Orexin regulates synaptic transmission in the central vestibular system

Abstract

Orexin is known to modulate synaptic plasticity in the hippocampus and contribute to social memory in adult rodents. While orexinergic neurons in the lateral hypothalamus project to the vestibular nucleus (VN), the role of orexin in the maturation of vestibular functions remains unexplored. We hypothesized that orexin modulates synaptic transmission in the VN, thereby regulating the expression of vestibular-related behaviors during postnatal development. Our immunohistochemical results showed that orexin receptors and orexin-immunopositive neurons are present in the VN. Also, pharmacological perturbation of orexin receptors in the VN of neonatal rats led to impairment in developmental acquisition of vestibular-related behaviors such as air-righting reflex. To understand the role of orexin on synaptic transmission in the VN, we employed in vitro whole-cell patch-clamp technique to study the action of orexin on the excitability of neurons in the medial vestibular nucleus (MVN) of rats at postnatal day 14. Treatment with orexin led to reduction in amplitude and frequency of miniature inhibitory postsynaptic current (mIPSC). This suggests that orexin decreases both presynaptic release of inhibitory transmitters and postsynaptic depolarization within the MVN. Notably, we found that agonist of orexin 2 receptor reduced the frequency but not amplitude of mIPSC. We have thus demonstrated that orexin suppresses synaptic inhibition on MVN neurons. We further investigated whether orexin-modulated mIPSC is mediated by GABA-A receptors or glycine receptors. With the use of bicuculline and strychnine, we observed that orexin decreased mIPSC mediated by GABA-A receptors, but not glycine receptors. Taken together, our findings provide us with fundamental knowledge about the modulatory role of orexin in GABAergic transmission within the VN and its impact on postnatal refinement of neural circuit for vestibular-related behavior. [Supported by N_HKU735/14].