Activity In Putamen Research Articles

Cholinergic vesicular transporters in progressive supranuclear palsy.

To determine the status of cholinergic and monoaminergic vesicular transporter binding sites in progressive supranuclear palsy (PSP). The authors determined autoradiographically the regional expression of acetylcholine vesicular transporter (VAChT) and monoamine vesicular transporter type 2 (VMAT2) binding sites in postmortem basal ganglia samples from subjects with PSP. Comparison neurochemical measures included choline acetyltransferase (ChAT) enzyme activity and benzodiazepine (BZ) binding sites. VAChT expressions and ChAT activities in caudate nucleus and putamen were markedly decreased in PSP, whereas BZ binding was unaffected, consistent with selective losses of striatal cholinergic interneurons. VMAT2 density was reduced significantly in the caudate nucleus, putamen, and substantia nigra pars compacta, consistent with degeneration of dopaminergic nigrostriatal projection neurons in PSP. In the globus pallidus, BZ receptor binding sites were reduced, whereas VMAT2 and VAChT binding sites were unchanged, indicating losses of intrinsic pallidal neurons and synapses. These results confirm selective and marked degenerations of basal ganglia cholinergic and dopaminergic terminals in PSP. Striatal VAChT reduction may provide a unique neurochemical imaging marker for distinction of PSP from other types of basal ganglia neurodegeneration.

Dopamine D 2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra

Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [ 35S]GTPγS binding) at cloned hD 2 (and hD 3) receptors. At rat striatal membranes, dopamine stimulated [ 35S]GTPγS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D 2/D 3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D 2 receptor antagonist, L741,626. Further, novel antagonists selective for D 3 and D 4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D 2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D 3 and D 4 receptor-selective doses of S33084 and S18126, respectively. In functional ([ 35S]GTPγS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (∼50% stimulation), but significantly greater on the lesioned side (∼80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D 2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D 2, but not D 3 or D 4, receptor-mediated G-protein activation.

Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia.

This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI). The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined. The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation. These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.

Basal ganglia involvement in memory-guided movement sequencing.

The basal ganglia (BG) are thought to play a critical role in motor planning and movement sequencing. While electrophysiological and imaging studies have shown that the dorso-lateral prefrontal cortex (DLPFC) is involved in working memory (WM), the involvement of the BG in this process is not well understood. We used a motor sequencing task to investigate the differential role of BG nuclei in memory-guided movement. Significant activation was observed in the DLPFC and posterior putamen and globus pallidus (GP), with a trend in the caudate and no differences in the anterior putamen. We then investigated the effect of BG outflow on thalamic activation using functional connectivity analysis. Activation in the posterior putamen + GP was found to be correlated with thalamic activation only in the hemisphere contralateral to movement. These results provide the first fMRI evidence that the BG may modulate activity in the thalamus during working memory-guided movement sequencing. Our findings suggest that the BG activation may reflect increased motor sequencing demands during the memory-guided movement condition and, specifically, that the posterior putamen and GP may play a role in maintenance of representations in WM in a manner that contributes to planning and temporal organization of motor sequencing.

Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity in MPTP-treated squirrel monkeys: in vivo and in vitro investigations.

Aromatic L-amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6-[18F]fluoro-L-DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro biochemical determinations of AAAD activity in caudate, putamen, substantia nigra, and nucleus accumbens were performed in the same animals to establish a direct comparison of in vivo and in vitro measurements. In vivo and in vitro AAAD activities in caudate/ putamen were substantially reduced in animals treated with the highest dose of MPTP (2.0 mg/kg). The percent change in the striatal FDOPA uptake (K(i)) and decarboxylation rate constant (k3) values resulting from MPTP treatment showed highly significant correlations with in vitro-determined AAAD activities. However, decarboxylase rates within individual animals presented as approximately 10-fold difference between in vivo and in vitro values. Lower in vivo k3 measurements may be attributed to several possibilities, including transport restrictions limiting substrate availability to AAAD within the neuron. In addition, reductions in AAAD activity in the substantia nigra did not parallel reductions in AAAD activity within the striatum, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously thought.

