RT Journal Article SR Electronic T1 Long-lasting visuo-vestibular mismatch in freely-behaving mouse reduces the vestibulo-ocular reflex and leads to neural changes in the direct vestibular pathway JF eneuro JO eneuro FD Society for Neuroscience SP ENEURO.0290-16.2017 DO 10.1523/ENEURO.0290-16.2017 A1 Julie Carcaud A1 Filipa França de Barros A1 Erwin Idoux A1 Daniel Eugène A1 Lionel Reveret A1 Lee E. Moore A1 Pierre-Paul Vidal A1 Mathieu Beraneck YR 2017 UL http://www.eneuro.org/content/early/2017/01/16/ENEURO.0290-16.2017.abstract AB Calibration of the vestibulo-ocular reflex (VOR) depends on the presence of visual feedback. However, the cellular mechanisms associated with VOR modifications at the level of the brainstem remain largely unknown. A new protocol was designed to expose freely-behaving mice to a visuo-vestibular mismatch during a two-week period. This protocol induced a 50% reduction of the vestibulo-ocular reflex (VOR). In vivo pharmacological experiments demonstrated that the VOR reduction depends on changes located outside the flocculus/paraflocculus complex. The cellular mechanisms associated with the VOR reduction were then studied in vitro on brainstem slices through a combination of vestibular afferent stimulation and patch-clamp recordings of central vestibular neurons. The evoked synaptic activity demonstrated that the efficacy of the synapses between vestibular afferents and central vestibular neurons was decreased. In addition, a long-term depression protocol failed to further decrease the synapse efficacy, suggesting that the VOR reduction might have occurred through depression-like mechanisms. Analysis of the intrinsic membrane properties of central vestibular neurons revealed that the synaptic changes were supplemented by a decrease in the spontaneous discharge and excitability of a subpopulation of neurons. Our results provide evidence that a long-lasting visuo-vestibular mismatch leads to changes in synaptic transmission and intrinsic properties of central vestibular neurons in the direct VOR pathway. Overall, these results open new avenues for future studies on visual and vestibular interactions conducted in vivo and in vitro.Significance Statement: Calibration of the vestibulo-ocular reflex depends on the presence of visual feedback. In vivo work suggested that cerebellar-dependent calibration of VOR is in the long-term consolidated in the brainstem. However the associated cellular mechanisms remain unknown. To address these mechanisms, we present an innovative protocol in which freely-behaving mice are submitted to 15 days of visuo-vestibular mismatch. We demonstrated that this protocol leads to a 50% reduction of the VOR. We also showed that in brainstem slices, long-term VOR reduction is associated with synaptic and intrinsic changes within the vestibular nuclei, in the direct VOR pathway. This study opens new avenues for future studies on visual and vestibular interactions conducted both in vivo and in vitro.