Integration and segregation of limbic cortico-striatal loops at the thalamic level: an experimental tracing study in rats

The frontal lobe and the basal ganglia are involved in a number of parallel, functionally segregated circuits. Information is thought to pass from distinct parts of the (pre)frontal cortex, via the striatum, the pallidum/substantia nigra and the thalamus, back to the premotor/prefrontal cortices. Currently, different views exist as to whether these circuits are to be considered as open or closed loops, as well as to the degree of interconnection between different circuits. The main goal of the present study is to answer some of these questions for the limbic corticostriatal circuits. The latter circuits involve the nucleus accumbens, the ventral pallidum/dorsomedial substantia nigra pars reticulata, the medial parts of the mediodorsal and ventromedial thalamic nuclei and the prefrontal cortex. Within the nucleus accumbens, a core and a shell region are recognized on the basis of anatomical and functional criteria. The shell of the nucleus accumbens projects predominantly to the mediodorsal, the midline and the reticular thalamic nuclei via the ventral pallidum, whereas the core reaches primarily the medial part of the ventromedial thalamic nucleus, the intralaminar and mediodorsal thalamic nuclei via a relay in the dorsomedial substantia nigra pars reticulata. By means of double labeling experiments with injections of anterograde tracers in both the ventral pallidum and the substantia nigra of rats, we were able to demonstrate that circuits involving the shell and the core of the nucleus accumbens remain largely segregated at the level of the thalamus. Only restricted areas of overlap of ventral pallidal and reticular nigral projections occur in the mediodorsal and ventromedial thalamic nuclei, which allows for a limited degree of integration, at the thalamic level, of information passing through the two circuits.     

Aspartate, glutamate and GABA levels in pallidum, substantia nigra, center median and dorsal raphe nuclei after cylindric lesion of caudate nucleus in cat

Aspartate, glutamate and GABA levels were determined in afferent and efferent projection nuclei of the striatum after unilateral cylindric lesion in the head of the caudate nucleus in cats. Two and four weeks after operation, GABA content was significantly reduced in substantia nigra and pallidum ipsilateral to the lesion. Glutamate (GLU) level was decreased in substantia nigra and pallidum only 4 weeks after lesion, whereas aspartate content in substantia nigra decreased significantly already after 2 weeks. No changes in the contents of these amino acids were detected in the dorsal raphe nucleus, which receives a projection from the caudate, as well as in the center median nucleus, which projects to the striatum. These experiments using longer survival times substantiate the role of GABA in caudato-pallidal and caudatonigral projections. The possibility is discussed that aspartate (ASP) could function as transmitter of cortico-nigral fibers.     

3H]SCH 23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions

The distribution of D1 dopamine receptors was studied autoradiographically in the basal ganglia of the cat, monkey and human. These receptor binding sites were labeled directly with the D1-selective antagonist [3H]SCH 23390, and ligand-binding assays were performed concurrently. Serial- or same-action analysis permitted comparisons among D1 binding distributions, acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity. In all species studied, the dorsal striatum exhibited patches of particularly dense D1 binding in correspondence with acetylcholinesterase-poor striosomes. Highly patterned binding was present in the ventral striatum. Distinctions in binding density were observed among the subdivisions of the globus pallidus and of the substantia nigra. The external segment of the pallidum was extremely sparse in D1 binding, whereas the internal segment (or entopeduncular nucleus in the cat) was a site of high D1 binding density. The binding density was greatest in the core of the internal segment, and tyrosine hydroxylase-positive fibers surrounded and weakly dispersed themselves through this core. Weak binding was present in the ventral pallidum. In the substantia nigra, the pars reticulata demonstrated the densest binding, particularly medially. The pars compacta showed much sparser binding, though some of its tyrosine hydroxylase-positive neurons had dendrites extending ventrally into the zone of dense D1 binding in the pars reticulata. We conclude that [3H]SCH 23390-defined D1 binding is compartmentalized in the dorsal striatum and that, particularly in relation to the reported distributions of striatal D2 dopamine receptors, this is likely to be of functional significance in the dopaminergic modulation of intrastriatal neurotransmission as well as of afferent and efferent neurotransmission. The segregated localizations of D1 receptors in the substantia nigra suggest predominant activation of the pars reticulata, including ventral and medial regions adjacent to the densocellular zone. Specific pathways from compartments in the striatum to subdivisions of the pallidum may also be differentially modulated by dopamine acting via distinct receptor subtypes. At the level of the pallidum, such D1 modulation appears to be restricted to the internal segment, which projects to the thalamus, rather than to the external pallidum, which projects to the subthalamic nucleus.     

