Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%,...

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Autores: Schweizer, Nadine, Pupe, Stéfano, Arvidsson, Emma, Nordenankar, Karin, Smith-Anttila, Casey J. A, Mahmoudi, Souha, Andrén, Anna, Dumas, Sylvie, Rajagopalan, Aparna, Lévesque, Daniel, Leão, Richardson Naves, Wallén-Mackenzie, Åsa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Brasil
Institución:Universidade Federal do Rio Grande do Norte (UFRN)
Repositorio:Repositório Institucional da UFRN
Idioma:inglés
OAI Identifier:oai:repositorio.ufrn.br:1/11818
Acceso en línea:https://repositorio.ufrn.br/jspui/handle/1/11818
Access Level:acceso abierto
Palabra clave:Parkinson disease
deep brain stimulation
vesicular transporter
optogenetics
striatum
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spelling Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotionParkinson diseasedeep brain stimulationvesicular transporteroptogeneticsstriatumThe subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.2014-06-03T13:56:01Z2014-06-03T13:56:01Z2014-04-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfSchweizer, N. et al. Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion. PNAS, 12 apr. 2014.https://repositorio.ufrn.br/jspui/handle/1/11818ark:/41046/001300001487wenginfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNSchweizer, NadinePupe, StéfanoArvidsson, EmmaNordenankar, KarinSmith-Anttila, Casey J. AMahmoudi, SouhaAndrén, AnnaDumas, SylvieRajagopalan, AparnaLévesque, DanielLeão, Richardson NavesWallén-Mackenzie, Åsa2021-07-09T21:20:36Zoai:repositorio.ufrn.br:1/11818Repositório InstitucionalPUBhttp://repositorio.ufrn.br/oai/repositorio@bczm.ufrn.bropendoar:2021-07-09T21:20:36Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.none.fl_str_mv Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
title Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
spellingShingle Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
Schweizer, Nadine
Parkinson disease
deep brain stimulation
vesicular transporter
optogenetics
striatum
title_short Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
title_full Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
title_fullStr Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
title_full_unstemmed Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
title_sort Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
dc.creator.none.fl_str_mv Schweizer, Nadine
Pupe, Stéfano
Arvidsson, Emma
Nordenankar, Karin
Smith-Anttila, Casey J. A
Mahmoudi, Souha
Andrén, Anna
Dumas, Sylvie
Rajagopalan, Aparna
Lévesque, Daniel
Leão, Richardson Naves
Wallén-Mackenzie, Åsa
author Schweizer, Nadine
author_facet Schweizer, Nadine
Pupe, Stéfano
Arvidsson, Emma
Nordenankar, Karin
Smith-Anttila, Casey J. A
Mahmoudi, Souha
Andrén, Anna
Dumas, Sylvie
Rajagopalan, Aparna
Lévesque, Daniel
Leão, Richardson Naves
Wallén-Mackenzie, Åsa
author_role author
author2 Pupe, Stéfano
Arvidsson, Emma
Nordenankar, Karin
Smith-Anttila, Casey J. A
Mahmoudi, Souha
Andrén, Anna
Dumas, Sylvie
Rajagopalan, Aparna
Lévesque, Daniel
Leão, Richardson Naves
Wallén-Mackenzie, Åsa
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.por.fl_str_mv Parkinson disease
deep brain stimulation
vesicular transporter
optogenetics
striatum
topic Parkinson disease
deep brain stimulation
vesicular transporter
optogenetics
striatum
description The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.
publishDate 2014
dc.date.none.fl_str_mv 2014-06-03T13:56:01Z
2014-06-03T13:56:01Z
2014-04-18
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv Schweizer, N. et al. Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion. PNAS, 12 apr. 2014.
https://repositorio.ufrn.br/jspui/handle/1/11818
dc.identifier.dark.fl_str_mv ark:/41046/001300001487w
identifier_str_mv Schweizer, N. et al. Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion. PNAS, 12 apr. 2014.
ark:/41046/001300001487w
url https://repositorio.ufrn.br/jspui/handle/1/11818
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRN
instname:Universidade Federal do Rio Grande do Norte (UFRN)
instacron:UFRN
instname_str Universidade Federal do Rio Grande do Norte (UFRN)
instacron_str UFRN
institution UFRN
reponame_str Repositório Institucional da UFRN
collection Repositório Institucional da UFRN
repository.name.fl_str_mv Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)
repository.mail.fl_str_mv repositorio@bczm.ufrn.br
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score 15.300719

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