Neuronal localization of cannabinoid receptors in the basal ganglia of the rat

Cannabinoid receptors have recently been characterized and localized using a high-affinity radiolabeled cannabinoid analog in section binding assays. In rat brain, the highest receptor densities are in the globus pallidus and substantia nigra pars reticulata. Receptors are also dense in the caudate-putamen. In order to determine the neuronal localization of these receptors, selective lesions of key striatal afferent and efferent systems were made. Striatal neurons and efferent projections were selectively destroyed by unilateral infusion of ibotenic acid into the caudate-putamen. The nigrostriatal pathway was selectively destroyed in another set of animals by infusion of 6-hydroxydopamine into the medial forebrain bundle. After 2- or 4-week survivals, slide-mounted brain sections were incubated with ligands selective for cannabinoid ([3H]CP 55,940), dopamine D1 3H]SCH-23390) and D2 ([3H]raclopride) receptors, and dopamine uptake sites ([3H]GBR-12935). Slides were exposed to 3H-sensitive film. The resulting autoradiography showed ibotenate-induced losses of cannabinoid, D1 and D2 receptors in the caudate-putamen and topographic losses of cannabinoid and D1 receptors in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata at both survivals. Four weeks after medial forebrain bundle lesions (which resulted in amphetamine-induced rotations), there was loss of dopamine uptake sites in the striatum and substantia nigra pars compacta but no change in cannabinoid receptor binding. The data show that cannabinoid receptors in the basal ganglia are neuronally located on striatal projection neurons, including their axons and terminals. Cannabinoid receptors may be co-localized with D1 receptors on striatonigral neurons. Cannabinoid receptors are not localized on dopaminergic nigrostriatal cell bodies or terminals.     

Visualization of a dopamine D1 receptor mRNA in human and rat brain.

Using 32P-labeled oligonucleotides derived from the coding region of human dopamine D1 receptor mRNA we have localized in the human and rat brain the cells containing the mRNAs coding for this receptor. Dopamine D1 receptor mRNA in human brain was found to be contained in the neurons of the caudate and putamen nuclei as well as in the nucleus accumbens, some cortical regions and some nuclei of the amygdala. In the rat brain, cells containing D1 receptor mRNA were enriched in caudate-putamen and accumbens nuclei, olfactory tubercle, islands of Calleja, some cortical areas and in several thalamic nuclei. Moreover, in both species, it was absent from the neurons of the substantia nigra both pars compacta and pars reticulata and ventral tegmental area as well as from the globus pallidus pars lateralis and medialis in human and globus pallidus and entopeduncular nucleus in rat. In general, a good agreement was found with the distribution of binding sites labeled with the D1 antagonist SCH 23390. The main exception was the absence of D1 receptor mRNA in globus pallidus and substantia nigra, regions where high densities of receptor sites are found. These data support the notion that sites in these two regions are localized to projections from striatal neurons and that dopaminergic neurons do not express this receptor.     

Lesion Study of the Distribution of Serotonin 5-HT4 Receptors in Rat Basal Ganglia and Hippocampus

The regional distribution of 5-hydroxytryptamine (5-HT₄) receptors labelled with [³H]GR113808 was examined in rat basal ganglia and hippocampus after specific lesions. Lesion of serotonin neurons induced by injections of 5,7-dihydroxytryptamine into the dorsal and medial raphe nuclei resulted in increased 5-HT₄ receptor binding in most regions examined, compared with controls. More precisely, there was a 78% increase in the rostral but no change in the caudal part of caudate-putamen, and 83% and 54% increases in the shell and core of the nucleus accumbens respectively. In the substantia nigra, the increase in 5-HT₄ binding was larger (72%) than that in the globus pallidus (32%). In the hippocampus, 63%, 30% and 28% increases were measured in CA2, CA1 and CA3 respectively. Following lesion of dopamine neurons by intranigral injection of 6-hydroxydopamine, increased 5-HT₄ receptor binding was observed in the caudal (59%), but not the rostral part of caudate-putamen, as well as in the globus pallidus (93%). Since no decreases in 5-HT₄ receptor density were detected after the dopamine lesion, it was concluded that these receptors are not expressed in dopamine neurons. Kainic acid lesions of the caudate-putamen were associated with dramatic local decreases in 5-HT₄ receptor binding on the injected side (-89%), which suggested that striatal neurons express 5-HT₄ receptors. Corresponding decreases of 72 and 20% in receptor density were detected in globus pallidus and substantia nigra, consistent with a presumed localization of 5-HT₄ receptors on striatal GABA neurons projecting to these regions. In the substantia nigra, the decrease in [³H]GR113808 binding was localized to the pars lateralis, indicating that striatal neurons belonging to the cortico-striato-nigrotectal pathway, and containing GABA and dynorphin, express 5-HT₄ receptors.     

Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: immunohistochemical colocalization of the alpha 1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunits

The GABA(B) receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABA(B)R1 and GABA(B)R2. In this study, the cellular distribution of the GABA(B)R1 and GABA(B)R2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The results showed that the GABA(B) receptor subunits GABA(B)R1 and GABA(B)R2 were both found on the same neurons and followed the same distribution patterns. In the striatum, these subunits were found on the five major types of interneurons based on morphology and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the projection neurons (type 4). In the globus pallidus, intense GABA(B)R1 and GABA(B)R2 subunit labeling was found in large pallidal neurons, and in the substantia nigra, both pars compacta and pars reticulata neurons were labeled for both receptor subunits. Studies investigating the colocalization of the GABA(A) alpha(1) subunit and GABA(B) receptor subunits showed that the GABA(A) receptor alpha(1) subunit and the GABA(B)R1 subunit were found together on GABAergic striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD neurons) and on neurons in the globus pallidus and substantia nigra pars reticulata. GABA(B)R1 and GABA(B)R2 were found on substantia nigra pars compacta neurons but the GABA(A) receptor alpha(1) subunit was absent from these neurons. The results of this study provide the morphological basis for GABAergic transmission within the human basal ganglia and provides evidence that GABA acts through both GABA(A) and GABA(B) receptors. That is, GABA acts through GABA(B) receptors, which are located on most of the cell types of the striatum, globus pallidus, and substantia nigra. GABA also acts through GABA(A) receptors containing the alpha(1) subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata.     

5-HT2C receptor binding is increased in the substantia nigra pars reticulata in Parkinson's disease.

The involvement of abnormalities in nondopaminergic transmitter systems in Parkinson's disease is noteworthy because of the complications, such as dyskinesia, associated with long-term dopamine replacement therapy. The output regions of the basal ganglia, the substantia nigra pars reticulata, and the medial segment of the globus pallidus are overactive in Parkinson's disease but underactive in dyskinesia. 5-HT2C receptors are localized in these regions and are excitatory. A 5-HT2C receptor binding assay using [3H]-mesulergine and SB 200646A to define nonspecific binding was applied to postmortem tissue from patients with Parkinson's disease and from age-matched control patients. [3H]-mesulergine binding was increased in the substantia nigra pars reticulata by 108% in Parkinson's disease tissue as compared with control tissue. These data suggest abnormalities of 5-HT2C transmission in the basal ganglia of patients with Parkinson's disease.     

利用神经通路示踪方法证实大鼠纹状体神经元的连接

Using neural pathway tracing and immunohistochemical technique, the striato-direct pathway (BDA3 kDa injected into the rat lateral globus pallidus) and striato-indirect pathway (BDA3 kDa injected into the substantia nigra pars reticulata) neurons were specifically labeled, and then subjected to double-labeled immunohistochemistry for mu-OPIOID Receptor (specifically-labeled striatal patch compartment), D1, and D2, respectively. The experimental findings showed that there are no statistically significant differences in the soma diameter and the number of primary dendrites between the striato-direct (substantia nigra pars reticularis) and indirect (globus pallidum externum) neurons labeled retrograde by BDA3 kDa. In addition, these two kinds of projection neurons revealed no obvious coexistence. This evidence indicates that as a highly sensitive neural pathway tracer, BDA could yield reliably and exquisitely detailed labeling of target neurons and synaptic structures. The variance of the morphologic structures and the localization of neurons were not statistically significant between the striato-substantia nigra pars reticularis and the globus pallidum externum projection neurons. Mesencephalic and thalamic neurons correlated with striatal neurons in morphology. Especially the latter which make typical excitatory synaptic contacts with striato-direct and -indirect neurons. Thus, this evidence suggests that thalamic neurons may extensively excite striatal neurons.     