The distribution of dynorphinergic terminals in striatal target regions in comparison to the distribution of substance P-containing and enkephalinergic terminals in monkeys and humans.

Single- and double-label immunohistochemical techniques using several different highly specific antisera against dynorphin peptides were used to examine the distribution of dynorphinergic terminals in globus pallidus and substantia nigra in rhesus monkeys and humans in comparison to substance P-containing and enkephalinergic terminals in these same regions. Similar results were observed in monkey and human tissue. Dynorphinergic fibers were very abundant in the medial half of the internal pallidal segment, but scarce in the external pallidal segment and the lateral half of the internal pallidal segment. In substantia nigra, dynorphinergic fibers were present in both the pars compacta and reticulata. Labeling of adjacent sections for enkephalin or substance P showed that the dynorphinergic terminals overlapped those for substance P in the medial half of the internal pallidal segment, but showed only slight overlap with enkephalinergic terminals in the external pallidal segment. The substance P-containing fibers were moderately abundant along the borders of the external pallidal segment, and enkephalinergic fibers were moderately abundant in parts of the internal pallidal segment. Dynorphinergic and substance P-containing terminals overlapped extensively in the nigra, and both extensively overlapped enkephalinergic fibers in medial nigra. Immunofluorescence double-labeling studies revealed that dynorphin co-localized extensively with substance P in individual fibers and terminals in the medial half of the internal pallidal segment and in substantia nigra. Thus, as has been found in non-primates, dynorphin within the striatum and its projection systems appears to be extensively localized to substance P-containing striatopallidal and striatonigral projection neurons. Nonetheless, our results also raise the possibility that a population of substance P-containing neurons that projects to the internal pallidal segment and does not contain dynorphin is present in primate striatum. Our results also suggest the possible existence of populations of striatopallidal and striatonigral projection neurons in which substance P and enkephalin or dynorphin and enkephalin, or all three, are co-localized. Thus, striatal projection neurons in primates may not consist of merely two types, one containing substance P and dynorphin and the other enkephalin.     

The ventral striatopallidal complex: an immunocytochemical analysis of medium-sized striatal neurons and striatopallidal fibers in the basal forebrain of the rat

The borders of the ventral striatum and ventral pallidum of the rat brain have been studied with immunocytochemistry for two protein markers that are present in these regions. One of these, DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein, Mr 32,000), is specifically enriched in medium-sized spiny neurons of the neostriatum and in the projection of these neurons upon pallidal regions. The second protein, synaptophysin, a marker for nerve terminals, effectively labels pallidal synapses. In the ventral striatum, neurons strongly immunoreactive for DARPP-32 were densely packed throughout its three components, i.e., the fundus striati and the nucleus accumbens septi, the olfactory tubercle, and the cell bridges that connect the tubercle with the overlying caudatoputamen and the nucleus accumbens. In the ventral pallidum, axons and axon terminals immunoreactive for DARPP-32 and axon terminals immunoreactive for synaptophysin were clearly delineated. As defined by these markers, the ventral pallidum was traced rostroventrally from the globus pallidus to the superficial layers of the olfactory tubercle, medially to the insula Calleja magna and the lateral septum, laterally to the pyriform cortex, and caudally to the anterior amygdaloid area. The ventral striatum and pallidum were densely intermingled in parts of the olfactory tubercle and medial forebrain bundle regions, and clearly separated in more caudal regions. The insulae Callejae did not contain typical striatal or pallidal staining patterns. Our results indicate that the ventral striatopallidal complex in the rat extends both rostrocaudally and dorsoventrally, in a highly complex, intermingled fashion, throughout most of the basal forebrain.     