Dopamine–opioid interactions in the rat striatum: a modulatory role for dopamine D 1 receptors in delta opioid receptor-mediated signal transduction

Dopaminergic and opioidergic systems interact in the striatum to modulate locomotor and motivated behaviors. The present study investigated the molecular interactions of these two systems by determining the role of dopamine D 1 and D 2 receptors in the modulation of opioid receptor-mediated signal transduction. Male Fischer rats were injected daily for 10 days with either saline, the D 1 receptor agonist SKF 82958, the D 2 receptor agonist quinpirole, or both SKF 82958 and quinpirole. Administration of SKF 82958 alone or together with quinpirole attenuated the ability of the delta receptor agonist D-Pen 2,D-Pen 5-enkephalin (DPDPE) to inhibit adenylyl cyclase activity in the caudate putamen and nucleus accumbens. Quinpirole administration alone had no effect. The efficacy and potency of the mu opioid receptor agonist D-Ala 2,N-Me-Phe 4,Gly-ol 5-enkephalin (DAMGO) to inhibit adenylyl cyclase activity was unaltered following administration of either dopamine receptor agonist. Administration of SKF 82958 had no affect on delta receptor binding, forskolin-stimulated adenylyl cyclase activity, or G protein/adenylyl cyclase coupling. However, the ability of DPDPE to stimulate binding of [ 35S]GTPγS to inhibitory G proteins was attenuated in animals that received SKF 82958. These results suggest that repeated activation of D 1 receptors attenuates the functional coupling of delta opioid receptors with adenylyl cyclase due to decreased coupling between delta receptors and G proteins.

Dopaminergic modulation of neuronal activity in the monkey putamen through D1 and D2 receptors during a delayed Go/Nogo task.

Using multibarreled glass micropipettes, we recorded single-unit activity in the putamen, and iontopho retically applied D1 and D2 dopamine receptor agonists (SKF38393, quinpirole) and antagonists (SCH23390, sulpiride) while two monkeys were performing a delayed Go/Nogo task. The putaminal neurons exhibited changes in activity during various task periods (hold, cue, delay, response, and reward periods) in both Go and Nogo trials. Of 296 task-related putaminal neurons, 87 showed activity changes in Go trials only (Go type), 74 in Nogo trials only (Nogo type), 99 in both trials during the same task periods (Both type), and 36 in both trials but during different task periods (Different type). These 296 neurons were examined as regards the effects of both D1 and D2 agonists and/or antagonists, and 234 neurons responded to either D1 - or D2-related substances or both. Among them 41% of neurons responded to the D1 substances only (D1 group), 36% responded to the D2 substances only (D2 group), and 23% responded to both D1 and D2 substances (D1D2 group). During the iontophoretic application of the D1 and D2 substances, most of the responding neurons changed their task-related activity but not their baseline firing rates. The D1 agonist increased the activity in 19 neurons and decreased it in 105 neurons. On the other hand, the D2 agonist increased the activity in 54 neurons and decreased it in 50 neurons. The D1 and D2 substances modulated the activity in both Go and Nogo trials. Each of the three D1/D2 groups (D1, D2, and D1D2 groups) contained all four Go/Nogo types (Go, Nogo, Both, and Different types) of neurons. Percentages of each Go/Nogo type of neuron were comparable among the three D1/D2 groups. The D1 and D2 substances modulated the activity related to various task periods. Each of the three D1/D2 groups included neurons activated during the cue, delay, response, or reward period in Go and Nogo trials. Distributions of the neurons related to each task period were similar among the D1/D2 groups. These results suggest that dopamine can modulate the activity of single putaminal neurons through both D1 and D2 receptors and that the dopaminergic modulation through the two receptors in the putamen affects similar types of signals in behavioral control.

Endothelins promote the activation of astrocytes in rat neostriatum through ET(B) receptors.

The effects of endothelin (ET)-3 and an ET(B) receptor agonist on astrocytic activation in rat caudate putamen were examined by an immunohistochemical staining of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes. A single injection of 40 pmol ET-3 into rat caudate putamen increased the number of GFAP positive cells compared to that in the contralateral saline-injected side. Ala(1,3,11,15)-ET-1 (40 pmol), an ET(B) receptor agonist, also increased the number of striatal GFAP positive cells. The increases in GFAP positive cells were maximum (about 150% of the control side) in 1-2 weeks after injections of the ETs, and then reduced in 4 weeks. A continuous infusion of BQ788, an ET(B) receptor antagonist (23 nmol/day), into the lateral ventricle of the cerebrum antagonized the effect of Ala(1,3,11,15)-ET-1, while BQ788 also reduced the number of GFAP positive cells in saline-injected caudate putamen. Intrastriatal injection of 40 pmol Ala(1,3,11,15)-ET-1 did not affect the number of cells stained by B4 isolectin from Griffonia simplicifolia, which labels activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of Ala(1,3,11,15)-ET-1. These results suggest that activation of ET(B) receptors is involved in the induction of reactive astrocytes.

