Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/1/11818 |
Resumo: | 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. |
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Schweizer, NadinePupe, StéfanoArvidsson, EmmaNordenankar, KarinSmith-Anttila, Casey J. AMahmoudi, SouhaAndrén, AnnaDumas, SylvieRajagopalan, AparnaLévesque, DanielLeão, Richardson NavesWallén-Mackenzie, Åsa2014-06-03T13:56:01Z2014-06-03T13:56:01Z2014-04-18Schweizer, 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/1/11818The 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.engParkinson diseasedeep brain stimulationvesicular transporteroptogeneticsstriatumLimiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALRichardsonLeao_ICE_Limiting_2014.pdfRichardsonLeao_ICE_Limiting_2014.pdfapplication/pdf3356815https://repositorio.ufrn.br/bitstream/1/11818/1/RichardsonLeao_ICE_Limiting_2014.pdfca55b5ab2ba3e813d6414885b4ad2555MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81563https://repositorio.ufrn.br/bitstream/1/11818/2/license.txt0d0d8fbe390275e816b5edb78063b7afMD52TEXTRichardsonLeao_ICE_Limiting_2014.pdf.txtRichardsonLeao_ICE_Limiting_2014.pdf.txtExtracted texttext/plain45841https://repositorio.ufrn.br/bitstream/1/11818/7/RichardsonLeao_ICE_Limiting_2014.pdf.txt5d72a3d300009ffcdb52d81b5a2dc205MD57THUMBNAILRichardsonLeao_ICE_Limiting_2014.pdf.jpgRichardsonLeao_ICE_Limiting_2014.pdf.jpgIM Thumbnailimage/jpeg14367https://repositorio.ufrn.br/bitstream/1/11818/8/RichardsonLeao_ICE_Limiting_2014.pdf.jpg6273e12963936978620ce36d1d744517MD581/118182021-07-09 18:20:36.667oai:https://repositorio.ufrn.br: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ório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-07-09T21:20:36Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.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 |
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.contributor.author.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 |
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.accessioned.fl_str_mv |
2014-06-03T13:56:01Z |
dc.date.available.fl_str_mv |
2014-06-03T13:56:01Z |
dc.date.issued.fl_str_mv |
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.citation.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. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/1/11818 |
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. |
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 |
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openAccess |
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