Dopaminergic innervation of human basal ganglia

This paper summarises the results of some of our recent tyrosine hydroxylase (TH) immunohistochemical studies of the dopaminergic innervation of the human basal ganglia. It also reports new findings on the presence of TH-immunoreactive (ir) neurons in the striatum. Our data show the existence of nigrostriatal TH-ir axons that provide collaterals arborizing in the globus pallidus and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson's pencils. We postulate that this extrastriatal innervation, which allows nigral dopaminergic neurons to directly affect the pallidum and subthalamic nucleus, plays a critical role in the functional organisation of human basal ganglia. The TH-ir fibres that reach the striatum arborize according to a highly heterogeneous pattern. At rostral striatal levels, numerous small TH-poor zones embedded in a TH-rich matrix correspond to calbindin-poor striosomes and calbindin-rich extrastriosomal matrix, respectively. At caudal striatal levels, in contrast, striosomes display a TH immunostaining that is more intense than that of the matrix. A significant number of small, oval, aspiny TH-ir neurons scattered throughout the rostrocaudal extent of the caudate nucleus and putamen, together with a few larger, multipolar, spiny TH-ir neurons lying principally within the ventral portion of the putamen, were disclosed in human. This potential source of intrinsic striatal dopamine might play an important role in the functional organisation of the human striatum, particularly in case of Parkinson's disease.     

Monoaminergic innervation of the macaque extended amygdala.

The extended amygdala is a group of structures including the central and medial amygdaloid nuclei, bed nucleus of the stria terminalis, and sublenticular substantia innominata. This group of structures is thought to be important in a variety of psychiatric disorders, many of which are linked in one way or another to monoamines and their transporters. However, not much is known about the distribution of these molecules in the primate extended amygdala. Thus, we mapped the distribution of fibers immunoreactive for tyrosine hydroxylase, dopamine beta-hydroxylase, serotonin, dopamine transporter, and serotonin transporter in the brains of macaque monkeys.Tyrosine hydroxylase-, serotonin-, and serotonin transporter-immunoreactive fibers were found in highest concentrations in the lateral division of the central nucleus and lateral dorsal part of the bed nucleus of the stria terminalis. Dopamine beta-hydroxylase-immunoreactive fibers were found in the highest concentration in the lateral ventral bed nucleus of the stria terminalis. Dopamine transporter-immunoreactive fibers were found in the highest concentrations in the lateral juxtacapsular and lateral dorsal capsular subnuclei of the bed nucleus and lateral capsular subnucleus of the central amygdaloid nucleus, though in much lower amounts than was present in the striatum.These results suggest prominent roles for these transmitters, particularly in the lateral dorsal bed nucleus and lateral part of the central nucleus. The relative absence of dopamine transporter in the extended amygdala suggests that this transmitter acts more through volume transmission while serotonin, which is generally accompanied by proportionate amounts of transporter, may act more like a classical neurotransmitter. In addition, the finding of heavy concentrations of dopamine- and serotonin-immunoreactive fibers in the lateral central nucleus and lateral dorsal bed nucleus lends further support to the idea of these areas as parallels in some respects to the striatum.     

Serotonin innervation of basal ganglia in monkeys and humans

This review paper summarizes our previous contributions to the study of serotonin (5-hydroxytryptamine; 5-HT) innervation of basal ganglia in human and nonhuman primates under normal conditions. We have visualized the 5-HT neuronal system in squirrel monkey (Saimiri sciureus) and human postmortem materials with antibodies directed against either 5-HT, 5-HT transporter (SERT) or 5-HT synthesizing enzyme tryptophan hydroxylase (TPH). Confocal microscopy was used to compare the distribution of 5-HT and dopamine (DA; tyrosine hydroxylase-immunolabeled) axons in human, while the ultrastructural features of 5-HT axon terminals in monkey subthalamic nucleus were characterized at electron microscopic level. In monkeys and humans, midbrain raphe neurons emit axons that traverse the brainstem via the transtegmental system, ascend within the medial forebrain bundle and reach their targets by coursing along the major output pathways of the basal ganglia. These 5-HT axons arborize in virtually all basal ganglia components with the substantia nigra receiving the densest innervation and the striatum the most heterogeneous one. Although the striatum - the major basal ganglia input structure - appears to be a common termination site for many of 5-HT ascending axons, our results reveal that the widely distributed 5-HT neuronal system can also act directly upon neurons located within the two major output structures of the basal ganglia, namely the internal pallidum and the substantia nigra pars reticulata in monkeys and humans. This system also has a direct access to neurons of the DA nigrostriatal pathway, a finding that underlines the importance of the 5-HT/DA interactions in the physiopathology of basal ganglia.     

