Effects of Pre-flocculectomy on Fos Expression and NMDA Receptor-mediated Neural Circuits in the Central Vestibular System after Unilateral Labyrinthectomy

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Abstract
In this study in order to elucidate the role of the flocculus in the whole process of vestibular compensation from the very early stage to the chronic stage, we first examined unilateral labyrinthectomy (UL)-induced spontaneous nystagmus (SN), a behavioral marker of vestibular compensation, and Fos expression, a marker of neural activity, in the vestibular brainstem in pre-unilateral flocculectomized (pre-UF) rats. UL in pre-UF rats caused more severe vestibulo-ocular deficits at the very early stage than it did in floccular-intact rats. Fos expression occurred in the medial vestibular nucleus contralateral to the UL side (contra-MVe) and the prepositus hypoglossal nucleus ipsilateral to the UL side (ipsi-PrH), whereas Fos expression was never seen after UL in floccular-intact rats. Therefore, these findings suggest the UL in pre-UF rats activates the contra-MVe and ipsi-PrH neurons and causes great imbalance between intervestibular nuclear activities, inducing more severe vestibular symptoms at the very early stage than those in floccular-intact rats. Next, we observed MK801 (a specific antagonist on the NMDA receptor)-induced SN in pre-UF rats at the chronic stage after UL. MK801 administration to pre-UL rats caused reappearance of SN even 14 days after UL, while administration to floccular-intact rats at a post-UL interval of 14 days never induced decompensation. Therefore, these findings suggest that the flocculus takes part in NMDA receptor-mediated neural circuits involved in vestibular compensation and modifies the neural interactions at the chronic stage after UL. Taken together, those results suggest that the flocculus plays important roles in the restoration of a balance between intervestibular nuclear activities, to reduce vestibular symptoms during the very early stage, and thereafter in the modification of NMDA receptor-mediated neural interactions in the central vestibular system at the chronic stage.