Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.

After spinal cord injury (SCI), cyclic adenosine monophosphate (cAMP) levels drop in the spinal cord, cortex and brainstem, unlike in regenerating peripheral neurons. To address SCI recovery, we expressed photoactivatable adenylate cyclase (bPAC) in corticospinal neurons of female rats with dorsal h...

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Autores: Martínez-Rojas B, Martín-Pérez S, Giraldo E, Lopez-Mocholi E, Alastrue A, Andrade-Talavera Y, Prius-Mengual J, Paniagua G, Pedraza M, Hingorani S, Rost BR, Schmitz D, Llansola M, Felipo V, Rodríguez-Moreno A, Moreno-Manzano V
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Centro de Investigación Principe Felipe (CIPF)
Repositorio:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p4573
Acceso en línea:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4573
Access Level:acceso abierto
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spelling Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.Martínez-Rojas BMartín-Pérez SGiraldo ELopez-Mocholi EAlastrue AAndrade-Talavera YPrius-Mengual JPaniagua GPedraza MHingorani SRost BRSchmitz DLlansola MFelipo VRodríguez-Moreno AMoreno-Manzano VAfter spinal cord injury (SCI), cyclic adenosine monophosphate (cAMP) levels drop in the spinal cord, cortex and brainstem, unlike in regenerating peripheral neurons. To address SCI recovery, we expressed photoactivatable adenylate cyclase (bPAC) in corticospinal neurons of female rats with dorsal hemisection for on-demand cAMP inductions. bPAC stimulation restored passive and firing properties of corticospinal neurons, promoted early and sustained locomotor recovery and increased corticospinal tract plasticity. Additionally, bPAC enhanced sparing of lumbar-projecting brainstem neurons after SCI, accompanied by activation of cAMP signaling in the raphe-reticular formation and increased excitatory/inhibitory neurotransmitter balance. Accordingly, augmented density of serotonergic tracts was found caudal to the injury in bPAC rats, correlating with enhanced functional performance. Serotonergic implication in motor recovery was further evidenced by selective depletion, resulting in the abrogation of bPAC-mediated recovery. Overall, our findings underscore that cAMP induction in corticospinal neurons enhances locomotion after SCI, through a cortical rerouting pathway via the serotonergic descending tract.NATURE PORTFOLIO2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4573Nature CommunicationsISSN: 20411723reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)instname:Centro de Investigación Principe Felipe (CIPF)Inglésinfo:eu-repo/semantics/openAccessoai:cipf.fundanetsuite.com:p45732026-06-17T11:19:47Z
dc.title.none.fl_str_mv Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
title Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
spellingShingle Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
Martínez-Rojas B
title_short Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
title_full Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
title_fullStr Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
title_full_unstemmed Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
title_sort Stimulation of corticospinal neurons by optogenetic cAMP inductions promotes motor recovery after spinal cord injury in female rats via raphespinal tract modulation.
dc.creator.none.fl_str_mv Martínez-Rojas B
Martín-Pérez S
Giraldo E
Lopez-Mocholi E
Alastrue A
Andrade-Talavera Y
Prius-Mengual J
Paniagua G
Pedraza M
Hingorani S
Rost BR
Schmitz D
Llansola M
Felipo V
Rodríguez-Moreno A
Moreno-Manzano V
author Martínez-Rojas B
author_facet Martínez-Rojas B
Martín-Pérez S
Giraldo E
Lopez-Mocholi E
Alastrue A
Andrade-Talavera Y
Prius-Mengual J
Paniagua G
Pedraza M
Hingorani S
Rost BR
Schmitz D
Llansola M
Felipo V
Rodríguez-Moreno A
Moreno-Manzano V
author_role author
author2 Martín-Pérez S
Giraldo E
Lopez-Mocholi E
Alastrue A
Andrade-Talavera Y
Prius-Mengual J
Paniagua G
Pedraza M
Hingorani S
Rost BR
Schmitz D
Llansola M
Felipo V
Rodríguez-Moreno A
Moreno-Manzano V
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description After spinal cord injury (SCI), cyclic adenosine monophosphate (cAMP) levels drop in the spinal cord, cortex and brainstem, unlike in regenerating peripheral neurons. To address SCI recovery, we expressed photoactivatable adenylate cyclase (bPAC) in corticospinal neurons of female rats with dorsal hemisection for on-demand cAMP inductions. bPAC stimulation restored passive and firing properties of corticospinal neurons, promoted early and sustained locomotor recovery and increased corticospinal tract plasticity. Additionally, bPAC enhanced sparing of lumbar-projecting brainstem neurons after SCI, accompanied by activation of cAMP signaling in the raphe-reticular formation and increased excitatory/inhibitory neurotransmitter balance. Accordingly, augmented density of serotonergic tracts was found caudal to the injury in bPAC rats, correlating with enhanced functional performance. Serotonergic implication in motor recovery was further evidenced by selective depletion, resulting in the abrogation of bPAC-mediated recovery. Overall, our findings underscore that cAMP induction in corticospinal neurons enhances locomotion after SCI, through a cortical rerouting pathway via the serotonergic descending tract.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4573
url https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4573
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv NATURE PORTFOLIO
publisher.none.fl_str_mv NATURE PORTFOLIO
dc.source.none.fl_str_mv Nature Communications
ISSN: 20411723
reponame:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
instname:Centro de Investigación Principe Felipe (CIPF)
instname_str Centro de Investigación Principe Felipe (CIPF)
reponame_str r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
collection r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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