Extrastriatal dopaminergic innervation of human basal ganglia.

A tyrosine-hydroxylase immunohistochemical analysis of the brains of normal human individuals has revealed nigrostriatal axons providing collaterals that arborize in the pallidum and subthalamic nucleus. These thin and varicose collaterals emerge from thick and smooth axons that course backward along the main output pathways of the basal ganglia, including the ansa lenticularis, the lenticular fasciculus and Wilson's pencils. Many of these fibers run within pallidal medullary laminae before reaching the putamen, whereas others climb along the reticular thalamic nucleus to reach the caudate nucleus. This extrastriatal innervation, which allows nigral dopaminergic neurons to directly affect the pallidum and subthalamic nucleus, may play a crucial role in the functional organization of human basal ganglia, in both health and disease.     

Dopaminergic innervation of interneurons in the rat basolateral amygdala

The basolateral nuclear complex of the amygdala (BLC) receives a dense dopaminergic innervation that plays a critical role in the formation of emotional memory. Dopamine has been shown to influence the activity of BLC GABAergic interneurons, which differentially control the activity of pyramidal cells. However, little is known about how dopaminergic inputs interface with different interneuronal subpopulations in this region. To address this question, dual-labeling immunohistochemical techniques were used at the light and electron microscopic levels to examine inputs from tyrosine hydroxylase-immunoreactive (TH+) dopaminergic terminals to two different interneuronal populations in the rat basolateral nucleus labeled using antibodies to parvalbumin (PV) or calretinin (CR). The basolateral nucleus exhibited a dense innervation by TH+ axons. Partial serial section reconstruction of TH+ terminals found that at least 43-50% of these terminals formed synaptic junctions in the basolateral nucleus. All of the synapses examined were symmetrical. In both TH/PV and TH/CR preparations the main targets of TH+ terminals were spines and distal dendrites of unlabeled cells. In sections dual-labeled for TH/PV 59% of the contacts of TH+ terminals with PV+ neurons were synapses, whereas in sections dual-labeled for TH/CR only 13% of the contacts of TH+ terminals with CR+ cells were synapses. In separate preparations examined in complete serial sections for TH+ basket-like innervation of PV+ perikarya, most (76.2%) of TH+ terminal contacts with PV+ perikarya were synapses. These findings suggest that PV+ interneurons, but not CR+ interneurons, are prominent synaptic targets of dopaminergic terminals in the BLC.     

Dopaminergic innervation of pyramidal cells in the rat basolateral amygdala

Dopaminergic (DA) inputs to the basolateral nuclear complex of the amygdala (BLC) are critical for several important functions, including reward-related learning, drug-stimulus learning, and fear conditioning. Despite the importance of the DA projection to the BLC, very little is known about which neuronal subpopulations are innervated. The present study utilized dual-labeling immunohistochemistry at the electron microscopic level to examine DA inputs to pyramidal cells in the anterior basolateral amygdalar nucleus (BLa) in the rat. DA axon terminals and BLa pyramidal cells were labeled using antibodies to tyrosine hydroxylase (TH) and calcium/calmodulin-dependent protein kinase II (CaMK), respectively. Serial section reconstructions of TH-positive (TH+) terminals were performed to determine the extent to which these axon terminals formed synapses versus non-synaptic appositions in the BLa. Our results demonstrate that at least 77% of TH+ terminals form synapses in the BLa, and that 90% of these synapses are with pyramidal cells. The distal dendritic compartment received the great majority of these synaptic contacts, with CaMK+ distal dendrites and spines receiving one-third and one-half, respectively, of all synaptic inputs to pyramidal cells. Many spines receiving innervation from TH+ terminals also received asymmetrical synaptic inputs from putative excitatory terminals. In addition, TH+ terminals often formed non-synaptic appositions with axon terminals, most of which were putatively excitatory in that they were CaMK+ and/or made asymmetrical synapses. Thus, using CaMK as a marker, the present study demonstrates that pyramidal cells, especially their distal dendritic compartments, are the primary targets of dopaminergic inputs to the basolateral amygdala.     