Efferent fibers of the subthalamic nucleus in the monkey. A comparison of the efferent projections of the subthalamic nucleus,substantia nigra and globus pallidus

A study was made to determine the efferent projections of the subthalamic nucleus in the monkey. Because of the impossibility of producing lesions in this nucleus, not involving adjacent structures, lesions were produced by different stereotaxic approaches. Comparisons were made with degeneration resulting from localized lesions in substantia nigra and globus pallidus. Degeneration resulting from these lesions was studied in transverse and sagittal sections stained by the Nauta-Gygax method. Efferent fibers from the subthalamic nucleus pass through the internal capsule into the medial pallidal segment; a few fibers are distributed to the lateral pallidum. Some subthalamic efferent fibers pass to the contralateral globus pallidus via the dorsal supraoptic decussation, but none projection to the thalamus. Nigral efferent fibers project to parts of the ventral anterior (VAmc) and ventral lateral (VLm) thalamic nuclei. The medial pallidal segment gives fibers to: (1) ventral anterior (VA), ventral lateral (VLo) and centromedian (CM) thalamic nuclei, and (2) the pedunculopontine nucleus. The lateral pallidal segment projects exclusively to the subthalamic nucleus. Thalamic projections of the substania nigra and globus pallidus are distinctive. Subthalamic projections to the globus pallidus are more profuse than those of the substantia nigra. The following hypothesis is presented: Subthalamic dyskinesia, due to lesions in the subthalamic nucleus, is a consequence of removal of inhibitory influences acting upon the medial segment of the globus pallidus.     

The neurological basis of striatally induced head-turning in the rat: The effects of lesions in putative output pathways

Turning of the head towards the contralateral side was induced in the conscious unrestrained rat by electrical stimulation of the neostriatum through permanent indwelling electrodes. The possible output pathways by which this response was mediated were examined using ablative and neurotoxin lesions. Contralateral head-turning was abolished or greatly attenuated by electrolytic lesions of the globus pallidus or substantia nigra on the stimulated side. Lesions of the sensory cortex, superior colliculi, ventromedial thalamic nucleus or dopaminergic nigrostriatal pathway were ineffective.It is concluded that descending projections from the pallidum and/or substantia nigra to the brain stem may be important for the mediation of head-turning induced by striatal stimulation.     

Comparative activities of tetanus and botulinum toxins

Using immunohistochemical methods we have studied the distribution of substance P fibers, terminals and perikarya throughout the basal ganglia of baboons and at selected levels of the human brain. Immunoreactivity in the substantia nigra pars reticulata, internal segment of the globus pallidus and ventral pallidum was dense and of a characteristic, “woolly-fiber” morphology. The caudate nucleus and putamen contained sharply circumscribed patches of dense immunoreactivity superimposed on a moderately stained background. The external division of the globus pallidus displayed very little immunoreactivity. Two morphological types of immunoreactive cell bodies were present in the caudate nucleus, putamen and nucleus accumbens, and were clustered within the dense patches. The distribution of immunoreactive perikarya within the striatum differed from that reported for rats, as immunoreactive neurons were distributed evenly throughout the rostrocaudal extent rather than being concentrated in the rostral portions.     

