Vestibular CCK signaling drives motion sickness-like behavior in mice

We live in an age where travel is paramount. However, one of the most disabling conditions inherent to traveling is motion sickness (MS). While studies have underscored the role of the vestibular system in the development of MS, the neuronal populations involved in motion-induced malaise remain larg...

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Authors: Machuca Márquez, Pablo|||0000-0002-7980-3839, Sánchez Benito, Laura, Menardy, Fabien Louis Joseph|||0000-0002-8712-1344, Urpi, Andrea|||0000-0002-2437-7094, Girona, Mònica, Puighermanal Puigvert, Emma|||0000-0003-4271-9104, Appiah, Isabella|||0000-0002-4684-4992, Palmiter, Richard D.|||0000-0001-6587-0582, Sanz Iglesias, Elisenda|||0000-0002-7932-8556, Quintana Romero, Albert|||0000-0003-1674-7160
Format: article
Publication Date:2023
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:304876
Online Access:https://ddd.uab.cat/record/304876
https://dx.doi.org/urn:doi:10.1073/pnas.2304933120
Access Level:Open access
Keyword:Motion sickness
Vestibular
CCK neurons
Malaise
Optogenetics
id ES_e4505f5c817c171b91ce8fdaae37e60a
oai_identifier_str oai:ddd.uab.cat:304876
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Vestibular CCK signaling drives motion sickness-like behavior in mice
title Vestibular CCK signaling drives motion sickness-like behavior in mice
spellingShingle Vestibular CCK signaling drives motion sickness-like behavior in mice
Machuca Márquez, Pablo|||0000-0002-7980-3839
Motion sickness
Vestibular
CCK neurons
Malaise
Optogenetics
title_short Vestibular CCK signaling drives motion sickness-like behavior in mice
title_full Vestibular CCK signaling drives motion sickness-like behavior in mice
title_fullStr Vestibular CCK signaling drives motion sickness-like behavior in mice
title_full_unstemmed Vestibular CCK signaling drives motion sickness-like behavior in mice
title_sort Vestibular CCK signaling drives motion sickness-like behavior in mice
dc.creator.none.fl_str_mv Machuca Márquez, Pablo|||0000-0002-7980-3839
Sánchez Benito, Laura
Menardy, Fabien Louis Joseph|||0000-0002-8712-1344
Urpi, Andrea|||0000-0002-2437-7094
Girona, Mònica
Puighermanal Puigvert, Emma|||0000-0003-4271-9104
Appiah, Isabella|||0000-0002-4684-4992
Palmiter, Richard D.|||0000-0001-6587-0582
Sanz Iglesias, Elisenda|||0000-0002-7932-8556
Quintana Romero, Albert|||0000-0003-1674-7160
author Machuca Márquez, Pablo|||0000-0002-7980-3839
author_facet Machuca Márquez, Pablo|||0000-0002-7980-3839
Sánchez Benito, Laura
Menardy, Fabien Louis Joseph|||0000-0002-8712-1344
Urpi, Andrea|||0000-0002-2437-7094
Girona, Mònica
Puighermanal Puigvert, Emma|||0000-0003-4271-9104
Appiah, Isabella|||0000-0002-4684-4992
Palmiter, Richard D.|||0000-0001-6587-0582
Sanz Iglesias, Elisenda|||0000-0002-7932-8556
Quintana Romero, Albert|||0000-0003-1674-7160
author_role author
author2 Sánchez Benito, Laura
Menardy, Fabien Louis Joseph|||0000-0002-8712-1344
Urpi, Andrea|||0000-0002-2437-7094
Girona, Mònica
Puighermanal Puigvert, Emma|||0000-0003-4271-9104
Appiah, Isabella|||0000-0002-4684-4992
Palmiter, Richard D.|||0000-0001-6587-0582
Sanz Iglesias, Elisenda|||0000-0002-7932-8556
Quintana Romero, Albert|||0000-0003-1674-7160
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Motion sickness
Vestibular
CCK neurons
Malaise
Optogenetics
topic Motion sickness
Vestibular
CCK neurons
Malaise
Optogenetics
description We live in an age where travel is paramount. However, one of the most disabling conditions inherent to traveling is motion sickness (MS). While studies have underscored the role of the vestibular system in the development of MS, the neuronal populations involved in motion-induced malaise remain largely unknown. Here, we describe the vestibular pathways eliciting MS responses and identify a key role for cholecystokinin (CCK)-expressing vestibular neurons. We reveal that a vestibulo-parabrachial (VN-PBN) CCKergic projection is sufficient to induce conditioned taste avoidance, likely through the activation of calcitonin gene-related peptide-expressing PBN neurons. Finally, we underscore the role of CCK-A receptor signaling as a druggable target to treat MS, providing insight on the neurobiological substrates of MS. Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia, and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activate Calca -expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment.
publishDate 2023
dc.date.none.fl_str_mv 2
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv Article
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VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
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dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/304876
https://dx.doi.org/urn:doi:10.1073/pnas.2304933120
url https://ddd.uab.cat/record/304876
https://dx.doi.org/urn:doi:10.1073/pnas.2304933120
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 658352
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-323
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-720
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RYC-2012-11873
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-125079OA-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-101838-J-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-107633RB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-142544OB-I00
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-57981-P
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-88108-R
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-114977RB-I00
Fundació la Marató de TV3 https://doi.org/10.13039/100008666 202030
"la Caixa" Foundation https://doi.org/10.13039/100010434 LCF/PR/HR20/52400018
"la Caixa" Foundation https://doi.org/10.13039/100010434 100010434
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
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dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
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spelling Vestibular CCK signaling drives motion sickness-like behavior in miceMachuca Márquez, Pablo|||0000-0002-7980-3839Sánchez Benito, LauraMenardy, Fabien Louis Joseph|||0000-0002-8712-1344Urpi, Andrea|||0000-0002-2437-7094Girona, MònicaPuighermanal Puigvert, Emma|||0000-0003-4271-9104Appiah, Isabella|||0000-0002-4684-4992Palmiter, Richard D.|||0000-0001-6587-0582Sanz Iglesias, Elisenda|||0000-0002-7932-8556Quintana Romero, Albert|||0000-0003-1674-7160Motion sicknessVestibularCCK neuronsMalaiseOptogeneticsWe live in an age where travel is paramount. However, one of the most disabling conditions inherent to traveling is motion sickness (MS). While studies have underscored the role of the vestibular system in the development of MS, the neuronal populations involved in motion-induced malaise remain largely unknown. Here, we describe the vestibular pathways eliciting MS responses and identify a key role for cholecystokinin (CCK)-expressing vestibular neurons. We reveal that a vestibulo-parabrachial (VN-PBN) CCKergic projection is sufficient to induce conditioned taste avoidance, likely through the activation of calcitonin gene-related peptide-expressing PBN neurons. Finally, we underscore the role of CCK-A receptor signaling as a druggable target to treat MS, providing insight on the neurobiological substrates of MS. Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia, and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activate Calca -expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/304876https://dx.doi.org/urn:doi:10.1073/pnas.2304933120reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 658352Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-323Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-720Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RYC-2012-11873Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2021-125079OA-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-101838-J-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-107633RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-142544OB-I00Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-57981-PAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2017-88108-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-114977RB-I00Fundació la Marató de TV3 https://doi.org/10.13039/100008666 202030"la Caixa" Foundation https://doi.org/10.13039/100010434 LCF/PR/HR20/52400018"la Caixa" Foundation https://doi.org/10.13039/100010434 100010434open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3048762026-06-06T12:50:31Z
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