Calbindin-D28k in the basal ganglia of patients with parkinsonism.

An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D28k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin-D28k immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin-D28k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin-D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin-D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration.     

Axonal transport of dopamine D1 receptors in the rat brain

Binding of a specific dopamine D₁ receptor antagonist,¹²⁵I-SCH 23982, was measured in rat brain sections by quantitative autoradiography at various time intervals, following a knife cut through the striatonigral pathway. Twenty-four hours after lesioning, accumulations of D₁ receptor binding sites were found in sagittal sections both rostral and caudal to the lesion site. No other regions studied (caudate-putamen, nucleus accumbens, olfactory tubercle, and substantia nigra pars reticulata) showed any change in D₁ receptor binding 24h after the lesion. In brain sections obtained 10 days after lesioning, only the substantia nigra pars reticulata had a significant decrease in D₁ receptors ipsilateral to the lesion. These findings suggest the possibility of a presence of bidirectional axonal transport of D₁ receptors in rat striatonigral pathway.     

Differential expression of kainate receptors in the basal ganglia of the developing and adult rat brain

Glutamate is the principal excitatory transmitter of the mammalian brain and plays a particularly important role in the physiology of the basal ganglia structures responsible for movement regulation. Using in situ hybridization with oligonucleotide probes, we examined the expression patterns of the five known kainate type glutamate receptor subunit genes, KA1, KA2 and GluR5–7, in the basal ganglia of adult and developing rat brain. In the adult rat, a highly organized and selective pattern of expression of the kainate subunits was observed in the basal ganglia and associated structures as well as in other regions of the brain. KA2 mRNA was abundant in the striatum, nucleus accumbens, subthalamic nucleus and substantia nigra pars compacta, and was present at lower levels in the globus pallidus and substantia nigra pars reticulata. Neither KA1 nor GluR5 expression was observed in the basal ganglia of adult rats, although these messages were present in other regions. GluR6 was highly expressed in the striatum and subthalamic nucleus and to a lesser extent in the substantia nigra pars reticulata, while no hybridization signal was detectable in the large, presumably dopaminergic neurons of the substantia nigra pars compacta. In contrast, GluR7 was strongly expressed in the substantia nigra pars compacta, was present at lower levels in the striatum, globus pallidus and substantia nigra pars reticulata, and was not detectable in the subthalamic nucleus. During postnatal development, expression of the kainate receptor subunits was characteristically highest on postnatal day 1 and declined to adult levels by day 20; however, in the globus pallidus we did observe the transient expression of KA1 and GluR5 between day 1 and day 10. These results demonstrate that the neuronal structures comprising the basal ganglia express a distinct combination of kainate receptor subunit genes, suggesting that the pharmacological properties of the resultant glutamate receptors are likely to be regionally specific. The organization of expression of these genes is established early in life, which is consistent with the important role they may play in establishing the functions of the motor system.     

5-HT1B receptor binding in degenerative movement disorders

Using [³H]sumatriptan as a radioligand, 5-hydroxytryptamine (5-HT)_1B receptors were examined in posterior striatum and midbrain post-mortem tissue sections of 12 patients who had died from representative degenerative movement disorders as compared to nine controls. In the control human basal ganglia, the highest densities of [³H]sumatriptan binding were observed in the globus pallidus and substantia nigra. No significant change in the density of [³H]sumatriptan binding sites was found in the striatum and substantia nigra of the six Parkinson's disease brains. In the two brains from patients with progressive supranuclear palsy an increase was found in the densities of [³H]sumatriptan binding sites, most marked in the substantia nigra. In contrast, [³H]sumatriptan labelling was almost absent in the striatonigral degeneration brain and was markedly reduced in the three Huntington's disease brains. This study indicates that the status of 5-HT_1B receptors is different in each degenerative movement disorder and suggests that human 5-HT_1B receptors are located somatodendritically on GABAergic and peptidergic caudate-putamen neurons which project to the substantia nigra and globus pallidus, where these receptors are presynaptic.     

