Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning

Despite evidence that dopamine neurotransmission in the striatum is critical for learning as well as for movement control, little is yet known about how the learning-related dynamics of striatal activity are affected by dopamine depletion, a condition faced in Parkinson's disease. We made local...

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Autores: F. Hernandez, Ledia, Kubota, Yasuo, Hu, Dan, Howe, Mark W, Lemaire, Nune, Graybiel, Ann M
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1228
Acceso en línea:https://www.jneurosci.org/content/33/11/4782
http://hdl.handle.net/20.500.12020/1228
https://doi.org/10.1523/JNEUROSCI.3746-12.2013
Access Level:acceso abierto
Palabra clave:Biología Celular y Molecular
Ciencias Biomédicas
Dopamine
Parkinson’s disease
Striatum
24 Ciencias de la Vida
2490 Neurociencias
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oai_identifier_str oai:repositorio.ucjc.edu:20.500.12020/1228
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spelling Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learningF. Hernandez, LediaKubota, YasuoHu, DanHowe, Mark WLemaire, NuneGraybiel, Ann MBiología Celular y MolecularCiencias BiomédicasDopamineParkinson’s diseaseStriatum24 Ciencias de la Vida2490 NeurocienciasDespite evidence that dopamine neurotransmission in the striatum is critical for learning as well as for movement control, little is yet known about how the learning-related dynamics of striatal activity are affected by dopamine depletion, a condition faced in Parkinson's disease. We made localized intrastriatal 6-hydroxydopamine lesions in rats and recorded within the dopamine-depleted sensorimotor striatal zone and its contralateral correspondent as the animals learned a conditional maze task. Rather than producing global, nonspecific elevations in firing rate across the task, the dopamine depletion altered striatal projection neuron activity and fast-spiking interneuron activity selectively, with sharply task-specific and cell type-specific effects, and often, with learning-stage selective effects as well. Striatal projection neurons with strong responses during the maze runs had especially elevated responsiveness during the maze runs. Projection neurons that, instead, fired most strongly before maze running showed elevated pre-start firing rates, but not during maze running, as learning progressed. The intrastriatal dopamine depletion severely affected the learning-related patterning of fast-spiking interneuron ensembles, especially during maze running and after extended training. Remarkably, L-DOPA treatment almost entirely reversed the depletion-induced elevations in pre-run firing of the projection neurons, and elevated their responses around start and end of maze runs. By contrast, L-DOPA failed to normalize fast-spiking interneuron activity. Thus the effects of striatal dopamine depletion and restoration on striatal activity are highly dependent not only on cell type, as previously shown, but also on the behavioral activity called for and the state of behavioral learning achieved.This work was funded by National Institutes of Health–National Institute of Neurological Disorders and Stroke P50 NS-38372, National Parkinson Foundation and Stanley H. and Sheila G. Sydney Fund to A.M.G., and Parkinson Disease Foundation Fellowship and Fulbright Fellowship to L.F.H.Society for Neuroscience2013info:eu-repo/semantics/articlehttps://www.jneurosci.org/content/33/11/4782https://www.jneurosci.org/content/33/11/4782http://hdl.handle.net/20.500.12020/1228https://doi.org/10.1523/JNEUROSCI.3746-12.2013reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)InglésNational Institutes of Health–National Institute of Neurological Disorders and Stroke P50 NS-38372info:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/12282026-05-27T07:36:51Z
dc.title.none.fl_str_mv Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
title Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
spellingShingle Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
F. Hernandez, Ledia
Biología Celular y Molecular
Ciencias Biomédicas
Dopamine
Parkinson’s disease
Striatum
24 Ciencias de la Vida
2490 Neurociencias
title_short Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
title_full Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
title_fullStr Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
title_full_unstemmed Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
title_sort Selective effects of dopamine depletion on neuronal subpopulations in the sensorimotor striatum during procedural learning
dc.creator.none.fl_str_mv F. Hernandez, Ledia
Kubota, Yasuo
Hu, Dan
Howe, Mark W
Lemaire, Nune
Graybiel, Ann M
author F. Hernandez, Ledia
author_facet F. Hernandez, Ledia
Kubota, Yasuo
Hu, Dan
Howe, Mark W
Lemaire, Nune
Graybiel, Ann M
author_role author
author2 Kubota, Yasuo
Hu, Dan
Howe, Mark W
Lemaire, Nune
Graybiel, Ann M
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Biología Celular y Molecular
Ciencias Biomédicas
Dopamine
Parkinson’s disease
Striatum
24 Ciencias de la Vida
2490 Neurociencias
topic Biología Celular y Molecular
Ciencias Biomédicas
Dopamine
Parkinson’s disease
Striatum
24 Ciencias de la Vida
2490 Neurociencias
description Despite evidence that dopamine neurotransmission in the striatum is critical for learning as well as for movement control, little is yet known about how the learning-related dynamics of striatal activity are affected by dopamine depletion, a condition faced in Parkinson's disease. We made localized intrastriatal 6-hydroxydopamine lesions in rats and recorded within the dopamine-depleted sensorimotor striatal zone and its contralateral correspondent as the animals learned a conditional maze task. Rather than producing global, nonspecific elevations in firing rate across the task, the dopamine depletion altered striatal projection neuron activity and fast-spiking interneuron activity selectively, with sharply task-specific and cell type-specific effects, and often, with learning-stage selective effects as well. Striatal projection neurons with strong responses during the maze runs had especially elevated responsiveness during the maze runs. Projection neurons that, instead, fired most strongly before maze running showed elevated pre-start firing rates, but not during maze running, as learning progressed. The intrastriatal dopamine depletion severely affected the learning-related patterning of fast-spiking interneuron ensembles, especially during maze running and after extended training. Remarkably, L-DOPA treatment almost entirely reversed the depletion-induced elevations in pre-run firing of the projection neurons, and elevated their responses around start and end of maze runs. By contrast, L-DOPA failed to normalize fast-spiking interneuron activity. Thus the effects of striatal dopamine depletion and restoration on striatal activity are highly dependent not only on cell type, as previously shown, but also on the behavioral activity called for and the state of behavioral learning achieved.
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.jneurosci.org/content/33/11/4782
https://www.jneurosci.org/content/33/11/4782
http://hdl.handle.net/20.500.12020/1228
https://doi.org/10.1523/JNEUROSCI.3746-12.2013
url https://www.jneurosci.org/content/33/11/4782
http://hdl.handle.net/20.500.12020/1228
https://doi.org/10.1523/JNEUROSCI.3746-12.2013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv National Institutes of Health–National Institute of Neurological Disorders and Stroke P50 NS-38372
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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