Analysis of choreoid hyperkinesia in the rhesus monkey. Surgical and pharmacological analysis of hyperkinesia resulting from lesions in the subthalamic nucleus ol luys

Carpenter, Malcolm B.; Whittier, John R.; Mettler, Fred A.

doi:10.1002/cne.900920303

Cited by 282 publications

(77 citation statements)

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“…The first animal model of a human basal ganglia disorder to be subjected to systematic functional analysis was ballism in the macaque monkey, produced by lesion of the STN (Whittier & Mettler, 1949 ;Carpenter et al 1950). At least 20 % of the nucleus had to be destroyed to induce dyskinesia.…”

Section:    -- mentioning

confidence: 99%

Functional anatomy of movement disorders

Crossman

2000

Journal of Anatomy

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Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and abnormal involuntary movement disorders (dyskinesias) on the other. In Parkinson's disease, degeneration of the nigrostriatal dopamine system leads to overactivity of the ' indirect ' striatopallidal projection to the lateral (external) segment of the globus pallidus. This causes inhibition of lateral pallidal neurons, which in turn project to the subthalamic nucleus. Disinhibition of the subthalamic nucleus leads to abnormal subthalamic overactivity and, as a consequence, overactivity of medial (internal) pallidal output neurons. Dyskinesias, such as are observed in Huntington's disease, levodopa-induced dyskinesia and ballism, share mechanistic features in common and are associated with decreased neuronal activity in both the subthalamic nucleus and the medial globus pallidus.Key words : Basal ganglia ; Parkinson's disease ; akinesia ; dyskinesias.      There are 2 simple and robust conceptual models of movement disorders in basal ganglia disease, one describing the neural mechanisms underlying parkinsonian akinesia and the other explaining the appearance of abnormal involuntary movements (dyskinesias). These represent 2 diametrically opposed mechanisms, at opposite ends of the pathophysiological spectrum. Whilst these models are crude approximations to the complexities of human functional anatomy, nevertheless their validity is borne out by their predictive capacity and practical application in new neurosurgical approaches to the treatment of movement disorders, based on manipulation of the globus pallidus and subthalamic nucleus.The core structures of the basal ganglia are the striatum and globus pallidus (GP), which have close functional associations with the subthalamic nucleus (STN), substantia nigra (SN) and ventral thalamic nuclei. The striatum consists of the caudate nucleus and putamen, which share many similarities of organisation and connections. The putamen is the more overtly motor part of the striatum, receiving connections from the motor areas of the frontal cortex, whilst the caudate nucleus is predominantly connected with more associative cortical regions. The striatum receives the majority of afferent connections to the basal ganglia from extrinsic sources, most notably the dopaminergic nigrostriatal pathway from the pars compacta of the substantia nigra (SNc), a glutamatergic corticostriatal projection and a projection from the intralaminar nuclei of the thalamus. Striatal output neurons, so-called medium spiny neurons, project to 2 main target areas -the globus pallidus and substantia nigra, pars reticulata (SNr). These neurons utilise the inhibitory transmitter, gamma-aminobutyric acid (GABA). The globus pallidus consists of 2 distinct portions, namely the lateral, or external, segment (GPl, GPe) and the medial, or internal, segment (GPm, GPi), both of which receive striatal efferent fibre...

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Section:    -- mentioning

confidence: 99%

Functional anatomy of movement disorders

Crossman

2000

Journal of Anatomy

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“…It receives its main inputs from the cortex, thalamus, and brainstem (Kita, 1994) and, via its glutamatergic projections, excites the GABAergic neurons of the SNr and GPi, thereby reinforcing the inhibitory effects of the BG on the thalamic and brainstem premotor networks (Albin et al, 1989;Alexander and Crutcher, 1990;Chevalier and Deniau, 1990). Pathological or experimental lesions of the STN result in dyskinesia or hemiballism (Whittier and Mettler, 1949;Carpenter et al, 1950;Hammond et al, 1979;Dewey and Jankovic, 1989). STN neurons have higher firing rates and burst activity in Parkinson's disease (PD) patients and animal models of PD than in normal subjects (Miller and DeLong, 1987;Bergman et al, 1994;Hassani et al, 1996;Hutchison et al, 1998;Bevan et al, 2002;Levy et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked to an Increase in Glutamate Levels in the Substantia Nigra Pars Reticulata

