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Striatal Levels (striatal + level)
Selected AbstractsTonically active neurons in the striatum differentiate between delivery and omission of expected reward in a probabilistic task contextEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Paul Apicella Abstract Tonically active neurons (TANs) in the primate striatum are responsive to rewarding stimuli and they are thought to be involved in the storage of stimulus,reward associations or habits. However, it is unclear whether these neurons may signal the difference between the prediction of reward and its actual outcome as a possible neuronal correlate of reward prediction errors at the striatal level. To address this question, we studied the activity of TANs from three monkeys trained in a classical conditioning task in which a liquid reward was preceded by a visual stimulus and reward probability was systematically varied between blocks of trials. The monkeys' ability to discriminate the conditions according to probability was assessed by monitoring their mouth movements during the stimulus,reward interval. We found that the typical TAN pause responses to the delivery of reward were markedly enhanced as the probability of reward decreased, whereas responses to the predictive stimulus were somewhat stronger for high reward probability. In addition, TAN responses to the omission of reward consisted of either decreases or increases in activity that became stronger with increasing reward probability. It therefore appears that one group of neurons differentially responded to reward delivery and reward omission with changes in activity into opposite directions, while another group responded in the same direction. These data indicate that only a subset of TANs could detect the extent to which reward occurs differently than predicted, thus contributing to the encoding of positive and negative reward prediction errors that is relevant to reinforcement learning. [source] Tyrosine hydroxylase-positive neurons intrinsic to the human striatum express the transcription factor Nurr1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Martine Cossette Abstract The putative dopaminergic (DA) neurons intrinsic to human striatum were studied to determine their similarity with DA neurons of the substantia nigra pars compacta (SNpc). The comparison was based on morphological features and on the presence or absence of Nurr1, an orphan receptor of the nuclear receptor family that is essential for the expression of DA phenotype by developing SNpc neurons. Immunohistochemistry for the neuronal nuclear protein (NeuN; a neuronal marker) and in situ hybridization for tyrosine hydroxylase (TH) and/or Nurr1 were applied to post-mortem tissue obtained from seven normal individuals. On one hand, the TH-positive multipolar neurons in the human striatum, which were subdivided into three groups according to their size and pattern of dendritic arborization, were found to be morphologically similar to TH-positive neurons of the SNpc. The distribution frequency of striatal TH-positive neurons, according to their diameter, closely matches the frequency observed for multipolar TH-positive cells in the SNpc. On the other hand, the proportion of neurons expressing Nurr1 and TH mRNA transcripts on single striatal section was similar to the proportion of TH-immunoreactive neurons observed on adjacent sections. More importantly, in each striatum analysed, virtually all cells that stained for TH also expressed NeuN and Nurr1. This study provides novel data that confirm the existence of DA neurons intrinsic to the human striatum. It also provides the first evidence for the existence of striking morphological and chemical similarities between the DA neurons present at striatal level and those that populate the SNpc. [source] Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant eventsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Paul ApicellaArticle first published online: 11 DEC 200 Abstract Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events. [source] Levodopa treatment reverses endocannabinoid system abnormalities in experimental parkinsonismJOURNAL OF NEUROCHEMISTRY, Issue 4 2003Mauro Maccarrone Abstract Cannabinoid receptors and their endogenous ligands are potent inhibitors of neurotransmitter release in the brain. Here, we show that in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of the endocannabinoid anandamide (AEA) were increased, while the activity of its membrane transporter and hydrolase (fatty-acid amide hydrolase, FAAH) were decreased. These changes were not observed in the cerebellum of the same animals. Moreover, the frequency and amplitude of glutamate-mediated spontaneous excitatory post-synaptic currents were augmented in striatal spiny neurones recorded from parkinsonian rats. Remarkably, the anomalies in the endocannabinoid system, as well as those in glutamatergic activity, were completely reversed by chronic treatment of parkinsonian rats with levodopa, and the pharmacological inhibition of FAAH restored a normal glutamatergic activity in 6-OHDA-lesioned animals. Thus, the increased striatal levels of AEA may reflect a compensatory mechanism trying to counteract the abnormal corticostriatal glutamatergic drive in parkinsonian rats. However, this mechanism seems to be unsuccessful, since spontaneous excitatory activity is still higher in these animals. Taken together, these data show that anomalies in the endocannabinoid system induced by experimental parkinsonism are restricted to the striatum and can be reversed by chronic levodopa treatment, and suggest that inhibition of FAAH might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease. [source] Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l -DOPA-induced dyskinesiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003M. Lundblad Abstract We have examined the ability of KW-6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of l -DOPA in 6-hydroxydopamine-lesioned rats. In animals rendered dyskinetic by a previous course of l -DOPA treatment, KW-6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the severity of dyskinesia when coadministered with l -DOPA. A second experiment was undertaken in order to study the effects of KW-6002 in l -DOPA-naive rats. Thirty-five animals were allotted to four groups to receive a 21-day treatment with: (i) KW-6002 (10 mg/kg/day); (ii) l -DOPA (6 mg/kg/day) i.p.; (iii) KW-6002 plus l -DOPA (same doses as above) or (iv) vehicle. Chronic treatment with KW-6002-only produced a significant relief of motor disability in the rotarod test in the absence of any abnormal involuntary movements. Combined treatment with l -DOPA and KW-6002 improved rotarod performance to a significantly higher degree than did each of the two drugs alone. However, this combined treatment induced dyskinesia to about the same degree as did l -DOPA alone. In situ hybridization histochemistry showed that KW-6002 treatment alone caused an approximately 20% reduction in the striatal levels of preproenkephalin mRNA, whereas neither the coadministration of KW-6002 and l -DOPA nor l -DOPA alone significantly altered the expression of this transcript in the dopamine-denervated striatum. Either alone or in combination with l -DOPA, KW-6002 did not have any modulatory effect on prodynorphin mRNA expression or FosB/,FosB-like immunoreactivity in the dopamine-denervated striatum. These results show that monotreatment with an adenosine A2a receptor antagonist can relieve motor disability without inducing behavioural and cellular signs of dyskinesia in rats with 6-hydroxydopamine lesions. Cotreatment with KW-6002 and l -DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug. [source] Critical role of Nitric Oxide on Nicotine-Induced Hyperactivation of Dopaminergic Nigrostriatal System: Electrophysiological and Neurochemical evidence in RatsCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 3 2010Vincenzo Di Matteo Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperactivation elicited by nicotine of the nigrostriatal system was investigated in rats. Nicotine induced a dose-dependent increase of the firing activity of the substantia nigra pars compacta (SNc) DA neurons and DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum. Pharmacological manipulation of the NO system did not produce any change under basal condition in terms of neuronal discharge and DA release. In contrast, pretreatments with two NO synthase (NOS) inhibitors, N-,-nitro- l -arginine methyl ester (l -NAME) and 7-nitroindazole (7-NI) were both capable of blocking the nicotine-induced increase of SNc DA neuron activity and DA striatal levels. The effects of nicotine in l -NAME and 7-NI-pretreated rats were partially restored when rats were pretreated with the NO donor molsidomine. These results further support the evidence of an important role played by NO on modulation of dopaminergic function and drug addiction, thus revealing new pharmacological possibilities in the treatment of nicotine dependence and other DA dysfunctions. [source] | ||||||||||