Topographic distribution of the axonal endings from the sensorimotor and associative striatum in the macaque pallidum and substantia nigra

The striatopallidonigral connection was studied by injecting anterograde tracers into either the associative or the sensorimotor striatum in ten macaques. The results were analyzed using a precise cartographic method. Injections into various parts of the associative striatum (caudate nucleus and ventromedial putamen) produced a labeling of axons in the dorsomedial and ventral pallidal regions. These associative regions occupied two-thirds of the lateral pallidum and one-third of the medial pallidum. Bands of labeled axons from the sensorimotor striatum (dorsolateral putamen) were found in the remaining, central part of the two pallidal nuclei. In the substantia nigra, the rostral associative striatum projected medially to the pars reticulata, while the caudal parts projected laterally. The whole pars reticulata and lateralis thus appeared to receive associative striatal inputs. The sensorimotor striatal territory projected to the central part of the pars reticulata/lateralis. It was concluded that the two functional territories remain separate in the two pallidal nuclei but overlap in the middle third of the substantia nigra. However, due to their great size, the pallidal neurons located at the border of the two territories may receive striatal inputs from both the associative and the sensorimotor components in the same way that nigral neurons do.     

The distribution of enkephalin immunoreactive fibers and terminals in the monkey central nervous system: An immunohistochemical study

Using immunohistochemical techniques, the distribution of met-enkephalin fibers and terminals was studied in the central nervous system of adult old-world monkeys. Areas which showed the greatest density of immunoreactivity included substantia gelatinosa, nucleus tractus solitarius, nucleus parabrachialis, substantia nigra, median eminence, globus pallidus (external segment), patches within the striatum and the region of nucleus accumbens and the olfactory area. Striking and discrete zones of enkephalin immunoreactive fibers and terminals which did not conform to known nuclear boundaries were observed in the latter areas.The distribution of enkephalin in the monkey is compared to what has been described in the rat central nervous system. In general, the two species are similar, however, differences were observed in some areas including the hypoglossal nucleus, substantia nigra and in the region of the nucleus accumbens and olfactory area. The results are discussed with regard to the possible functional significance of enkephalin localization in regions related to regulation of pain, mood, and autonomie function.     

Nigro-amygdaloid fiber connections in the cat

Relatively discrete unilateral lesions were made in the lateral portion of the substantia nigra of eight cats and in the medial substantia nigra of two. After a 10-day survival period the animals were killed, brains were stored in buffered 10% formalin, and frozen sections were stained for degenerating axons and terminals, or by Weil and cresyl violet methods. Electrodes passed through the medial suprasylvian gyrus, pulvinar and/or posterolateral thalamic nucleus and the medial geniculate body. The stria terminalis and hippocampus were undamaged. Degeneration from the lesion followed two paths. One projected through the reticular nucleus into the internal capsule and then ventrolaterally below the putamen to enter the lateral and central amygdaloid nuclei, with degenerated terminals. The second path ran dorsolaterally in the internal capsule to enter the external capsule where some of the fibers spread into the lateral amygdaloid nucleus. It appears that some of the terminals in the lateral amygdaloid nucleus are from the external capsule. Perhaps these connections link the extrapyramidal system to the amygdaloid body.     

Abundance and location of DARPP-32 in striato-tegmental circuits of domestic chicks

The striatum is reciprocally connected to the brainstem dopaminergic nuclei and receives a strong dopaminergic input. In the present study the spatial relation between the dopaminergic and dopaminoceptive structures of the avian medial striatum (formerly: lobus parolfactorius) was observed by confocal laser scanning microscope in the domestic chick (Gallus domesticus). We also analysed the connections in the area ventralis tegmentalis and the substantia nigra. To label the dopaminergic structures, anti-tyrosine hydroxylase was used and DARPP-32 (dopamine and cAMP regulated phosphoprotein) was a marker of dopaminoceptive elements. The tyrosine hydroxylase positive fibres formed baskets of juxtapositions around the DARPP-32 containing cells of the medial striatum. However, such baskets were also observed to juxtapose DARPP-32 immunonegative cells. In the tegmentum, DARPP-32 was observed in axons descending from the telencephalon via the ansa lenticularis. These varicose fibers innervated the ventral tegmental area and substantia nigra and were often juxtaposed to dopaminergic neurons and dendrites. Approximately 40% of the striatal projection neurons targeting the ventral tegmentum, and 60% of striatal projection neurons targeting the nigra were immunoreactive to DARPP-32, as revealed by retrograde pathway tracing with Fast Blue. Endogenous dopamine may exert a retrograde synaptic effect on the afferent striato-tegmental fibers, apart from the reported extrasynaptic action. The abundance of juxtapositions observed in the avian brainstem and medial striatum corroborates the possibility of reciprocal striato-tegmental circuits, relevant to the reinforcement of behaviour.     

