Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering

L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson's disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link betw...

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Detalles Bibliográficos
Autores: Alcacer, Cristina, Klaus, A., Mendonça, Marcelo da Costa, Abalde, Sara F., Cenci, M.A., Costa, R.M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/403595
Acceso en línea:http://hdl.handle.net/10261/403595
Access Level:acceso abierto
Palabra clave:CP: Neuroscience
IMUs
L-DOPA-induced dyskinesia
behavioral clustering
calcium imaging
freely moving mice
inertial measurement units
motor behavior
parkinson's disease
striatal spiny projection neurons.
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oai_identifier_str oai:digital.csic.es:10261/403595
network_acronym_str ES
network_name_str España
repository_id_str
spelling Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clusteringAlcacer, CristinaKlaus, A.Mendonça, Marcelo da CostaAbalde, Sara F.Cenci, M.A.Costa, R.M.CP: NeuroscienceIMUsL-DOPA-induced dyskinesiabehavioral clusteringcalcium imagingfreely moving miceinertial measurement unitsmotor behaviorparkinson's diseasestriatal spiny projection neurons.L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson's disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link between SPN activity patterns and specific dyskinetic movements remains unknown. To explore this, we implemented a data-driven method for clustering movements based on high-resolution motion sensors and video recordings. In a mouse model of LID, this method identified two main dyskinesia types and pathological rotations, all absent during normal behavior. Using single-cell-resolution imaging, we found that specific sets of both D1- and D2-SPNs were abnormally active during these pathological movements. Under baseline conditions, these SPN sets were active during behaviors sharing physical features with LID movements. These findings indicate that ensembles of behavior-encoding D1- and D2-SPNs form new combinations of hyperactive neurons mediating specific dyskinetic features.Cell PressConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/403595reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)http://dx.doi.org/10.1016/j.celrep.2025.115988Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4035952026-05-22T06:33:51Z
dc.title.none.fl_str_mv Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
title Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
spellingShingle Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
Alcacer, Cristina
CP: Neuroscience
IMUs
L-DOPA-induced dyskinesia
behavioral clustering
calcium imaging
freely moving mice
inertial measurement units
motor behavior
parkinson's disease
striatal spiny projection neurons.
title_short Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
title_full Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
title_fullStr Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
title_full_unstemmed Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
title_sort Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
dc.creator.none.fl_str_mv Alcacer, Cristina
Klaus, A.
Mendonça, Marcelo da Costa
Abalde, Sara F.
Cenci, M.A.
Costa, R.M.
author Alcacer, Cristina
author_facet Alcacer, Cristina
Klaus, A.
Mendonça, Marcelo da Costa
Abalde, Sara F.
Cenci, M.A.
Costa, R.M.
author_role author
author2 Klaus, A.
Mendonça, Marcelo da Costa
Abalde, Sara F.
Cenci, M.A.
Costa, R.M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv CP: Neuroscience
IMUs
L-DOPA-induced dyskinesia
behavioral clustering
calcium imaging
freely moving mice
inertial measurement units
motor behavior
parkinson's disease
striatal spiny projection neurons.
topic CP: Neuroscience
IMUs
L-DOPA-induced dyskinesia
behavioral clustering
calcium imaging
freely moving mice
inertial measurement units
motor behavior
parkinson's disease
striatal spiny projection neurons.
description L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson's disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link between SPN activity patterns and specific dyskinetic movements remains unknown. To explore this, we implemented a data-driven method for clustering movements based on high-resolution motion sensors and video recordings. In a mouse model of LID, this method identified two main dyskinesia types and pathological rotations, all absent during normal behavior. Using single-cell-resolution imaging, we found that specific sets of both D1- and D2-SPNs were abnormally active during these pathological movements. Under baseline conditions, these SPN sets were active during behaviors sharing physical features with LID movements. These findings indicate that ensembles of behavior-encoding D1- and D2-SPNs form new combinations of hyperactive neurons mediating specific dyskinetic features.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/403595
url http://hdl.handle.net/10261/403595
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.celrep.2025.115988
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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