Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP-treated monkeys, and in Parkinson's disease patients

François, Chantal; Savy, Claudine; Jan, Caroline; Tandé, Dominique; Hirsch, Étienne C.; Yelnik, Jérôme

doi:10.1002/1096-9861(20000911)425:1<121::aid-cne10>3.0.co;2-g

Cited by 102 publications

(66 citation statements)

References 29 publications

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“…There are direct projections from STN to the cortex (45, 46) and to the thalamus (47). There are also dopaminergic projections from the SNc to STN (48, 49). Thus, dopamine can be seen to influence all glutamatergic synapses within the basal ganglia–thalamo-cortical circuit (Figure 1).…”

Section: Basal Ganglia Circuitrymentioning

confidence: 99%

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Kishore

Popa

2014

Front. Neurol.

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The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson’s disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during “OFF” and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and “lock” the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information from the environment during motor performance. We propose that in dyskinesias, M1 neurons have lost the ability to depotentiate an activated synapse when exposed to acute pulsatile, non-physiological, dopaminergic surges and become abnormally receptive to unfiltered, aberrant, and non-salient afferent inputs from the environment. The motor program selection in response to such non-salient and behaviorally irrelevant afferent inputs would be abnormal and involuntary. The motor responses are worsened by the lack of normal subcortico–cortical inputs from cerebellum and basal ganglia, because of the aberrant plasticity at their own synapses. Artificial cerebellar stimulation might help re-establish the cerebellar and basal ganglia control over the non-salient inputs to the motor areas during synaptic dopaminergic surges.

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Section: Basal Ganglia Circuitrymentioning

confidence: 99%

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Kishore

Popa

2014

Front. Neurol.

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“…The STN is innervated by dopaminergic axons arising from midbrain dopamine neurons including those in the substantia nigra that are susceptible to degeneration in PD (Hassani et al, 1997; François et al, 2000; Prensa et al, 2000; Cragg et al, 2004). This innervation has, until recently, been overlooked due to its modest nature compared to that found in the striatum.…”

Section: Dopamine In the Stnmentioning

confidence: 99%

Intrinsic dynamics and synaptic inputs control the activity patterns of subthalamic nucleus neurons in health and in Parkinson's disease

Wilson¹,

Bevan²

2011

Neuroscience

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Neurons in the subthalamic nucleus occupy a pivotal position in the circuitry of the basal ganglia. They receive direct excitatory input from the cerebral cortex and the intralaminar nuclei of the thalamus, and directly excite the inhibitory basal ganglia output neurons in the internal segment of the globus pallidus and the substantia nigra. They are also engaged in a reciprocal synaptic arrangement with inhibitory neurons in the external segment of the globus pallidus. Although once viewed as a simple relay of extrinsic input to the basal ganglia, physiological studies of subthalamic neurons have revealed that activity in these neurons does not directly reflect their pattern of extrinsic excitation. Subthalamic neurons are autonomously active at rates comparable to those observed in vivo, and they generate complex patterns of intrinsic activity arising from the interactions between voltage sensitive ion channels on the somatodendritic and axonal membranes. Extrinsic synaptic excitation does not create the firing pattern of the subthalamic neuron, but rather controls the timing of action potentials generated intrinsically. The dopaminergic innervation of the subthalamic nucleus, although moderate, can directly influence firing patterns by acting both on synaptic transmission and voltage-sensitive ion channels responsible for intrinsic properties. Furthermore, chronic dopamine depletion in Parkinson’s disease may modify both synaptic transmission and integration in the subthalamic nucleus, in addition to its effects on other regions of the basal ganglia.

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“…Anatomical studies have demonstrated that the STN receives sparse collaterals from the nigrostriatal pathway which pass the nucleus at its dorsal surface (Lavoie et al, 1989; Hedreen, 1999; Augood et al, 2000; Francois et al, 2000). These inputs form symmetric synapses on dendrites of STN neurons in rats (Cragg et al, 2004) and monkeys (Smith and Kieval, 2000).…”

Section: Extrastriatal Actions Of Dopaminementioning

confidence: 99%

Extrastriatal dopaminergic circuits of the basal ganglia

2010

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The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction.

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Dopaminergic innervation of the subthalamic nucleus in the normal state, in MPTP-treated monkeys, and in Parkinson's disease patients

Cited by 102 publications

References 29 publications

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Intrinsic dynamics and synaptic inputs control the activity patterns of subthalamic nucleus neurons in health and in Parkinson's disease

Extrastriatal dopaminergic circuits of the basal ganglia

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