Environmental context and drug history modulate amphetamine-induced c-fos mRNA expression in the basal ganglia,central extended amygdala,and associated limbic forebrain

The context in which amphetamine is administered modulates its ability to induce both behavioral sensitization and immediate early gene expression. When given in a novel test environment amphetamine produces greater levels of c-fos and arc mRNA expression in many brain regions relative to when it is given in the home cage. The purpose of the current study was to determine if environment and drug history interact to influence amphetamine-induced c-fos mRNA expression. Rats with a unilateral 6-hydroxydopamine lesion were treated for 7 days with saline or 0.5 mg/kg of d-amphetamine (i.v.) in a distinct and relatively novel test environment (Novel), or in their home cage (Home). Following a 10-12-day withdrawal period, a challenge injection of either saline or 0.5 mg/kg d-amphetamine was administered. In situ hybridization histochemistry was used to examine c-fos mRNA expression in several regions of the basal ganglia, the central extended amygdala, and limbic forebrain. In most brain regions amphetamine given in the Novel environment produced greater c-fos mRNA expression than when given it was given at Home, and drug history had no effect on amphetamine-induced c-fos mRNA expression. However, within the subthalamic nucleus, substantia nigra reticulata, and central nucleus of the amygdala prior experience with amphetamine in the Novel but not Home environment enhanced the effect of an amphetamine challenge injection on c-fos mRNA expression. In contrast, there was a decrease in c-fos mRNA expression in amphetamine-pretreated animals, regardless of environmental context, in the ventral portion of the far caudal striatum. Reexposure to an environment previously paired with amphetamine produced a conditioned increase in c-fos mRNA expression in portions of the caudate-putamen, the subthalamic nucleus, the nucleus accumbens shell and a conditioned decrease in c-fos mRNA expression in the central nucleus of the amygdala. We conclude that environmental context and drug history interact to alter the basal ganglia and central extended amygdala circuitry engaged by subsequent exposure to amphetamine, or exposure to an environment previously paired with amphetamine.     

Reduced basal GABA concentrations in the rat amygdala during pregnancy

Marked increases in anxiety-like responses to stress occur during pregnancy. Considerable evidence indicates that the basolateral region of the amygdala (BLA) plays an important role in mediating these types of responses. Given the crucial inhibitory influence of GABA on excitatory glutamatergic activity in the BLA, we hypothesized that decreased GABAergic activity in this region may underlie the increased anxiety associated with pregnancy. In vivo microdialysis was used to sample extracellular GABA before and after 30 min of restraint stress. While there was no detectable effect of restraint on extracellular GABA concentrations, basal GABA levels were significantly decreased in pregnant rats compared with either virgin females or males. We suggest that the alterations in anxiety-like behavior that occur during pregnancy may be associated with decreased basal GABA in the BLA.     

Distribution of somatostatin immunoreactivity in the forebrain of the squirrel monkey: basal ganglia and amygdala.

