Prominent expression of Narp in central vestibular pathways: selective effect of labyrinth ablation

Recent in vitro studies demonstrated that Narp, a secreted immediate early gene (IEG) product, induces AMPA receptor clustering. Accordingly, Narp has been implicated in mediating activity-dependent changes in synaptic efficacy. To help define the role of Narp in vivo, we conducted immunohistochemical studies of Narp in rat brain. Unexpectedly, we found robust Narp expression in several discrete areas linked to the vestibular system: the anterodorsal nucleus (ADN) of the thalamus, which relays head orientation information to the cortex, the lateral vestibulospinal (Deiters') nucleus and Purkinje cells in the flocculonodular lobe of the cerebellum. Although strong Narp expression in Deiters' nucleus and the cerebellum was present consistently, Narp expression in the ADN displayed a high degree of variability among animals. To check if this variability in ADN Narp expression reflects its dependence on fluctuating levels of vestibular input, we monitored Narp immunostaining following bilateral labyrinth ablation. This procedure significantly suppressed Narp immunostaining in the ADN, indicating that it is stimulated by naturally occurring vestibular input. In contrast, labyrinth ablation did not affect Narp staining in Deiters' nucleus or the flocculonodular lobe of the cerebellum, presumably because these areas are driven by inputs from multiple systems. As previous studies implicate Narp in synaptic plasticity, these findings suggest that this IEG may mediate ongoing adjustments in synaptic strength or connectivity in several pathways linked to the vestibular system.