Expression of D4 dopamine receptors in striatonigral and striatopallidal neurons in the rat striatum

Recent studies have reported the regional distribution of D(4) dopamine receptors in the rat striatum at the cellular and subcellular levels. However, the precise identity of the striatal neurons that express these receptors remains unknown. We have studied the expression of D(4) receptors in the striatal interneurons as well as in the output regions of the striatum using immunohistochemistry. Furthermore, we have evaluated the contribution of the striatum to D(4) receptor immunoreactivity in these areas by means of ibotenic acid lesion of the striatum. D(4) receptors were observed in the substantia nigra pars reticulata (SNr), the entopeduncular nucleus (EP) and the globus pallidus (GP), and they were found, using electron microscopy, to be located presynaptically. D(4) immunoreactivity in the striatal output nuclei was observed to dramatically decrease following lesion of the striatum with ibotenic acid. Striatal interneurons were not found to express D(4) receptors. These results demonstrate that D(4) receptors are located almost exclusively in striatal projection neurons, in both striatonigral and striatopallidal neurons.     

Glycine receptors in the striatum, globus pallidus, and substantia nigra of the human brain: an immunohistochemical study

Glycine receptors (GlyRs) are heteropentameric chloride ion channels that facilitate fast-response, inhibitory neurotransmission in the mammalian spinal cord and brain. GlyRs have four functional subunits, alpha1-3 and beta, which likely exist in heteromeric alphabeta combinations. Mutations in GlyR alpha1 and beta subunits are well known for their involvement in hyperekplexia, a paroxysmal motor disorder. In this study we present the first detailed immunohistochemical investigation at the regional, cellular, and subcellular levels of GlyRs in the human basal ganglia. The results show that GlyRs are present at the regional level in low concentrations in the striatum and globus pallidus and are present in the highest concentrations in the substantia nigra. At the cellular level, GlyRs are present only in discrete populations of neurons immunoreactive for choline acetyltransferase (ChAT), parvalbumin, and calretinin in the human striatum, on a subpopulation of parvalbumin- and calretinin-positive neurons in the globus pallidus, and in the substantia nigra GlyRs are present on approximately three-fourths of all pars compacta and one-third of all pars reticulata neurons. They also form a distinct band of immunoreactive neurons in the intermedullary layers of the globus pallidus. At the subcellular level in the substantia nigra pars reticulata (SNr), GlyRs show a localized distribution on the soma and dendrites that partially complements but does not overlap with the distribution of gamma-aminobutyric acid (GABA)A receptors. Our results demonstrate the precise cellular and subcellular localization of GlyRs in the human basal ganglia and suggest that glycinergic receptors may play an important complementary role to other inhibitory receptors in modulating cholinergic, dopaminergic, and GABAergic neuronal pathways in the basal ganglia.     

Substantia nigra opiate receptors on basal ganglia efferents

Many behavioral effects of opiate narcotics and peptides have been linked to effects on dopamine neurons originating in the substantia nigra pars compacta and ventral tegmental area. Selective brain lesions were combined with quantitative autoradiography to determine whether opiate receptors are on dopaminergic somata and/or processes in the substantia nigra pars compacta and ventral tegmental area. 6-Hydroxydopamine lesions that eliminated dopamine neurons produced little change in the pattern or density of [³H]-naloxone binding in the substantia nigra pars compacta or ventral tegmental area. Radiofrequency lesions of the internal capsule or globus pallidus and kainic acid lesions of the striatum markedly decreased [³H]-naloxone binding in the pars compacta and pars reticulata. These results are consistent with a dense distribution of opiate receptors on pallido-nigral and/or striato-nigral fibers and strengthen the likelihood that local effects of opiates on dopamine function in the nigrostriatal pathway are mediated indirectly by actions on nondopaminergic processes.     

