Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo

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 repairing 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.
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Raphaelle Cassel, Pierrick Bordiga, Julie Carcaud, François Simon, Mathieu Beraneck, et al.. Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo. Disease Models & Mechanisms, Cambridge Company of Biologists, 2019, 12 (7), pp.dmm039115. ⟨10.1242/dmm.039115⟩. ⟨hal-02352249⟩

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