Anatomy and physiology of substantia nigra and retrorubral neurons studied by extra- and intracellular recording and by horseradish peroxidase labeling

The question of origin of the excitatory and inhibitory responses that occur in neostriatal neurons following electrical stimulation of the substantia nigra is complicated by the possible spread of stimulus currents to numerous unspecifiable systems of neuronal elements. The present work begins to address this problem through the study of conduction properties of specific nigral and perinigral neurons in the cat. Neurons of pars compacta of substantia nigra and of the retrorubral area were found to have similar latencies for antidromic activation, whether from caudate nucleus stimuli (6.8–8 ms) or medial forebrain bundle stimulation (2.4–6.4 ms).The soma-dendritic features of both pars compacta and retrorubral neurons (revealed by intracellular injection of horseradish peroxidase) resembled the sparsely-branched, medium-sized substantia nigra neurons known from Golgi studies to have long dendrites with scattered and mainly distally-located spine-like appendages. Two types of pars compacta neurons were found; one with an ascending axon lacking collateral branches, and another with a descending axon that issued collaterals which terminated in the compacta, in pars reticulata, and possibly in retrorubral areas. Despite failure to detect as ascending axonal trajectory for this latter neuron, both types of pars compacta cells responded antidromically to stimulation of the caudate nucleus or medial forebrain bundle.The conduction time for impulse propagation in axons of pars compacta or retrorubral neurons suggests that either may mediate at least some of the excitatory responses that are known to occur in neostriatal neurons following stimulation of the substantia nigra in the cat. However, these conduction times are not compatible with the production of other excitatory responses which are commonly observed in the cat striatum at latencies shorter than 6 to 7 ms following stimulation of the substantia nigra.     

Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects

In an attempt to evaluate the cellular organization and efferent projections of the nucleus tegmenti pedunculopontinus pars compacta, several experiments were performed in the rat. From measurements of neurons in the nucleus tegmenti pedunculopontinus pars compacta in Nissl-stained sections, the nucleus was observed to contain many large neurons which made it possible to demarcate this nucleus from surrounding pontomesencephalic reticular formation. Two other neuronal populations, medium and small neurons, were also seen in the nucleus tegmenti pedunculopontinus pars compacta. Detailed measurements showed that 90% by volume of all neurons in the nucleus tegmenti pedunculopontinus pars compacta were large and medium-sized neurons. After injections of [ ³H]leucine into the nucleus tegmenti pedunculopontinus pars compacta, transported label was observed in dorsally and ventrally coursing ascending fibers. The dorsally coursing fibers entered the centrolateral nucleus and centre median-parafascicular complex of the thalamus. The ventrally coursing fibers produced accumulation of silver grains in the ventral tegmental area, substantia nigra pars compacta, subthalamic nucleus, zona incerta and lateral hypothalamus. Crossed fibers of the nucleus tegmenti pedunculopontinus pars compacta were observed sparsely at the levels of the thalamus and posterior commissure, and to a greater degree through the supraoptic commissure of Meynert. Much less anterograde labeling was seen in the equivalent terminal sites on the contralateral side of the brain. By electron microscopic autoradiography major terminal sites of axons of the nucleus tegmenti pedunculopontinus pars compacta were examined in rats injected with [ ³H]leucine in the nucleus tegmenti pedunculopontinus pars compacta and later injected with horseradish peroxidase in the striatum and pallidum. Statistical data showed preferential radiolabeling of terminals forming asymmetrical synaptic contact with dendrites in the centrolateral nucleus, centre median-parafascicular complex and subthalamic nucleus. Apparent terminations in the substantia nigra pars compacta proposed in earlier studies and shown in the present light microscopic autoradiograms were not supported by this ultrastructural analysis. Several radiolabeled terminals of the asymmetrical type contacting horseradish peroxidase labeled dendrites in the thalamus confirmed direct input from the nucleus tegmenti pedunculopontinus pars compacta to the thalamostriate projection neurons. [ ³H]choline injections into the thalamus and subthalamic nucleus produced retrograde perikaryal labeling of large neurons in the nucleus tegmenti pedunculopontinus pars compacta. These neurons were unlabeled after [ ³H]choline injections in the substantia nigra. Other findings suggested retrograde transport of [ ³H]choline through cholinergic terminals as well as cholinergic fibers of passage. These data suggested a selective uptake mechanism for cholinergic fibers of passage.The results emphasize the cholinergic nature of the nucleus tegmenti pedunculopontinus pars compacta innervation of the thalamus and subthalamic nucleus. Large neurons in the nucleus tegmenti pedunculopontinus pars compacta seem responsible for this cholinergic innervation and probably provide the axon terminals making asymmetrical synapses in the thalamus and subthalamic nucleus as described above. In addition, large neurons as well as medium and small ones in the nucleus tegmenti pedunculopontinus pars compacta whose transmitters and exact destinations remain unknown send a number of axons through the supraoptic commissure of Meynert to innervate the contralateral subthalamic nucleus.     