The distribution of somatostatin immunoreactivity in the basal ganglia and amygdala of the squirrel monkey (Saimiri sciureus) was studied with specific polyclonal antibodies directed against somatostatin-28 and somatostatin-28(1-12). Both antibodies gave similar results with regard to the distribution of somatostatin-immunoreactive neuronal profiles. A moderately dense and highly heterogeneous network of somatostatin-positive fibers was observed throughout the striatum. A dorsoventral gradient of increasing immunoreactivity was noted in the striatum and the caudate nucleus was found to strain generally less intensely than the putamen. The immunoreactive fibers within the striatum were mostly thin and varicose and formed patches corresponding to the striosomes, as visualized on adjacent sections immunostained for calbindin. Although some somatostatin cell bodies rimmed the striosomes, most of the positive cells were rather uniformly scattered in the striatum. These medium-sized cells were significantly smaller in the caudate nucleus (93 microns2, S.D. = 26 microns2) than in the putamen (122 microns2, S.D. = 39 microns2), but their density was significantly higher in the caudate nucleus (29.7 cells/mm2, S.D. = 8.8 cells/mm2) than in the putamen (20.5 cells/mm2, S.D. = 7.0 cells/mm2). The nucleus accumbens stained moderately and positive cell bodies were evenly dispersed throughout this structure. In contrast, the olfactory tubercle displayed a heavily stained neuropil but positive neurons were encountered only in its polymorph layer. In the sublenticular region, dense fiber plexuses appeared in register with nonreactive cell clusters of the nucleus basalis of Meynert and of the nucleus of the anterior commissure. More caudally, a dense bundle of positive fibers was observed at the level of the ansa lenticularis, the inferior thalamic peduncle, and the adjoining bed nucleus of the stria terminalis. Several fibers contributing to this bundle were of the woolly type. Woolly fibers also coursed in the substantia innominata between the ventral aspect of the globus pallidus and the optic tract, and ascended in the internal medullary lamina separating the internal and external segments of the globus pallidus. Somatostatin-immunoreactive cell bodies were uniformly scattered throughout the substantia innominata. The various nuclei of the amygdala showed a wide range of immunoreactivity. The central nucleus was lightly reactive, whereas the intercalated masses displayed a moderate staining. A dorsoventral gradient of immunostaining was noted in the ventrolateral portion of the amygdala, the lateral nucleus being moderately to densely stained and the basal nucleus very lightly to lightly immunoreactive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term plastic changes in galanin innervation in the rat basal forebrain

Galanin immunoreactive fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease, perhaps exacerbating the cholinergic deficit. The purpose of our study is to determine whether a similar phenomenon occurs following intraparenchymal injection of 192 IgG-saporin, a specific cholinergic neurotoxin, within the nucleus of the horizontal limb of the diagonal band of Broca. Immunotoxic lesion produced on average a 31% reduction in cholinergic cell counts ipsilateral to the lesion, compared to the contralateral side. Increased galanin immunoreactivity, suggestive of increased fiber density, was observed within and adjacent to the lesion in 28 out of 36 rats, and this effect persisted across time up to 6 months (the longest time examined). We observed a parallel increase in the number of galanin positive neurons ipsilateral to the lesion, compared to the contralateral side. No correlative change could be detected in the number of galaninergic neurons in the amygdala or the bed nucleus of the stria terminalis. There was no statistically significant correlation between the extent of cholinergic cell loss and the increase in galanin immunoreactivity surrounding the lesion. Yet, since both of these changes persist over time, we suggest that galanin plasticity is triggered by neuronal damage. Our model can be useful to test the role that galanin plays in the regulation of acetylcholine and the efficacy of galanin inhibitors as potential therapeutic interventions in Alzheimer's disease.     

Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia

Endocannabinoids, acting via type 1 cannabinoid receptors (CB1), are known to be involved in short-term synaptic plasticity via retrograde signaling. Strong depolarization of the postsynaptic neurons is followed by the endocannabinoid-mediated activation of presynaptic CB1 receptors, which suppresses GABA and/or glutamate release. This phenomenon is termed depolarization-induced suppression of inhibition (DSI) or excitation (DSE), respectively. Although both phenomena have been reported to be present in the basal ganglia, the anatomical substrate for these actions has not been clearly identified. Here we investigate the high-resolution subcellular localization of CB1 receptors in the nucleus accumbens, striatum, globus pallidus and substantia nigra, as well as in the internal capsule, where the striato-nigral and pallido-nigral pathways are located. In all examined nuclei of the basal ganglia, we found that CB1 receptors were located on the membrane of axon terminals and preterminal axons. Electron microscopic examination revealed that the majority of these axon terminals were GABAergic, giving rise to mostly symmetrical synapses. Interestingly, preterminal axons showed far more intense staining for CB1, especially in the globus pallidus and substantia nigra, whereas their terminals were only faintly stained. Non-varicose, thin unmyelinated fibers in the internal capsule also showed strong CB1-labeling, and were embedded in bundles of myelinated CB1-negative axons. The majority of CB1 receptors labeled by immunogold particles were located in the axonal plasma membrane (92.3%), apparently capable of signaling cannabinoid actions. CB1 receptors in this location cannot directly modulate transmitter release, because the release sites are several hundred micrometers away. Interestingly, both the CB1 agonist, WIN55,212-2, as well as its antagonist, AM251, were able to block action potential generation, but via a CB1 independent mechanism, since the effects remained intact in CB1 knockout animals. Thus, our electrophysiological data suggest that these receptors are unable to influence action potential propagation, thus they may not be functional at these sites, but are likely being transported to the terminal fields. The present data are consistent with a role of endocannabinoids in the control of GABA, but not glutamate, release in the basal ganglia via presynaptic CB1 receptors, but also call the attention to possible non-CB1-mediated effects of widely used cannabinoid ligands on action potential generation.     

Atrial natriuretic factor in sympathetic ganglia of the rat: dependence on cholinergic innervation

Atrial natriuretic factor is detectable in the peripheral autonomic ganglia of the rat by radioimmunoassay and immunohistochemistry. In the present study, surgical and neurochemical methods were used to evaluate the source of this peptide in sympathetic ganglia. Decentralization of the ganglia and/or central administration of colchicine diminished the atrial natriuretic factor content in para- and prevertebral ganglia. Axotomy did not affect levels of ganglionic atrial natriuretic factor. A messenger ribonucleic acid species hybridizing with rat atrial natriuretic factor complementary deoxyribonucleic acid was not found within the total ribonucleic acid extracted from superior cervical ganglia. These results indicate a direct dependence of ganglionic atrial natriuretic factor on cholinergic innervation.     

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

The dorsal raphe nucleus (DRN) contains both serotonergic and nonserotonergic projection neurons. Retrograde tracing studies have demonstrated that components of the basal forebrain and extended amygdala are targeted heavily by input from nonserotonergic DRN neurons. The object of this investigation was to examine the terminal distribution of nonserotonergic DRN projections in the basal forebrain and extended amygdala, using a technique that allows selective anterograde tracing of nonserotonergic DRN projections. To trace nonserotonergic DRN projections, animals were pretreated with nomifensine, desipramine and the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), 7 days prior to placing an iontophoretic injection of biotinylated dextran amine (BDA) into the DRN. In animals treated with 5,7-DHT, numerous nonserotonergic BDA-labeled fibers ascended to the basal forebrain in the medial forebrain bundle system. Some of these labeled fibers crossed through the lateral hypothalamus, bed nucleus of the stria terminalis, and substantial innominata. These fibers entered the amygdala through the ansa peduncularis and ramified within the central and basolateral amygdaloid nuclei. Other fibers entered the diagonal band of Broca and formed a dense plexus of labeled fibers in the dorsal half of the intermediate portion of the lateral septal nucleus and the septohippocampal nucleus. These findings demonstrate that the basal forebrain and extended amygdala receive a dense projection from nonserotonergic DRN neurons. Given that the basal forebrain plays a critical role in processes such as motivation, affect, and behavioral control, these findings support the hypothesis that nonserotonergic DRN projections may exert substantial modulatory control over emotional and motivational functions.     

NMDA receptors in the basal ganglia

The basal ganglia consist of several interconnected nuclei located in the telecephalon, diencephalon and mesencephalon that are involved in a variety of motor and non-motor behavioural functions. Glutamate receptors play a major role in neurotransmission within the basal ganglia and are present in all nuclei of the basal ganglia. This review focuses on the contribution of the NMDA class of glutamatergic receptors to various movement disorders whose primary pathology lies within the basal ganglia and discusses how pharmacological manipulation of such receptors may be therapeutically useful.     

