Orexin modulates inhibitory synaptic transmission of vestibular nuclear neurons in rats

Abstract

Orexin is a neuromodulator known to be produced by lateral hypothalamic neurons, which send projections to the hippocampus, brainstem and cerebellum. In the hippocampus, orexin is known to modulate long-term synaptic plasticity, thereby contributing to social memory. We hypothesized that orexin modulates synaptic transmission in the vestibular nucleus (VN), thus regulating behavioral expression. To understand the impact of orexin on synaptic transmission within the VN, we employed an established in vitro electrophysiological technique to study the action of orexin on the excitability of neurons in the medial vestibular nucleus (MVN) of rats at postnatal day 14. Whole-cell patch-clamp results indicated that treatment with orexin led to reductions in amplitude and frequency of miniature inhibitory postsynaptic current (mIPSC). This suggests that orexin decreases both the presynaptic release of inhibitory transmitters and postsynaptic depolarization in MVN neurons. We thus demonstrated that orexin attenuates synaptic inhibition on MVN neurons. We further tested whether orexin-modulated mIPSC is mediated by GABAA receptors or glycine receptors. With the use of bicuculline and strychnine, we observed that orexin decreased mIPSC mediated by GABAA receptors, but not glycine receptors. Taken together, our findings provided us with fundamental knowledge about the modulatory role of orexinergic transmission in the VN. This forms the basis for further investigation on the involvement of orexin in long-term synaptic plasticity of the central vestibular system. [Supported by N_HKU735/14]