Mechanisms for selection of basic motor programs – roles for the striatum and pallidum

Grillner, Sten; Hellgren, Jeanette; Ménard, Ariane; Saitoh, Ken-ichi; Wikström, M.

doi:10.1016/j.tins.2005.05.004

Cited by 526 publications

(412 citation statements)

References 51 publications

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“…We cannot exclude the possibility that RSK2 is also involved, at least partially, in these effects of morphine, but this contribution was undetectable under our experimental conditions. Locomotor responses and sensitization mostly involve neural activity and adaptations within striatal circuits (Grillner et al, 2005), and drug withdrawal engages broad neural networks throughout the brain. Therefore, it is likely that mu opioid receptors do not, or only weakly, recruit RSK2 signaling for these behavioral responses, either because RSK2 is not expressed in recruited neurons or because the mu receptor induces these behavioral responses via other signaling effectors.…”

Section: Discussionmentioning

confidence: 99%

RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

Darcq

Befort

Koebel

et al. 2012

Neuropsychopharmacol

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It has been established that mu opioid receptors activate the ERK1/2 signaling cascade both in vitro and in vivo. The Ser/Thr kinase RSK2 is a direct downstream effector of ERK1/2 and has a role in cellular signaling, cell survival growth, and differentiation; however, its role in biological processes in vivo is less well known. Here we determined whether RSK2 contributes to mu-mediated signaling in vivo. Knockout mice for the rsk2 gene were tested for main morphine effects, including analgesia, tolerance to analgesia, locomotor activation, and sensitization to this effect, as well as morphine withdrawal. The deletion of RSK2 reduced acute morphine analgesia in the tail immersion test, indicating a role for this kinase in mu receptor-mediated nociceptive processing. All other morphine effects and adaptations to chronic morphine were unchanged. Because the mu opioid receptor and RSK2 both show high density in the habenula, we specifically downregulated RSK2 in this brain metastructure using an adeno-associated-virally mediated shRNA approach. Remarkably, morphine analgesia was significantly reduced, as observed in the total knockout animals. Together, these data indicate that RSK2 has a role in nociception, and strongly suggest that a mu opioid receptor-RSK2 signaling mechanism contributes to morphine analgesia at the level of habenula. This study opens novel perspectives for both our understanding of opioid analgesia, and the identification of signaling pathways operating in the habenular complex.

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Section: Discussionmentioning

confidence: 99%

RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

Darcq

Befort

Koebel

et al. 2012

Neuropsychopharmacol

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“…In contrast, no correlation was found for AD. This at first glance incongruous observation could be accounted for by different brain substrates underlying different AIMs, because in contrast to forelimb movements, trunk movements are barely represented in the motor cortex (Donoghue and Wise, 1982;Neafsey et al, 1986), and indeed, it is believed that projections to the brain stem rather than to thalamo-cortical circuits are involved in basal ganglia control of locomotion and posture (Grillner et al, 2005).…”

Section: Severity Of Fd Is Related To Striatal and Motor Cortex Bold mentioning

confidence: 99%

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Delfino

Kalisch

Czisch

et al. 2007

Neuropsychopharmacol

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The mechanisms underlying dopamine agonist-induced dyskinesia in Parkinson's disease remain poorly understood. Similar to patients, rats with severe nigrostriatal degeneration induced by 6-hydroxydopamine are more likely to show dyskinesia during chronic treatment with unselective dopamine receptor agonists than with D2 agonists, suggesting that D1 receptor stimulation alone or in conjunction with D2 receptor stimulation increases the chances of experiencing dyskinesia. As a first step towards disclosing drug-induced brain activation in dyskinesia, we examined the effects of dopamine agonists on behavior and blood oxygenation level-dependent (BOLD) signal in the striatum and motor cortex of rats with unilateral nigrostriatal lesions. Rats were rendered dyskinetic before pharmacologic functional magnetic resonance imaging by means of a repeated treatment regime with dopamine agonists. The unselective agonist apomorphine and the selective D1/D5 agonist SKF-81297 induced strong forelimb dyskinesia (FD) and axial dystonia and increased BOLD signal in the denervated striatum. Besides, SKF-81297 produced a significant but smaller BOLD increase in the intact striatum and a symmetric bilateral increase in the motor cortex. The D2 family agonist quinpirole, which induced mild dyskinesia on chronic treatment, did not produce BOLD changes in the striatum or motor cortex. Further evidence to support an association between BOLD changes and dyskinesia comes from a direct correlation between scores of FD and magnitude of drug-induced BOLD increases in the denervated striatum and motor cortex. Our results suggest that striatal and cortical activation induced by stimulation of D1/D5 receptors has a primary role in the induction of peak dose dyskinesia in parkinsonism.