Parvalbumin-immunoreactive neurons and GABAergic neurons of the basal forebrain project to the rat basolateral amygdala

The basal forebrain (BF) contains a diffuse array of cholinergic and non-cholinergic neurons that project to the cerebral cortex and basolateral nuclear complex of the amygdala (BLC). Previous studies have shown that the GABAergic subpopulation of non-cholinergic corticopetal BF neurons selectively innervates cortical interneurons. Although several investigations in both rodents and primates have indicated that some BF neurons projecting to the BLC are non-cholinergic, there have been no studies that have attempted to identify the neurochemical phenotype(s) of these neurons. The present study combined Fluorogold retrograde tract tracing with immunohistochemistry for two markers of BF GABAergic neurons, parvalbumin (PV) or glutamic acid decarboxylase (GAD), to determine if a subpopulation of BF GABAergic cells projects to the BLC. Injections of Fluorogold confined to the rat BLC, and centered in the basolateral nucleus, produced extensive retrograde labeling in the ventral pallidum and substantia innominata regions of the BF. Although the great majority of retrogradely labeled neurons were not double-labeled, about 10% of these neurons, located mainly along the ventral aspects of the fundus striati and globus pallidus, exhibited immunoreactivity for PV or GAD. The results of this investigation contradict the long-held belief that there is no extra-amygdalar source of GABAergic inputs to the BLC, and indicate that the cortex-like BLC, in addition to the cortex proper, receives inhibitory inputs from the basal forebrain.     

Brain state-dependency of coherent oscillatory activity in the cerebral cortex and basal ganglia of the rat

The nature of the coupling between neuronal assemblies in the cerebral cortex and basal ganglia (BG) is poorly understood. We tested the hypothesis that coherent population activity is dependent on brain state, frequency range, and/or BG nucleus using data from simultaneous recordings of electrocorticogram (ECoG) and BG local field potentials (LFPs) in anesthetized rats. The coherence between ECoG and LFPs simultaneously recorded from subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNr) was largely confined to slow- ( approximately 1 Hz) and spindle- (7-12 Hz) frequency oscillations during slow-wave activity (SWA). In contrast, during cortical activation, coherence was mostly restricted to high-frequency oscillations (15-60 Hz). The coherence between ECoG and LFPs also depended on BG recording site. Partial coherence analyses showed that, during SWA, STN and SNr shared the same temporal coupling with cortex, thereby forming a single functional axis. Cortex was also tightly, but independently, correlated with GP in a separate functional axis. During activation, STN, GP, and, to a lesser extent, SNr shared the same coherence with cortex as part of one functional axis. In addition, GP formed a second, independently coherent loop with cortex. These data suggest that coherent oscillatory activity is present at the level of LFPs recorded in cortico-basal ganglia circuits, and that synchronized population activity is dynamically organized according to brain state, frequency, and nucleus. These attributes further suggest that synchronized activity should be considered as one of a number of candidate mechanisms underlying the functional organization of these brain circuits.     

Synaptic organisation of the basal ganglia

The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context‐dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is ‘processed’ within the striatum and passed via the so‐called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical ‘premotor’ regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed‐forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic integration of functionally diverse information derived from the cortex. It is concluded that the essential concept of the direct and indirect pathways of information flow through the basal ganglia remains intact but that the role of the indirect pathway is more complex than previously suggested and that neurons of the globus pallidus are in a position to control the activity of virtually the whole of the basal ganglia.     

基底神经节的认知功能

长期以来,人们一直认为基底神经节的功能与运动的起始与调控有关,其损伤或病变主要表现为运动方面的症状,如帕金森病、亨廷顿舞蹈症、肝豆状核变性、手足徐动症等.但是随着神经科学,尤其是神经解剖学的发展,基底神经节的皮质下区联系环路逐步被确定.另外,大量的临床实践证实基底神经节与包括言语障碍、记忆障碍、情绪认知和情绪障碍、智能障碍和痴呆等认知功能障碍密切相关川.目前人们对基底神经节的功能,尤其是它与认知功能的关系尚未有清晰的认识.本文拟对基底神经节的认知功能做一综述.