Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo.
Identifieur interne : 000223 ( Main/Curation ); précédent : 000222; suivant : 000224Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo.
Auteurs : Raphaelle Cassel [France] ; Pierrick Bordiga [France] ; Julie Carcaud [France] ; François Simon [France] ; Mathieu Beraneck [France] ; Anne Le Gall [France] ; Anne Benoit [France] ; Valentine Bouet [France] ; Bruno Philoxene [France] ; Stéphane Besnard [France] ; Isabelle Watabe [France] ; David Pericat [France] ; Charlotte Hautefort [France] ; Axel Assie [France] ; Alain Tonetto [France] ; Jonas Dyhrfjeld-Johnsen [France] ; Jordi Llorens [Espagne] ; Brahim Tighilet [France] ; Christian Chabbert [France]Source :
- Disease models & mechanisms [ 1754-8411 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- physiologie : Synapses, Voies afférentes.
- physiopathologie : Vertige.
- Animaux, Modèles animaux de maladie humaine, Souris.
English descriptors
- KwdEn :
- MESH :
- physiology : Afferent Pathways, Synapses.
- physiopathology : Vertigo.
- Animals, Disease Models, Animal, Mice.
Abstract
Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients.
DOI: 10.1242/dmm.039115
PubMed: 31213478
PubMed Central: PMC6679379
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Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Pericat, David" sort="Pericat, David" uniqKey="Pericat D" first="David" last="Pericat">David Pericat</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Hautefort, Charlotte" sort="Hautefort, Charlotte" uniqKey="Hautefort C" first="Charlotte" last="Hautefort">Charlotte Hautefort</name><affiliation wicri:level="1"><nlm:affiliation>Hôpital Lariboisière, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Lariboisière, 75010 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Assie, Axel" sort="Assie, Axel" uniqKey="Assie A" first="Axel" last="Assie">Axel Assie</name><affiliation wicri:level="1"><nlm:affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Tonetto, Alain" sort="Tonetto, Alain" uniqKey="Tonetto A" first="Alain" last="Tonetto">Alain Tonetto</name><affiliation wicri:level="1"><nlm:affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Dyhrfjeld Johnsen, Jonas" sort="Dyhrfjeld Johnsen, Jonas" uniqKey="Dyhrfjeld Johnsen J" first="Jonas" last="Dyhrfjeld-Johnsen">Jonas Dyhrfjeld-Johnsen</name><affiliation wicri:level="1"><nlm:affiliation>Sensorion, Montpellier, 34000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sensorion, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Llorens, Jordi" sort="Llorens, Jordi" uniqKey="Llorens J" first="Jordi" last="Llorens">Jordi Llorens</name><affiliation wicri:level="1"><nlm:affiliation>Universitat de Barcelona, 08907 Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Universitat de Barcelona, 08907 Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Tighilet, Brahim" sort="Tighilet, Brahim" uniqKey="Tighilet B" first="Brahim" last="Tighilet">Brahim Tighilet</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Chabbert, Christian" sort="Chabbert, Christian" uniqKey="Chabbert C" first="Christian" last="Chabbert">Christian Chabbert</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France christian.chabbert@univ-amu.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31213478</idno><idno type="pmid">31213478</idno><idno type="doi">10.1242/dmm.039115</idno><idno type="pmc">PMC6679379</idno><idno type="wicri:Area/Main/Corpus">000223</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000223</idno><idno type="wicri:Area/Main/Curation">000223</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000223</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo.</title><author><name sortKey="Cassel, Raphaelle" sort="Cassel, Raphaelle" uniqKey="Cassel R" first="Raphaelle" last="Cassel">Raphaelle Cassel</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Bordiga, Pierrick" sort="Bordiga, Pierrick" uniqKey="Bordiga P" first="Pierrick" last="Bordiga">Pierrick Bordiga</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Carcaud, Julie" sort="Carcaud, Julie" uniqKey="Carcaud J" first="Julie" last="Carcaud">Julie Carcaud</name><affiliation wicri:level="1"><nlm:affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Simon, Francois" sort="Simon, Francois" uniqKey="Simon F" first="François" last="Simon">François Simon</name><affiliation wicri:level="1"><nlm:affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Beraneck, Mathieu" sort="Beraneck, Mathieu" uniqKey="Beraneck M" first="Mathieu" last="Beraneck">Mathieu Beraneck</name><affiliation wicri:level="1"><nlm:affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:affiliation>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Le Gall, Anne" sort="Le Gall, Anne" uniqKey="Le Gall A" first="Anne" last="Le Gall">Anne Le Gall</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1075, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1075, Caen</wicri:regionArea></affiliation></author><author><name sortKey="Benoit, Anne" sort="Benoit, Anne" uniqKey="Benoit A" first="Anne" last="Benoit">Anne Benoit</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1075, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1075, Caen</wicri:regionArea></affiliation></author><author><name sortKey="Bouet, Valentine" sort="Bouet, Valentine" uniqKey="Bouet V" first="Valentine" last="Bouet">Valentine Bouet</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1075, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1075, Caen</wicri:regionArea></affiliation></author><author><name sortKey="Philoxene, Bruno" sort="Philoxene, Bruno" uniqKey="Philoxene B" first="Bruno" last="Philoxene">Bruno Philoxene</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1075, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1075, Caen</wicri:regionArea></affiliation></author><author><name sortKey="Besnard, Stephane" sort="Besnard, Stephane" uniqKey="Besnard S" first="Stéphane" last="Besnard">Stéphane Besnard</name><affiliation wicri:level="1"><nlm:affiliation>INSERM U1075, Caen, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1075, Caen</wicri:regionArea></affiliation></author><author><name sortKey="Watabe, Isabelle" sort="Watabe, Isabelle" uniqKey="Watabe I" first="Isabelle" last="Watabe">Isabelle Watabe</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Pericat, David" sort="Pericat, David" uniqKey="Pericat D" first="David" last="Pericat">David Pericat</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Hautefort, Charlotte" sort="Hautefort, Charlotte" uniqKey="Hautefort C" first="Charlotte" last="Hautefort">Charlotte Hautefort</name><affiliation wicri:level="1"><nlm:affiliation>Hôpital Lariboisière, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Hôpital Lariboisière, 75010 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Assie, Axel" sort="Assie, Axel" uniqKey="Assie