Macrophages excite muscle spindles with glutamate to bolster locomotion

Autores
Yan, Yuyang; Antolin, Nuria; Zhou, Luming; Xu, Luyang; Vargas, Irene Lisa; Gomez Martinez, Carlos Daniel; Kong, Guiping; Palmisano, Ilaria; Yang, Yi; Chadwick, Jessica; Müller, Franziska; Bull, Anthony M. J.; Lo Celso, Cristina; Primiano, Guido; Servidei, Serenella; Perrier, Jean François; Bellardita, Carmelo; Di Giovanni, Simone
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.
Fil: Yan, Yuyang. Imperial College. London Institute Of Medical Sciences.;
Fil: Antolin, Nuria. Universidad de Copenhagen; Dinamarca
Fil: Zhou, Luming. Imperial College. London Institute Of Medical Sciences.;
Fil: Xu, Luyang. Imperial College. London Institute Of Medical Sciences.;
Fil: Vargas, Irene Lisa. Universidad de Copenhagen; Dinamarca
Fil: Gomez Martinez, Carlos Daniel. Universidad de Copenhagen; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Kong, Guiping. Imperial College. London Institute Of Medical Sciences.;
Fil: Palmisano, Ilaria. Imperial College. London Institute Of Medical Sciences.;
Fil: Yang, Yi. Imperial College. London Institute Of Medical Sciences.;
Fil: Chadwick, Jessica. Imperial College. London Institute Of Medical Sciences.;
Fil: Müller, Franziska. Imperial College. London Institute Of Medical Sciences.;
Fil: Bull, Anthony M. J.. Imperial College. London Institute Of Medical Sciences.;
Fil: Lo Celso, Cristina. Imperial College. London Institute Of Medical Sciences.;
Fil: Primiano, Guido. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; Italia
Fil: Servidei, Serenella. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; Italia
Fil: Perrier, Jean François. Universidad de Copenhagen; Dinamarca
Fil: Bellardita, Carmelo. Universidad de Copenhagen; Dinamarca
Fil: Di Giovanni, Simone. Imperial College. London Institute Of Medical Sciences.;
Materia
Motoneurons
Glutamate
Electrophysiology
Muscle-spindles
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266925
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Macrophages excite muscle spindles with glutamate to bolster locomotionYan, YuyangAntolin, NuriaZhou, LumingXu, LuyangVargas, Irene LisaGomez Martinez, Carlos DanielKong, GuipingPalmisano, IlariaYang, YiChadwick, JessicaMüller, FranziskaBull, Anthony M. J.Lo Celso, CristinaPrimiano, GuidoServidei, SerenellaPerrier, Jean FrançoisBellardita, CarmeloDi Giovanni, SimoneMotoneuronsGlutamateElectrophysiologyMuscle-spindleshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.Fil: Yan, Yuyang. Imperial College. London Institute Of Medical Sciences.;Fil: Antolin, Nuria. Universidad de Copenhagen; DinamarcaFil: Zhou, Luming. Imperial College. London Institute Of Medical Sciences.;Fil: Xu, Luyang. Imperial College. London Institute Of Medical Sciences.;Fil: Vargas, Irene Lisa. Universidad de Copenhagen; DinamarcaFil: Gomez Martinez, Carlos Daniel. Universidad de Copenhagen; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Kong, Guiping. Imperial College. London Institute Of Medical Sciences.;Fil: Palmisano, Ilaria. Imperial College. London Institute Of Medical Sciences.;Fil: Yang, Yi. Imperial College. London Institute Of Medical Sciences.;Fil: Chadwick, Jessica. Imperial College. London Institute Of Medical Sciences.;Fil: Müller, Franziska. Imperial College. London Institute Of Medical Sciences.;Fil: Bull, Anthony M. J.. Imperial College. London Institute Of Medical Sciences.;Fil: Lo Celso, Cristina. Imperial College. London Institute Of Medical Sciences.;Fil: Primiano, Guido. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; ItaliaFil: Servidei, Serenella. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; ItaliaFil: Perrier, Jean François. Universidad de Copenhagen; DinamarcaFil: Bellardita, Carmelo. Universidad de Copenhagen; DinamarcaFil: Di Giovanni, Simone. Imperial College. London Institute Of Medical Sciences.;Nature Publishing Group2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266925Yan, Yuyang; Antolin, Nuria; Zhou, Luming; Xu, Luyang; Vargas, Irene Lisa; et al.; Macrophages excite muscle spindles with glutamate to bolster locomotion; Nature Publishing Group; Nature; 637; 8046; 12-2024; 698-7070028-0836CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41586-024-08272-5info:eu-repo/semantics/altIdentifier/doi/10.1038/s41586-024-08272-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:32Zoai:ri.conicet.gov.ar:11336/266925instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:32.652CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Macrophages excite muscle spindles with glutamate to bolster locomotion
title Macrophages excite muscle spindles with glutamate to bolster locomotion
spellingShingle Macrophages excite muscle spindles with glutamate to bolster locomotion
Yan, Yuyang
Motoneurons
Glutamate
Electrophysiology
Muscle-spindles
title_short Macrophages excite muscle spindles with glutamate to bolster locomotion
title_full Macrophages excite muscle spindles with glutamate to bolster locomotion
title_fullStr Macrophages excite muscle spindles with glutamate to bolster locomotion
title_full_unstemmed Macrophages excite muscle spindles with glutamate to bolster locomotion
title_sort Macrophages excite muscle spindles with glutamate to bolster locomotion
dc.creator.none.fl_str_mv Yan, Yuyang
Antolin, Nuria
Zhou, Luming
Xu, Luyang
Vargas, Irene Lisa
Gomez Martinez, Carlos Daniel
Kong, Guiping
Palmisano, Ilaria
Yang, Yi
Chadwick, Jessica
Müller, Franziska
Bull, Anthony M. J.
