The Basal Ganglia and Disorders of Movement: Pathophysiological Mechanisms

Obeso, José A.; Rodríguez‐Oroz, María C.; Rodrı́guez, Manuel; Arbizu, Javier; Giménez‐Amaya, José Manuel

doi:10.1152/nips.01363.2001

Cited by 71 publications

(106 citation statements)

References 16 publications

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“…The direct pathway, which acts to increase excitatory output from the thalamus to the cortex, contains mainly D 1 dopamine receptors. In contrast, the indirect pathway, which acts to decrease excitatory output from the thalamus to the cortex, contains mainly D 2 dopamine receptors (Obeso, Rodriguez-Oroz, Rodriguez, Arbizu, & Gimenez-Amaya, 2002). Normal motor behavior appears to depend on a balance between the output of the direct and indirect pathways, a balance that both facilitates desired movements and inhibits potentially competing movements.…”

Section: Discussionmentioning

confidence: 99%

Effects of iron deficiency in infancy on patterns of motor development over time

Shafir

Angulo-Barroso

Calatroni

et al. 2006

Human Movement Science

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This longitudinal study of the effects of iron deficiency in infancy assessed motor development over time in 185 healthy Costa Rican children who varied in iron status at 12-23 months. Longitudinal analyses (hierarchical linear modeling) used the Bayley Psychomotor Index before and both 1 week and 3 months after iron treatment in infancy and the Bruninks-Oseretsky Test of Motor Proficiency -long form at 5 years and short form at 11-14 years. Children with chronic severe iron deficiency in infancy had lower motor scores at the beginning of the study and a lower but parallel trajectory for motor scores through early adolescence. Thus, there was no evidence of catch-up in motor development, despite iron therapy in infancy that corrected iron deficiency anemia in all cases.

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Section: Discussionmentioning

confidence: 99%

Effects of iron deficiency in infancy on patterns of motor development over time

Shafir

Angulo-Barroso

Calatroni

et al. 2006

Human Movement Science

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“…The extent of thalamic activity is increased or decreased by proximal components of the basal nuclei, predominantly the medial globus pallidus (mgp) and substantia nigra pars reticulata (snr). 3,15,39,77 These two nuclei utilize GABA and inhibit thalamic nuclei. Therefore, net cortical activity is the product of innate thalamic activity inhibited to varying degrees by the mgp and snr.…”

Section: Basal Motor Tonementioning

confidence: 99%

“…4C) also begins with excitatory, glutaminergic projections from the cerebral cortex to the striatum. 3,15,77 To engage the indirect pathway, striatal neurons that utilize enkephalin and GABA are activated. These project to and inhibit the lgp.…”

Section: 77mentioning

confidence: 99%

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Neuroanatomical Phenotyping in the Mouse: The Dopaminergic System

Zeiss

2005

Vet Pathol

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Abstract. Voluntary movement in animals is modulated by a number of subcortical systems. One of these resides in the basal nuclei and their associated projections and utilizes dopamine as a neurotransmitter. Apart from regulating movement, the dopaminergic axis is also involved in the control of goal-oriented behavior, cognition, and mood. Disorders of this system result in common human neurologic disorders such as Parkinson's and Huntington's diseases, as well contributing to a host of behavioral conditions, such as schizophrenia, attention deficit hyperactivity disorder, and addiction. Many individual mouse models of human dopaminergic dysfunction have been described in varying degrees of detail. However, when evaluating this region of the brain, the veterinary pathologist is confronted by a paucity of information summarizing the comparative aspects of the anatomy, physiology, and pathology of the central dopaminergic system. In this review, a systematic approach to anatomic phenotyping of the central dopaminergic system in the mouse is described and illustrated using tyrosine hydroxylase immunohistochemistry. Differences between murine neuroanatomy and comparable regions of the nonhuman primate brain are highlighted. Although the mouse is the focus of this review, conditions in domestic animals characterized by lesions within the basal nuclei and its projections are also briefly described. Murine behavioral and motor tests that accompany abnormalities of specific anatomic regions of the dopaminergic axis are summarized. Finally, we review mouse models of Parkinson's and Huntington's diseases, as well as those genetically altered mice that elucidate aspects of dopamine metabolism and receptor function.

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“…Slowed movement (bradykinesia) is a prominent symptom of hypodopaminergic states, whether induced acutely with supratherapeutic doses of dopamine-blocking neuroleptic drugs (Fleminger, 1992;Breier et al, 2002) or by chronic lesions of dopamine pathways (Denny-Brown, 1968;Marsden, 1989;Breier et al, 2002;Obeso et al, 2002). Although bradykinesia is ultimately caused by abnormal development of muscle force (Berardelli et al, 2001), the link from dopamine dysfunction to peripheral dynamics remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Bradykinesia Induced by Dopamine D2 Receptor Blockade Is Associated with Reduced Motor Cortex Activity in the Rat

Parr‐Brownlie

Hyland²

2005

Journal of Neuroscience

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Disruption of motor cortex activity is hypothesized to play a major role in the slowed movement (bradykinesia) associated with reduced dopaminergic function. We recorded single neurons in the motor cortex of free-moving rats performing a forelimb-reaching task. The same neurons were examined before and after induction of bradykinesia with the D 2 dopamine receptor antagonist haloperidol. Withincell changes in the firing rate and firing pattern of individual cells and the correlation between simultaneously recorded cells after injection of haloperidol were statistically compared with vehicle-only control experiments. During haloperidol-induced bradykinesia (mean movement time increase, ϩ231%), there was an average 11% decrease in baseline firing rate. Movement-related peaks in firing rate were more dramatically affected, with an overall reduction in peak amplitudes of 40%. Bradykinesia was also associated with decreased intensity of bursting and amplitude of cross-correlation peaks at rest. The results show for the first time that significant reductions can be detected in motor cortex activity at rest in animals with impaired ability to generate movements induced by reduced dopamine action and confirm that impaired movements are associated with reduced cortical activation. Together, these changes in neural activity may reduce recruitment and rate modulation of motor units in the spinal cord.

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The Basal Ganglia and Disorders of Movement: Pathophysiological Mechanisms

Cited by 71 publications

References 16 publications

Effects of iron deficiency in infancy on patterns of motor development over time

Effects of iron deficiency in infancy on patterns of motor development over time

Neuroanatomical Phenotyping in the Mouse: The Dopaminergic System

Bradykinesia Induced by Dopamine D2 Receptor Blockade Is Associated with Reduced Motor Cortex Activity in the Rat

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