Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients
Identifieur interne : 000B95 ( Main/Exploration ); précédent : 000B94; suivant : 000B96Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients
Auteurs : I. A. Prescott [Canada] ; J. O. Dostrovsky [Canada] ; E. Moro [Canada] ; M. Hodaie [Canada] ; A. M. Lozano [Canada] ; W. D. Hutchison [Canada]Source :
- Brain [ 0006-8950 ] ; 2009-02.
Abstract
Parkinson's disease, caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (l-dopa) is the most effective treatment for the amelioration of Parkinson's disease signs and symptoms, but long-term administration can lead to disabling motor fluctuations and l-dopa -induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 Parkinson's disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS—four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral l-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity-dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.
Url:
DOI: 10.1093/brain/awn322
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients</title><author><name sortKey="Prescott, I A" sort="Prescott, I A" uniqKey="Prescott I" first="I. A." last="Prescott">I. A. Prescott</name></author><author><name sortKey="Dostrovsky, J O" sort="Dostrovsky, J O" uniqKey="Dostrovsky J" first="J. O." last="Dostrovsky">J. O. Dostrovsky</name></author><author><name sortKey="Moro, E" sort="Moro, E" uniqKey="Moro E" first="E." last="Moro">E. Moro</name></author><author><name sortKey="Hodaie, M" sort="Hodaie, M" uniqKey="Hodaie M" first="M." last="Hodaie">M. Hodaie</name></author><author><name sortKey="Lozano, A M" sort="Lozano, A M" uniqKey="Lozano A" first="A. M." last="Lozano">A. M. Lozano</name></author><author><name sortKey="Hutchison, W D" sort="Hutchison, W D" uniqKey="Hutchison W" first="W. D." last="Hutchison">W. D. Hutchison</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4324554E8404D80ADB0824159A9CBCF287E45680</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1093/brain/awn322</idno><idno type="url">https://api.istex.fr/document/4324554E8404D80ADB0824159A9CBCF287E45680/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">003015</idno><idno type="wicri:Area/Main/Curation">002C24</idno><idno type="wicri:Area/Main/Exploration">000B95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients</title><author><name sortKey="Prescott, I A" sort="Prescott, I A" uniqKey="Prescott I" first="I. A." last="Prescott">I. A. Prescott</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Dostrovsky, J O" sort="Dostrovsky, J O" uniqKey="Dostrovsky J" first="J. O." last="Dostrovsky">J. O. Dostrovsky</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Moro, E" sort="Moro, E" uniqKey="Moro E" first="E." last="Moro">E. Moro</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hodaie, M" sort="Hodaie, M" uniqKey="Hodaie M" first="M." last="Hodaie">M. Hodaie</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lozano, A M" sort="Lozano, A M" uniqKey="Lozano A" first="A. M." last="Lozano">A. M. Lozano</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hutchison, W D" sort="Hutchison, W D" uniqKey="Hutchison W" first="W. D." last="Hutchison">W. D. Hutchison</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>1 Department of Physiology, University of Toronto, Canada 2 Division of Neurosurgery, Department of Surgery, Toronto Western Research Institute and Krembil Neuroscience Centre</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Canada</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-02">2009-02</date><biblScope unit="volume">132</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="309">309</biblScope><biblScope unit="page" to="318">318</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">4324554E8404D80ADB0824159A9CBCF287E45680</idno><idno type="DOI">10.1093/brain/awn322</idno><idno type="ArticleID">awn322</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Parkinson's disease, caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (l-dopa) is the most effective treatment for the amelioration of Parkinson's disease signs and symptoms, but long-term administration can lead to disabling motor fluctuations and l-dopa -induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 Parkinson's disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS—four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral l-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity-dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Prescott, I A" sort="Prescott, I A" uniqKey="Prescott I" first="I. A." last="Prescott">I. A. Prescott</name></region><name sortKey="Dostrovsky, J O" sort="Dostrovsky, J O" uniqKey="Dostrovsky J" first="J. O." last="Dostrovsky">J. O. Dostrovsky</name><name sortKey="Hodaie, M" sort="Hodaie, M" uniqKey="Hodaie M" first="M." last="Hodaie">M. Hodaie</name><name sortKey="Hutchison, W D" sort="Hutchison, W D" uniqKey="Hutchison W" first="W. D." last="Hutchison">W. D. Hutchison</name><name sortKey="Hutchison, W D" sort="Hutchison, W D" uniqKey="Hutchison W" first="W. D." last="Hutchison">W. D. Hutchison</name><name sortKey="Lozano, A M" sort="Lozano, A M" uniqKey="Lozano A" first="A. M." last="Lozano">A. M. Lozano</name><name sortKey="Moro, E" sort="Moro, E" uniqKey="Moro E" first="E." last="Moro">E. Moro</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B95 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000B95 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:4324554E8404D80ADB0824159A9CBCF287E45680
|texte= Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients
}}
| This area was generated with Dilib version V0.6.23. |  |