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“…basal ganglia ͉ brainstem ͉ computational model ͉ lamprey ͉ spinal CPG V ertebrate behavior depends on different sets of neuronal networks specialized to coordinate different motor tasks like locomotion, breathing, and the expression of emotions (1)(2)(3)(4)(5). The activity of these networks is governed by brainstem command centers that are, in turn, under the control of the basal ganglia (1,2).…”

mentioning

confidence: 99%

Simple cellular and network control principles govern complex patterns of motor behavior

Kozlov

Huss²,

Lansner³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The vertebrate central nervous system is organized in modules that independently execute sophisticated tasks. Such modules are flexibly controlled and operate with a considerable degree of autonomy. One example is locomotion generated by spinal central pattern generator networks (CPGs) that shape the detailed motor output. The level of activity is controlled from brainstem locomotor command centers, which in turn, are under the control of the basal ganglia. By using a biophysically detailed, full-scale computational model of the lamprey CPG (10,000 neurons) and its brainstem/forebrain control, we demonstrate general control principles that can adapt the network to different demands. Forward or backward locomotion and steering can be flexibly controlled by local synaptic effects limited to only the very rostral part of the network. Variability in response properties within each neuronal population is an essential feature and assures a constant phase delay along the cord for different locomotor speeds.basal ganglia ͉ brainstem ͉ computational model ͉ lamprey ͉ spinal CPG V ertebrate behavior depends on different sets of neuronal networks specialized to coordinate different motor tasks like locomotion, breathing, and the expression of emotions (1-5). The activity of these networks is governed by brainstem command centers that are, in turn, under the control of the basal ganglia (1, 2). Although the critical role of these networks is well established, their intrinsic mode of operation has, for the most part, remained enigmatic. The lamprey nervous system provides one of the few examples in which detailed knowledge is available, not only of the different types of the participating neurons, but also their membrane properties and synaptic connectivity, particularly with regard to the spinal network (6, 7). Even with this knowledge at hand, it is very difficult, if not impossible, to establish, without the help of modeling, whether the experimental data available are actually sufficient to account for the dynamic operation of the networkand enable exploration of the particular role of different cellular and synaptic components to make predictions of their functional role. To achieve this, we report here a biophysically realistic model of the locomotor network and its control from the brain. The spinal network is composed of excitatory and inhibitory model neurons that, in considerable detail, behave as their biological counterparts. It proved to be important to introduce within each pool of model neurons the known biological variability in neuronal size and membrane properties. Thanks to recent developments in computer technology, we have been able to make a full-scale model of the network with 100 model neurons per segment, each of the Hodgkin-Huxley type-altogether 10,000 neurons connected via 760,000 synapses in the 100 segments. We represent the brainstem command system, as well as the forebrain control from the basal ganglia with an additional 3,500 neurons. Simulations limited to subsamples of neurons have previou...

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Mechanisms for selection of basic motor programs – roles for the striatum and pallidum

Cited by 526 publications

References 51 publications

RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia

Mapping the Effects of Three Dopamine Agonists with Different Dyskinetogenic Potential and Receptor Selectivity Using Pharmacological Functional Magnetic Resonance Imaging

Simple cellular and network control principles govern complex patterns of motor behavior

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