Behavioral expression of orexin-modulated transmission in the vestibular nucleus of postnatal rats

Abstract

Orexin is known to participate in body balance and motor coordination via modulating synaptic transmission in the central vestibular system of adult animals. We hypothesize that orexin also regulates the maturation of vestibular functions during postnatal development. To test whether neonatal perturbation of orexinergic synapses in the vestibular nucleus (VN) exerts any effect on the acquisition of vestibular-related behaviors, we blocked or activated orexin receptors in the VN of postnatal day (P) 1 rats by implanting drug-containing Elvax slice onto the dorsal surface of VN for slow release of the drug to the underlying VN. Pharmacological intervention was achieved by loading the slices with orexin, orexin receptor antagonist (SB334867) or orexin receptor agonist ([Ala11, D-Leu15]-orexin-B). Specific behavioral tests including negative geotaxis (a graviceptive response), surface righting and air righting were performed on these rats at different postnatal stages until adulthood. Neonatal treatment with orexin receptor antagonist accelerated acquisition of negative geotaxis, surface righting, as well as air righting in the course of early postnatal development. In contrast, neonatal treatment with orexin or its receptor agonist delayed acquisition of negative geotaxis and surface righting. Adult rats pretreated at neonatal stage with orexin receptor agonist or antagonist were further tested for (i) spatial navigation by dead reckoning test; (ii) motor coordination by rotarod test and balance beam test. Treatment with orexin receptor antagonist enhanced the performance of dead reckoning while treatment with agonist impaired the performance of both dead reckoning and motor coordination. Taken together, our findings demonstrated that orexinergic modulation in the VN impacts developmental refinement of neural circuit for vestibular-related behaviors. [Supported by N_HKU735/14]