Excitatory amino acid binding sites in the basal ganglia of the rat: a quantitative autoradiographic study.

Quantitative receptor autoradiography was used to determine the distribution of excitatory amino acid binding sites in the basal ganglia of rat brain. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, kainate, quisqualate-sensitive metabotropic and non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had their highest density in striatum, nucleus accumbens, and olfactory tubercle. Kainate binding was higher in the lateral striatum but there was no medial-lateral striatal gradient for other binding sites. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites were most dense in the nucleus accumbens and olfactory tubercle. There was no dorsal-ventral gradient within the striatal complex for the other binding sites. Other regions of the basal ganglia had lower densities of ligand binding. To compare binding site density within non-striatal regions, binding for each ligand was normalized to the striatal binding density. When compared to the striatal complex, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic binding sites had higher relative density in the globus pallidus, ventral pallidum, and subthalamic nucleus than other binding sites. Metabotropic binding also had a high relative density in the substantia nigra. Non-N-methyl-D-aspartate, non-kainate, non-quisqualate glutamate binding sites had a high relative density in globus pallidus, ventral pallidum, and substantia nigra. N-Methyl-D-aspartate binding sites had a low relative density in pallidum, subthalamic nucleus, substantia nigra and ventral tegmental area. Our data indicate heterogeneous distribution of excitatory amino acid binding sites within rat basal ganglia and suggest that the character of excitatory amino acid-mediated neurotransmission within the basal ganglia is also heterogeneous.     

Basal ganglia projections to the brain stem in the lizard Varanus exanthematicus as demonstrated by retrograde transport of horseradish peroxidase