A" first="Axel" last="Assie">Axel Assie</name><affiliation wicri:level="1"><nlm:affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Tonetto, Alain" sort="Tonetto, Alain" uniqKey="Tonetto A" first="Alain" last="Tonetto">Alain Tonetto</name><affiliation wicri:level="1"><nlm:affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Dyhrfjeld Johnsen, Jonas" sort="Dyhrfjeld Johnsen, Jonas" uniqKey="Dyhrfjeld Johnsen J" first="Jonas" last="Dyhrfjeld-Johnsen">Jonas Dyhrfjeld-Johnsen</name><affiliation wicri:level="1"><nlm:affiliation>Sensorion, Montpellier, 34000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Sensorion, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Llorens, Jordi" sort="Llorens, Jordi" uniqKey="Llorens J" first="Jordi" last="Llorens">Jordi Llorens</name><affiliation wicri:level="1"><nlm:affiliation>Universitat de Barcelona, 08907 Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Universitat de Barcelona, 08907 Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Tighilet, Brahim" sort="Tighilet, Brahim" uniqKey="Tighilet B" first="Brahim" last="Tighilet">Brahim Tighilet</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Chabbert, Christian" sort="Chabbert, Christian" uniqKey="Chabbert C" first="Christian" last="Chabbert">Christian Chabbert</name><affiliation wicri:level="1"><nlm:affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France christian.chabbert@univ-amu.fr.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille</wicri:regionArea></affiliation></author></analytic><series><title level="j">Disease models & mechanisms</title><idno type="eISSN">1754-8411</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Afferent Pathways (physiology)</term><term>Animals (MeSH)</term><term>Disease Models, Animal (MeSH)</term><term>Mice (MeSH)</term><term>Synapses (physiology)</term><term>Vertigo (physiopathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Modèles animaux de maladie humaine (MeSH)</term><term>Souris (MeSH)</term><term>Synapses (physiologie)</term><term>Vertige (physiopathologie)</term><term>Voies afférentes (physiologie)</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Synapses</term><term>Voies afférentes</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Afferent Pathways</term><term>Synapses</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Vertige</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Vertigo</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Modèles animaux de maladie humaine</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31213478</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>05</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>05</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1754-8411</ISSN><JournalIssue CitedMedium="Internet"><Volume>12</Volume><Issue>7</Issue><PubDate><Year>2019</Year><Month>07</Month><Day>15</Day></PubDate></JournalIssue><Title>Disease models & mechanisms</Title><ISOAbbreviation>Dis Model Mech</ISOAbbreviation></Journal><ArticleTitle>Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">dmm039115</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1242/dmm.039115</ELocationID><Abstract><AbstractText>Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients.</AbstractText><CopyrightInformation>© 2019. Published by The Company of Biologists Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cassel</LastName><ForeName>Raphaelle</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bordiga</LastName><ForeName>Pierrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carcaud</LastName><ForeName>Julie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Simon</LastName><ForeName>François</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beraneck</LastName><ForeName>Mathieu</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sorbonne Paris Cité, Université Paris Descartes, 75006 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Gall</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>INSERM U1075, Caen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benoit</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>INSERM U1075, Caen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bouet</LastName><ForeName>Valentine</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>INSERM U1075, Caen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Philoxene</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>INSERM U1075, Caen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besnard</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>INSERM U1075, Caen, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Watabe</LastName><ForeName>Isabelle</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pericat</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hautefort</LastName><ForeName>Charlotte</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Hôpital Lariboisière, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Assie</LastName><ForeName>Axel</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tonetto</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dyhrfjeld-Johnsen</LastName><ForeName>Jonas</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Sensorion, Montpellier, 34000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Llorens</LastName><ForeName>Jordi</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-3894-9401</Identifier><AffiliationInfo><Affiliation>Universitat de Barcelona, 08907 Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tighilet</LastName><ForeName>Brahim</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chabbert</LastName><ForeName>Christian</ForeName><Initials>C</Initials><Identifier Source="ORCID">0000-0003-3932-0223</Identifier><AffiliationInfo><Affiliation>Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France christian.chabbert@univ-amu.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Dis Model Mech</MedlineTA><NlmUniqueID>101483332</NlmUniqueID><ISSNLinking>1754-8403</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000344" MajorTopicYN="N">Afferent Pathways</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013569" MajorTopicYN="N">Synapses</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014717" MajorTopicYN="N">Vertigo</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Excitotoxicity</Keyword><Keyword MajorTopicYN="Y">Plasticity</Keyword><Keyword MajorTopicYN="Y">Synapses</Keyword><Keyword MajorTopicYN="Y">Vestibular disorders</Keyword><Keyword MajorTopicYN="Y">Vestibule</Keyword></KeywordList><CoiStatement>Competing interestsThe authors declare no competing or financial interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>01</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>06</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>6</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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