Analysis of putamen activity related to masticatory sequence in the awake rabbit

Analysis of putamen activity related to masticatory sequence in the awake rabbit

1528 Analysis of putamen activity related to masticatory sequence in the awake rabbit

1528 Analysis of putamen activity related to masticatory sequence in the awake rabbit

Activation of the claustrum in connection with putamen and globus pallidus activity studied by fMRI

Activation of the claustrum in connection with putamen and globus pallidus activity studied by fMRI

Chronic treatment with neuroleptics alters neutral endopeptidase 24.11 activity in rat brain regions

Chronic administration of neuroleptics has been shown to affect the endogenous levels, mRNA, posttranslational processing, and metabolism of neuropeptides in specific regions of rat brain. Neutral endopeptidase 24.11 (NEP) is known to metabolize a variety of neuropeptide substrates, including the enkephalins and neurotensin, thus modifying or terminating the bioactivity of such peptides. In the present study, chronic treatment with haloperidol (1 mg/kg/day, 12 days) increased NEP activity in nucleus accumbens, and chronic treatment with chlorpromazine (4 mg/kg/day, 12 days) increased NEP activity in caudate putamen. Higher dosages with either compound did not significantly alter NEP activity, and none of the treatments altered NEP activity in the hypothalamus. Chronic treatment with apomorphine (5 mg/kg/day, 12 days) decreased NEP activity in both nucleus accumbens and caudate putamen. These data suggest that chronic treatment with neuroleptic drugs may lead to regionally specific alterations in the metabolism of neuropeptides.

<b>DEVELOPMENTAL CHANGES OF PROTEINS ASSOCIATED WITH N-TYPE CALCIUM CHANNELS IN THE RAT </b><b>BRAIN </b>

The basal ganglia and cerebral cortex have close relationship through the striato-pallido-thalamo-cortical loop. The loop circuit is composed of several sub-loops in connection with the modular organization in the basal ganglia, such as the putamino-pallidal and caudate-nigral systems. We sought to reveal functional similarities and differences of these sub-loop systems in the movement mechanisms. Single neuron activity in the primate putamen and caudate nucleus was examined during learned arm movements initiated in 3 different behavioral contexts: Monkeys depressed 3 push buttons laid out in a triangular form on a panel in an instructed sequence using its arm in visually guided, self-initiated and memory-guided modes

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.

Evidence for nuclear ornithine decarboxylase activity in different brain regions of the male rat

The subcellular distribution of ornithine decarboxylating activity in nucleus caudatus putamen, hippocampus, parietal cerebral cortex, cerebellum and hypothalamus of male rat brain has been investigated. The 7000 g supernatant (cytosolic fraction), the 7000 g sediment and the 700 g sediment (nuclear fraction) were incubated with (1 ? (14)C )- labeled ornithine and the (14)CO(2) released was measured. The results demonstrated that 70-75% of the decarboxylating activity was present in the nuclear fraction (700 g sediment), 10% in the 7000 g sediment and 10-20% was found in the cytosol. With more vigorous homogenization (30 strokes instead of 10) an increase in the 7000 g supernatant was obtained. The activity increased linearly with time and amount of tissue added for the 770 g sediment and the 7000 g sediment. A dose-dependent inhibition was found in the whole brain in nuclear and cytosolic fractions with ?-difluoromethylornithine. In all brain areas the nuclear decarboxylating activity was inhibited to 90% with 2.5 mM of ?-difluoromethylornithine except in the hypothalamus, where the inhibition amounted to 20%. An equimolar formation of (14)CO(2) and putrescine was found in the nuclear fraction of all brain regions except the nucleus caudatus putamen and the cerebral cortex, where (14)CO(2) formation exceeded that of putrescine with about 50% suggesting that part of the putrescine is rapidly converted into higher polyamines. It is concluded that with the exception of hypothalamus the major decarboxylating activity in the above mentioned brain regions is ornithine decarboxylase activity (ODC, EC 4.1.1.17) and that the most prominent subcellular localization of this enzyme is the nucleus.

Neuronal activity in monkey ventral putamen in operant learning behaviors

Neuronal activity in monkey ventral putamen in operant learning behaviors

Increased alanine aminotransferase activity in the Huntington's disease putamen

The activities of both mitochondrial and cytosolic forms of alanine aminotransferase are markedly increased in Huntington's disease putamen autopsy samples. This increase was not observed in rats with kainic acid lesions of the striatum, and suggests a considerable alteration of glutamate and pyruvate metabolism as a feature of Huntington's disease.

Reduced GABA transaminase activity in the Huntington's disease putamen

GABA transaminase activity is reduced in autopsied putamen samples from patients dying with Huntington's disease. Its activity is also reduced in the striatum of rats previously lesioned with kainic acid. In both cases, the reduction in GABA transaminase activity is comparable with the reduction in glutamate decarboxylase activity, supporting the suspected localization of this enzyme to GABA neurones within the basal ganglia.