somatostatin receptors could be associated with cholinergic afferents from the nucleus basalis in the frontal cortex only.     

苍白球在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨苍白球在电针镇痛及兴奋尾壳核镇痛中的作用。结果表明 :电针可以延长辐射热引起的缩腿潜伏期 ,电针或兴奋尾壳核可抑制丘脑束旁核神经元的伤害性反应 ;苍白球微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响 ,与毁损前相比有显著性差异 (P <0 .0 5 ) ,与苍白球微量注射生理盐水 7d后 ,电针可延长大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比有显著性差异 (P <0 .0 5 )。结果提示 :苍白球在电针及兴奋尾壳核镇痛中发挥重要作用     

Three-dimensional representation and cortical projection topography of the nucleus basalis (Ch4) in the macaque: concurrent demonstration of choline acetyltransferase and retrograde transport with a stabilized tetramethylbenzidine method for horseradish peroxidase

Ninety-six percent of the nucleus basalis neurons that project to the neocortex contain choline acetyltransferase. These projections from the cholinergic component of the nucleus basalis (Ch4) are topographically organized so that each cortical area receives most of its cholinergic input from a different Ch4 sector. The three-dimensional reconstruction of these sectors reveals the presence of a complex structure. A stabilization procedure that was used in these experiments maintains all the advantages of the tetramethylbenzidine method for horseradish peroxidase while eliminating the vulnerability of the reaction-product to high pH and dehydrating agents.     

Regional heterogeneity of choline acetyltransferase activity in primate neocortex

Choline acetyltransferase activity in precentral and temporal regions of primate neocortex is 2.5-fold higher than in occipital cortex. These results suggest large differences in the density of innervation in different regions of primate neocortex by the nucleus basalis of Meynert.     

Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high affinity choline uptake decrease after lesion of the nucleus basalis

Monosialoganglioside GM₁ and nerve growth factor (NGF) were administered alone or concomitantly to adult male rats with a unilateral ibotenic acid lesion of the nucleus basalis magnocellularis (NBM). High-affinity choline uptake (HACU) rate and choline acetyltransferase (ChAT) activity were measured, 4 and 21 days after surgery, respectively, in the frontal and parietal cortices of both hemispheres. A 33–34% decrease in HACU rate and a 43-39% decrease in ChAT activity was found in the ipsilateral cortices 4 and 21 days, respectively, after the lesion. If the lesioned rats received NGF (10 μg i.c.v.) twice a week or daily administrations of GM₁ (30 mg/kg, i.p.), beginning immediately after surgery the decrease in HACU rate and ChAT activity was smaller. If NGF and GM, were given concomitantly no decrease in HACU rate and ChAT activity was detected in the lesioned hemisphere and a slight increase occurred in the contralateral hemisphere. However, after the concurrent administration of NGF (10 μg i.c.v.) and the inactive dose of GM₁ 10 mg/kg i.p. no decrease in HACU and ChAT activity was also found in the lesioned rats. The latter finding indicates a potentiation by GM₁ of NGF effects on the cholinergic neurons of the IBM. The two drugs may either antagonize the neurotoxic effects of ibotenic acid or stimulate a compensatory activity in the remaining neurons.     

Role of postural deficits in oro-ingestive problems caused by globus pallidus lesions

There is a large literature demonstrating that rats with globus pallidus lesions have ingestional problems. In an effort to understand the bases of these deficits, the ingestional activity of normal and brain-damaged animals was subjected to scrutiny. Rats were trained to lick a spout recessed behind a Plexiglas wall for 8% sucrose solution. The characteristic interlick interval and lick duration distributions observed in normal animals were severely disrupted by globus pallidus lesions. This disturbance was, in large part, due to an inability to correctly position the mouth with respect to the spout and maintain that position for a burst of licks, activities which normally ensure consistently efficient ingestion. After pallidal lesions, animals often miss the spout altogether. When they do find the spout, only the first few licks are on target. The head then drifts away from the correct position and subsequent licks miss the spout. Animals' ability to continue licking during slow lateral displacement of the spout was also tested. Animals with pallidal lesions showed severe deficits. In addition to problems with head positioning, pallidal animals failed to adapt their body posture to enable licking at different spout locations. In relation to clinical and experimental findings, these data implicate the basal ganglia in feedback-regulated control of axial and proximal muscles.     

Alteration of neuronal responses in the subthalamic nucleus following globus pallidus and neostriatal lesions in rats

Kainic acid (2-4 days) or ibotenic acid (7-9 days) lesions of the globus pallidus or neostriatum altered the responsiveness of subthalamic nucleus neurons to electrical stimulation of the agranular frontal cortex. Three changes in responsiveness were seen following pallidal lesion: a) An increase in the proportion of responding cells as compared to controls (approximately 90% vs. 60%); b) an increase in the total duration of the evoked response (62.5 ms vs. 28.6 ms); 3) an increase in magnitude of response (9.76 spikes per stimulus vs. 3.24). Both an increase in firing rate (17.94 spikes/s vs. 8.23) and a change to a bursty spontaneous firing pattern were seen. Lesion of the neostriatum had fewer but opposite effects including decreased firing rate (7.21 spikes/s) and decreased total response duration (18.9 ms). These results suggest that the normal tonic inhibition of the subthalamic nucleus by the globus pallidus may play an important role in controlling subthalamic neuronal spontaneous activity and responsiveness. The neostriatum may influence the subthalamic nucleus via the globus pallidus. Globus pallidus lesions may have important consequences on the specificity of cortical control of the subthalamic nucleus and may alter subthalamic influence on basal ganglia output.     

