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| Pàgina inicial > Articles > Articles publicats > Vestibular CCK signaling drives motion sickness-like behavior in mice |
(Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències) (Universitat Autònoma de Barcelona. Institut de Neurociències) (University of Washington) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (North-West University (Potchefstroom, Sud-àfrica))
| Data: | 2023 |
| Resum: | 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. |
| Ajuts: | European Commission 658352 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-323 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-720 Ministerio de Economía y Competitividad RYC-2012-11873 Agencia Estatal de Investigación PID2021-125079OA-I00 Agencia Estatal de Investigación RTI2018-101838-J-I00 Agencia Estatal de Investigación PID2019-107633RB-I00 Agencia Estatal de Investigación PID2022-142544OB-I00 Ministerio de Economía y Competitividad SAF2014-57981-P Agencia Estatal de Investigación SAF2017-88108-R Agencia Estatal de Investigación PID2020-114977RB-I00 Fundació la Marató de TV3 202030 "la Caixa" Foundation LCF/PR/HR20/52400018 "la Caixa" Foundation 100010434 |
| Drets: | Aquest 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.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Motion sickness ; Vestibular ; CCK neurons ; Malaise ; Optogenetics |
| Publicat a: | Proceedings of the National Academy of Sciences of the United States of America, Vol. 120 (october 2023) , ISSN 1091-6490 |