Boulet¹,

Lacombe²,

Carcenac³

et al. 2006

J. Neurosci.

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The neurobiological mechanisms by which high-frequency stimulation of the subthalamic nucleus (STN-HFS) alleviates the motor symptoms of Parkinson's disease (PD) remain unclear. In this study, we analyzed the effects of STN-HFS on motor behavior in intact or hemiparkinsonian rats (6-hydroxydopamine lesion of the substantia nigra pars compacta) and investigated the correlation between these effects and extracellular glutamate (Glu) and GABA levels, assessed by intracerebral microdialysis in the substantia nigra pars reticulata (SNr). STN-HFS at an intensity corresponding to the threshold inducing contralateral forelimb dyskinesia, increased Glu levels in the SNr of both intact and hemiparkinsonian rats. In contrast, STN-HFS at half this intensity did not affect Glu levels in the SNr in intact or hemiparkinsonian rats but increased GABA levels in hemiparkinsonian rats only. STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr. These new neurochemical data suggest that STN-HFS-induced forelimb dyskinesia is mediated by glutamate, probably via the direct activation of STN axons, shedding light on the mechanisms of STN-HFS in PD.

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“…1979;Chang et al 2006;Crutcher and DeLong 1984b;Haracz et al 1993;Rolls et al 1983) and STN (Bergman et al 1994;Carpenter et al 1950;Cheruel et al 1996;Georgopoulos 1983;Matsumura et al 1992;Shi et al 2004;Wichmann et al 1994) involvement in normal and pathological movement. However, although striatal involvement in associative and limbic processes has been thoroughly documented (Apicella et al 1991(Apicella et al , 1992(Apicella et al , 1997 Jog et al 1999;Packard and Knowlton 2002;Schultz and Romo 1992;Tremblay et al 1998), it is unclear if the STN plays a parallel role.…”

Section: Introductionmentioning

confidence: 99%

Subthalamic and Striatal Neurons Concurrently Process Motor, Limbic, and Associative Information in Rats Performing an Operant Task

Teagarden

Rebec²

2007

Journal of Neurophysiology

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Teagarden MA, Rebec GV. Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task. J Neurophysiol 97: [2042][2043][2044][2045][2046][2047][2048][2049][2050][2051][2052][2053][2054][2055][2056][2057][2058] 2007. First published December 20, 2006; doi:10.1152/jn.00368.2006. Although the subthalamic nucleus (STN) is commonly assumed to be a relay for striatal (STR) output, anatomical evidence suggests the two structures are connected in parallel, raising the possibility that parallel STN and STR firing patterns mediate behavioral processes. The STR is known to play a role in associative and limbic processes, and although behavioral studies suggest that the STN may do so as well, evaluation of this hypothesis is complicated by a lack of pertinent STN physiological data. We recorded concurrent STN and STR firing patterns in rats learning an operant nose-poke task. Both structures responded in similar proportions to task events including instructive cues, discriminative nose-pokes, and sucrose reinforcement. Neuronal responses to reinforcement comprised phasic excitations preceding reinforcement and inhibitions afterward; the inhibition was attenuated when reinforcement was absent. Reinforcement responses occurred more frequently during later training sessions in which discriminative action was required, suggesting that responses were context-dependent. Nose-pokes were typically preceded by excitations; there also was a nonsignificant trend toward inhibition encoding correct nosepokes. Sustained changes in firing rate coinciding with specific task events suggested that both nuclei were encoding behavioral sequences; this is the first report of such behavior in the STN. Our findings also reveal complex STN responses to reinforcement. Thus both STN and STR neurons show concurrent involvement in motor, limbic, and associative processes. I N T R O D U C T I O NInterpretation of theoretical and empirical research within the basal ganglia is colored, if not constrained, by the notion of an architecture in which the striatum (STR) receives cortical and thalamic input and routes its output to the substantia nigra along two pathways, one of which comprises the globus pallidus and subthalamic nucleus (STN) (Albin et al. 1989;DeLong 1990). In this view, these nuclei had no extra-basal ganglia inputs of their own, and so they were considered relays for striatal firing patterns. However, there is considerable evidence that the STN receives direct cortical (Hartmann-von Monakow et al. 1978;Nambu et al. 1996), thalamic (Sugimoto et al. 1983), and midbrain input. Because the STN and STR receive direct input from the same cortical and midbrain regions, the STN is in a position to act as a second, independent input area of the basal ganglia. Both of these nuclei project directly to the output areas of the basal ganglia (the substantia nigra pars reticulata and internal globus pallidus), and both are reciprocally connected with the external globus pallidus. Thus ...

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Analysis of choreoid hyperkinesia in the rhesus monkey. Surgical and pharmacological analysis of hyperkinesia resulting from lesions in the subthalamic nucleus ol luys

Cited by 282 publications

References 9 publications

Functional anatomy of movement disorders

Functional anatomy of movement disorders

Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked to an Increase in Glutamate Levels in the Substantia Nigra Pars Reticulata

Subthalamic and Striatal Neurons Concurrently Process Motor, Limbic, and Associative Information in Rats Performing an Operant Task

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