Labeled norepinephrine uptake and release in rat globus pallidus

The uptake and release of [3H]norepinephrine [( 3H]NE) were investigated using isolated rat globus pallidus slices to determine the possible neurotransmitter role of this catecholamine. The uptake into these slices was linear for the first 10 min. Kinetic analysis indicated two components of NE accumulation, one representing a high (Km1 2.9 X 10(-7) M and Vmax1 1.4 pmol/mg/10 min) and other a low (Km2 1.6 X 10(-6) M and Vmax2 5 pmol/mg/10 min) affinity uptake system. Desmethylimipramine at a concentration of 10(-5) M reduced the high affinity uptake of [3H]NE by 25% of the control values. Electrical stimulation of the slices increased the efflux of [3H]NE and its metabolites from tissues preloaded with [3H]NE, in a current- and frequency-dependent fashion. The release of [3H]NE and its metabolites induced by electrical stimulation (1 mA, 20 Hz, 1 ms for 2 min) was inhibited by tetrodotoxin (10(-6) M), and by a calcium-free medium containing EGTA (10(-4) M) or medium with a high magnesium-concentration (2 X 10(-2) M). These findings provide strong evidence for the neurotransmitter role of NE, in these tissues.     

The influence of the subthalamic nucleus upon the damage to the dopamine system following lesions of globus pallidus in rats

Lesioning or stimulating the subthalamic nucleus (STN) in patients with Parkinson's disease, or in animal models of parkinsonism, alleviates many of the symptoms and so it is tempting to think of the STN as a part of the cause of Parkinson's disease. The globus pallidus (GP) is thought to have a tonic inhibitory action on the STN. An ibotenic acid injection into the GP in rats removes the cells of the GP and, over the following 6 weeks, a progressive loss of dopamine cells (counted stereologically in sections stained for tyrosine hydroxylase) develops in substantia nigra (SN). In this investigation we show that, when animals have the STN cells destroyed by very small ibotenic acid injections, their dopamine neurons are not damaged. Furthermore, if a lesion to the GP follows a lesion of STN then the dopamine cells also survive this double insult, at least for the first 3 weeks following the lesion. The experiments provide good reason to suspect that, at least in the short term, increased activity in the STN is a contributory cause of the loss of dopamine cells which follows the lesion of the GP in rats. Whether or not this is part of the mechanism of cell loss in Parkinson's disease, the rats with GP lesions at least provide an opportunity to test strategies that might protect dopamine cells from slowly developing damage. Removing the STN seems to be neuroprotective in this new model of dopamine degeneration.     

Effect of surgical deafferentation of the supraoptic nucleus on its choline acetyltransferase content

The concentration of choline acetyltransferase, a specific marker for cholinergic neurons, was determined in the supraoptic nucleus after a variety of lesions. Surgical lesions immediately rostral as well as medial and lateral to the nucleus did not affect the concentration of the enzyme. Only lesions which separated the nucleus from the posterior part of the lateral hypothalamus slightly decreased its concentration in choline acetyltransferase. It is concluded that the bulk of the cholinergic neurons is in the supraoptic nucleus or its immediate vicinity.     

Subthalamic projections to the globus pallidus: An electrophysiological study in the rat

The connections between the subthalamic nucleus (STN) and the globus pallidus (GP) were investigated electrophysiologically. By the use of stimulating electrode arrays it was determined that the predominant response of globus pallidus neurons to stimulation of the subthalamic nucleus was inhibition. A smaller proportion of short-latency orthodromic activation was also observed. Antidromic activation from the subthalamic nucleus was seen occasionally, although more laterally located in the pallidum. The results demonstrate the existence of reciprocal connections between these two regions and show that the predominant effect of subthalamic activation is inhibition of pallidal cells.     

Amphetamine-induced Fos expression is evident in gamma-aminobutyric acid neurons in the globus pallidus and entopeduncular nucleus in rats treated with intrastriatal c-fos antisense oligodeoxynucleotides

Double immunostaining for Fos and gamma-aminobutyric acid (GABA) was used in a previously established animal model of striatal dysfunction to examine whether GABA-immunoreactive neurons in the globus pallidus (GP) and entopeduncular nucleus (EP) are activated to express Fos immunoreactivity by intraperitoneal injection of amphetamine. Striatal efferent activity was suppressed by intrastriatal infusions of antisense oligodeoxynucleotide targeted to the messenger RNA of the immediate early gene, c-fos. This suppression produced robust rotational behavior and expression of Fos in the ipsilateral GP and EP following amphetamine challenge. The expression of Fos in the ipsilateral GP and EP following amphetamine challenge is not observed in na?ve or control antisense-treated animals. Quantitative analysis revealed that a majority of the amphetamine-activated (Fos-immunoreactive) neurons in the GP and EP express GABA. The present results suggest that inhibitory GABAergic projection neurons within these two nuclei are regulated by inhibitory striatal output and suggests that decreased inhibitory striatal output may contribute to the motor dysfunction observed in patients with Huntington's disease.