Stability of substantia nigra pars reticulata neuronal discharge rates during dopamine receptor blockade and its possible mechanisms

It is hypothesized that substantia nigra pars reticulata neurons become overactive during a deficit of dopamine transmission. In this study, we examined how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse activity of substantia nigra pars reticulata neurons and their response to iontophoretic gamma-amino-n-butyric acid in awake, unrestrained rats. No changes in discharge rate were found during complete dopamine receptor blockade, but these neurons showed a diminished response to gamma-amino-n-butyric acid, suggesting gamma-amino-n-butyric acid receptor hyposensitivity. This may result from tonic increase in gamma-amino-n-butyric acid input from the striatum and globus pallidus, which are activated during dopamine receptor blockade. As substantia nigra pars reticulata neurons are autoactive and resistant to tonic increases in gamma-amino-n-butyric acid input, changes in their responsiveness to phasic gamma-amino-n-butyric acid inputs, not tonic increase discharge rate, may underlie movement disturbance following dopamine deficit.     

Pattern of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats

The distribution of the serotonin (5-HT) receptor 5-HT_2C mRNA was examined at the single-cell level with in situ hybridization histochemistry and emulsion autoradiography in the basal ganglia and mesolimbic system of adult rats, with focus on the pallidum and the substantia nigra, which receive striatal inputs and play a critical role in basal ganglia function. 5-HT_2C receptor mRNA expression was always restricted to a subpopulation of neurons in the regions examined. In the neostriatum, labeled neurons were more numerous in the rostral nucleus accumbens than in the caudal nucleus accumbens and were more numerous in the ventral and ventrolateral caudate-putamen than in the dorsal caudate-putamen, where labeled neurons were restricted to isolated clusters. In striatal target areas, dense labeling in the entopeduncular nucleus (internal pallidum, direct striatal output pathway) contrasted with an absence of labeling in the globus pallidus (external pallidum, indirect striatal output pathway). Double-label in situ hybridization in the substantia nigra revealed coexpression of 5-HT_2C receptor mRNA with glutamic acid decarboxylase but not with tyrosine hydroxylase mRNA, indicating that it was restricted to γ-aminobutyric acid (GABA)ergic neurons. In this region, dense labeling for 5-HT_2C mRNA was found in half of the neurons at middle and caudal levels of both the pars compacta and the pars reticulata, with little labeling rostrally. The data suggest that drugs acting on the 5-HT_2C receptor could selectively affect discrete neuronal populations in the basal ganglia and mesolimbic systems and indicate a new level of neurochemical heterogeneity among GABAergic neurons of the substantia nigra. J. Comp. Neurol. 384:233-247, 1997. © 1997 Wiley-Liss, Inc.     

The functional role of the nucleus accumbens in the control of the substantia nigra: Electrophysiological investigations in intact and striatum-globus pallidus lesioned rats

The effects of electrical stimulation of the nucleus accumbens on the activity of identified substantia nigra neurons were studied in intact and lesioned rats. The latter had both the caudate-putamen complex and globus pallidus destroyed by electrolytic lesions. In intact rats a total of 42 of 107 neurons (39.2%) responded to stimulation of the nucleus accumbens. Of the 107 neurons 32 (29.8%) were inhibited and 10 (9.4%) were excited. Pure short inhibitions, long latency inhibitions and excitations followed by inhibition were found in both parts of the substantia nigra. Pure long lasting inhibitions were determined on pars compacta cells only. In lesioned animals, in which the coactivation of striatal and/or cortical fibers traversing the accumbens region was avoided, the percentage of responsive neurons decreased to 20% (23/115). The predominant responses recorded in this situation were pure inhibitions of pars compacta cells (14/46) and long latency inhibitions of pars reticulata neurons (7/69). No pure excitation or excitation-inhibition sequence was recorded. In the two sets of experiments 5 cells were activated antidromically from the nucleus accumbens. The results provide electrophysiological evidence for an inhibitory pathway from the nucleus accumbens to the substantia nigra. The low percentage of responsive neurons, the lack of excitatory responses, the paucity of reciprocal connections and the different inhibitory effects on the two populations of nigral neurons demonstrate that the functional role of the nucleus accumbens in controlling the substantia nigra differs from that exerted by the striatum.     