Lo Celso, Cristina
Primiano, Guido
Servidei, Serenella
Perrier, Jean François
Bellardita, Carmelo
Di Giovanni, Simone
author Yan, Yuyang
author_facet Yan, Yuyang
Antolin, Nuria
Zhou, Luming
Xu, Luyang
Vargas, Irene Lisa
Gomez Martinez, Carlos Daniel
Kong, Guiping
Palmisano, Ilaria
Yang, Yi
Chadwick, Jessica
Müller, Franziska
Bull, Anthony M. J.
Lo Celso, Cristina
Primiano, Guido
Servidei, Serenella
Perrier, Jean François
Bellardita, Carmelo
Di Giovanni, Simone
author_role author
author2 Antolin, Nuria
Zhou, Luming
Xu, Luyang
Vargas, Irene Lisa
Gomez Martinez, Carlos Daniel
Kong, Guiping
Palmisano, Ilaria
Yang, Yi
Chadwick, Jessica
Müller, Franziska
Bull, Anthony M. J.
Lo Celso, Cristina
Primiano, Guido
Servidei, Serenella
Perrier, Jean François
Bellardita, Carmelo
Di Giovanni, Simone
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Motoneurons
Glutamate
Electrophysiology
Muscle-spindles
topic Motoneurons
Glutamate
Electrophysiology
Muscle-spindles
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.
Fil: Yan, Yuyang. Imperial College. London Institute Of Medical Sciences.;
Fil: Antolin, Nuria. Universidad de Copenhagen; Dinamarca
Fil: Zhou, Luming. Imperial College. London Institute Of Medical Sciences.;
Fil: Xu, Luyang. Imperial College. London Institute Of Medical Sciences.;
Fil: Vargas, Irene Lisa. Universidad de Copenhagen; Dinamarca
Fil: Gomez Martinez, Carlos Daniel. Universidad de Copenhagen; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Kong, Guiping. Imperial College. London Institute Of Medical Sciences.;
Fil: Palmisano, Ilaria. Imperial College. London Institute Of Medical Sciences.;
Fil: Yang, Yi. Imperial College. London Institute Of Medical Sciences.;
Fil: Chadwick, Jessica. Imperial College. London Institute Of Medical Sciences.;
Fil: Müller, Franziska. Imperial College. London Institute Of Medical Sciences.;
Fil: Bull, Anthony M. J.. Imperial College. London Institute Of Medical Sciences.;
Fil: Lo Celso, Cristina. Imperial College. London Institute Of Medical Sciences.;
Fil: Primiano, Guido. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; Italia
Fil: Servidei, Serenella. Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Italia. Università Cattolica del Sacro Cuore; Italia
Fil: Perrier, Jean François. Universidad de Copenhagen; Dinamarca
Fil: Bellardita, Carmelo. Universidad de Copenhagen; Dinamarca
Fil: Di Giovanni, Simone. Imperial College. London Institute Of Medical Sciences.;
description The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266925
Yan, Yuyang; Antolin, Nuria; Zhou, Luming; Xu, Luyang; Vargas, Irene Lisa; et al.; Macrophages excite muscle spindles with glutamate to bolster locomotion; Nature Publishing Group; Nature; 637; 8046; 12-2024; 698-707
0028-0836
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266925
identifier_str_mv Yan, Yuyang; Antolin, Nuria; Zhou, Luming; Xu, Luyang; Vargas, Irene Lisa; et al.; Macrophages excite muscle spindles with glutamate to bolster locomotion; Nature Publishing Group; Nature; 637; 8046; 12-2024; 698-707
0028-0836
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41586-024-08272-5
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41586-024-08272-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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