In the present study the cells of origin of basal ganglia projections to the brain stem have been studied with the horseradish peroxidase technique in the lizard, Varanus exanthematicus. Injections of horseradish peroxidase were made at various levels of the brain stem from the mesodiencephalic border to the obex as well as in the tectum mesencephali. Efferent libers from the telencephalon to the diencephalon and the brain stem were found to arise predominantly from the striatum. From the present data it seems likely that the basal ganglia in Varanus exanthematicus as in other reptiles consist of two parts, a rostral ‘striatal’ part with projections mainly to the diencephalon and mesencephalon including the substantia nigra and a caudal ‘pallidal’ part with projections to the intercollicular nucleus and the rhombencephalic reticular formation.Injections of horseradish peroxidase into various parts of the rhombencephalic reticular formation have shown rather extensive projections from diencephalic and mesencephalic structures which receive afferents from the striatum: the posterior entopeduncular nucleus, the intercollicular nucleus and the substantia nigra were found to project as far caudal as the nucleus reticularis inferior. The substantia nigra shows, as regards its fiber connections, striking similarities to the mammalian substantia nigra, whereas the intercollicular nucleus possibly represents the reptilian homologue of the mammalian pedunculopontine nucleus.Injections of horseradish peroxidase into the tectum mesencephali have shown labeled cells in the nucleus of the posterior commissure, the posterior entopeduncular nucleus and the substantia nigra, all centers which are known to receive afferents from the striatum. Thus, the striatum can influence bisynaptically the reptilian homologue of the mammalian superior colliculus.It can be concluded that the striatum of the lizard, Varanus exanthematicus, has extensive direct as well as indirect projections to centers which influence the motor apparatus of the brain stem and spinal cord. Thus in reptiles it seems likely that the striatum exerts its influence on motor activity mainly via descending projections, in contrast to mammals where both descending and ascending striatal efferent pathways occur.     

多聚ADP-核糖聚合酶抑制剂对帕金森病小鼠相关脑区病理变化的影响

目的研究帕金森病(Park inson’s d isease,PD)小鼠黑质和纹状体多巴胺(dopam inergic,DA)能神经元数量和超微结构的变化及多聚ADP-核糖聚合酶(poly(ADP-ribose)polym erase,PARP)抑制剂PJ34的干预作用。方法采用1-甲基-4-苯-1,2,3,6-四氢吡啶(1-m ethyl-4-phenyl-1,2,3,6-tetrahydropyrid ine,MPTP)制备PD小鼠模型,并用PJ34进行干预,2h、24h、72h进行酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色观察DA能神经元数量,透射电镜观察超微结构改变。结果与正常对照小鼠比较,PD小鼠黑质TH阳性神经元进行性减少,核膜皱缩,染色质凝聚成块并有边聚现象;纹状体TH阳性神经纤维稀疏,突触数量减少。与PD小鼠比较,PJ34干预组黑质TH阳性神经元明显增多,纹状体TH阳性神经纤维密度增加(P<0.01),细胞形态比模型组明显改善。结论PARP的活性改变在PD的发病过程中发挥重要作用,PARP抑制剂对DA能神经元有保护作用。     

脑内主要神经核团三维空间的定位及其临床意义

目的：对脑内主要神经核团进行定位研究，为脑立体定向手术提供解剖学基础。方法：对１０２个整脑作三维切面的２ｍｍ厚连续切片，分别对８２个红核、黑质、丘脑底核，１１０个杏仁核、１２２个豆状核（壳核、苍白球）、丘脑和１１４个尾状核头等脑内主要神经核团进行定位研究。结果：各神经核团三轴“靶心”坐标值以及与大脑原点的位置关系。上述核团全部位于原点外，红核１００％位原点下、７６．８％位原点后，黑质１００％位原点下、６４．６％位原点前，丘脑底核１００％位原点下、４３．５％位原点前，杏仁核全部位原点前、下，壳核７６．６％位原点前、６９．２％位原位点，苍白球７６．１％位原点前、５８．９％位原点上，丘脑６１％位原点后、８９．５％位原点上，尾状核头１００％位原点前，８０％位原点上。结论：脑内主要神经核团的空间位置结果对脑的立体定向手术有参考价值     

Projections of the substantia nigra, ventral tegmental area and amygdala to the pallidum in dog brain

Using the method based on HRP retrograde axonal transport organization of projections of substantia nigra, tegmental ventral field and amygdala on pallidum was studied. Neuronal fibres from all dopaminergic portions of substantia nigra and tegmental ventral field were found to project on both structures of dog dorsal pallidum (globus pallidus and entopeduncular nucleus). Ventral pallidum receives projectional axons only from neurons of basal nucleus of amygdala and tegmental ventral field.