Involvement of the direct striatonigral pathway in levodopa-induced sensitization in 6-hydroxydopamine-lesioned rats

Induction of dopamine D3 receptor gene expression in 6-hydroxydopamine-lesioned rats by repeated administration of levodopa had been suggested to be responsible for behavioural sensitization developing in these animals. Using double in situ hybridization techniques, we show that D3 receptor mRNA induction after repeated administration of levodopa took place mainly in dynorphin/substance P-expressing neurons of the direct striatonigral pathway. In agreement, induction of D3 receptor binding sites was evidenced, using 7-[3H]hydroxy-N,N-di-propyl-2-aminotetralin ([3H]7-OH-DPAT), in substantia nigra pars reticulata, the projection area of the direct nigrostriatonigral pathway. Changes in D3 receptor binding and behavioural sensitization during intermittent administration of levodopa paralleled changes in prodynorphin/preprotachykinin rather than preproenkephalin/prodynorphin and preproenkephalin/preprotachykinin mRNA ratios. Behavioural sensitization, induction of D3 receptor binding and changes in prodynorphin/preprotachykinin ratio were all prevented together when levodopa was continuously delivered or intermittently delivered in combination with R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH 23390), a selective D1 receptor antagonist. Our results indicate that functional changes of the direct striatal output pathway, possibly through an interaction between D1 and D3 receptors at the level of terminals in the substantia nigra pars reticulata, are important for the development of behavioural sensitization.     

Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia

Metabotropic glutamate receptors (mGluRs), which couple glutamate to second messengers, have important roles in the regulation of movement by the basal ganglia. We used two polyclonal antisera to mGluR1a and mGluR2/3 and confocal laser microscopy to investigate the localization of these receptors in the basal ganglia of the rat. The mGluRs were visualized in combination with an antibody to tyrosine hydroxylase (TH), an antibody to microtubule-associated protein 2 (MAP2, a dendritic marker), or SV2 (an antibody to a protein associated with presynaptic terminals). In the neostriatum, punctate mGluR1a immunoreactivity (ir) was present in the neuropil. This staining did not colocalize with MAP2-ir or SV2-ir and was not altered by decortication or unilateral 6-hydroxydopamine (6-OHDA) lesions. In the globus pallidus and substantia nigra pars reticulata, however, mGluR1a-ir was tightly clustered along large MAP2-ir dendrites. In contrast to the variations in mGluR1a-ir staining, similar punctate neuropil mGluR2/3-ir staining was observed within all basal ganglia structures. In the neostriatum, these puncta were abundant; unlike mGluR1a, many mGluR2/3-ir puncta colocalized with SV2-ir, and striatal mGluR2/3-ir puncta were markedly reduced in number after decortication. Neither mGluR1a-ir nor mGluR2/3-ir could be detected in TH-ir soma within substantia nigra pars compacta, or in TH-ir striatal terminals. Overall, our observations suggest that mGluR1a and mGluR2/3 receptors have distinct cellular localizations in different components of the basal ganglia circuitry and are likely to subserve distinct functions. Our data support the presence of mGluR2/3 on the terminals of corticostriatal afferents, where they may regulate glutamate release. In contrast, mGluR1a appears to be a postsynaptic receptor of neurons in the neostriatum, globus pallidus, and substantia nigra pars reticulata. J. Comp. Neurol. 390:5–19, 1998. © 1998 Wiley-Liss, Inc.     

左旋多巴诱发异动症大鼠模型基底节区谷氨酸脱羧酶表达的研究

目的 研究左旋多巴诱发异动症(LID)大鼠模型尾壳核、苍白球及黑质网状部谷氨酸脱羧酶(GAD)表达的变化。方法用免疫组织化学方法观测大鼠尾壳核、苍白球及黑质网状部GAD的表达变化，用辣根过氧化物酶(HRP)逆行示踪与免疫组织化学相结合的双重反应技术观测GAD的细胞分布状况。结果 LID大鼠较正常及非LID大鼠尾壳核区GAD明显增加，尤其在尾壳核外侧区增加更明显，且主要分布在纹状体黑质神经元内，苍白球区GAD明显增加，而黑质网状部GAD减少。结论 大鼠基底节区GAD表达变化与LID的发生有关，直接通路活动异常及基底节环路功能异常参与大鼠LID的发生。