BDNF-mediated GABAergic transmission in the rat vestibular nucleus regulates the developmental recognition of spatial orientation

Abstract

Brain-derived neurotrophic factor (BDNF) has been widely implicated in the maturation of GABAergic transmission. We have demonstrated that neonatal rats implanted with BDNF-loaded Elvax slices over the dorsal surface of brainstem vestibular nuclei showed an accelerated re-orientation of body against gravity. We hypothesized that this acceleration caused by BDNF is due to changes in the maturation of GABAergic transmission. To investigate this, long-term changes of inhibitory synaptic transmission were studied using whole-cell patch-clamp experiments in medial vestibular (MV) neurons of rats. We found that these neurons exhibited a developmental change in plasticity from GABAA receptor-mediated inhibitory long-term depression (iLTD) in early developmental stage to inhibitory long-term potentiation (iLTP) in late postnatal stage. In neonatal preparations, BDNF treatment could induce a slight reduction in GABA-mediated current but iLTD was still expressed. In late postnatal preparations, iLTP could no longer be triggered when the brainstem slices were incubated with BDNF. Instead, iLTD, which is indicative of early developmental stages, could be re-induced with BDNF treatment. These results indicate that BDNF modulates the efficacy of GABA synapses through development. Taken together, our data suggest that developmental acquisition of spatial orientation can be modified by BDNF-mediated refinement of neural networks in the vestibular nucleus.