Modulatory effects of orexin on the functional maturation of central vestibular system in motor coordination and spatial recognition

Abstract

Orexin is a hypothalamic neuropeptide that is known to be involved in animals’ balance and motor coordination. To test whether neonatal perturbation of orexinergic synapses in the vestibular nucleus (VN) exerts any effect on the maturation of vestibular-related behaviors, we blocked/activated orexin receptors in the VN of postnatal day (P) 1 rats by implanting polymer (Elvax) slices loaded with orexin receptor antagonist (SB334867) or agonist ([Ala11, D-Leu 15]-orexin-B) onto the dorsal surface of VN for slow release of the drug to the underlying VN. Specific behavioral tests including negative geotaxis (a graviceptive response), surface righting (ability to correct body orientation to erect position) and air righting were performed on these rats at different stages of postnatal development until adulthood. Neonatal treatment with antagonist accelerated acquisition of negative geotaxis and surface righting from P7 to P6, as well as air righting from P21 to P16. In contrast, neonatal treatment with agonist delayed acquisition of negative geotaxis by 4 days and surface righting by 1 day. These findings reveal the unique role of orexin on functional maturation of the vestibular system. Moreover, neonatal treatment of the VN with agonist impaired the performance of both motor coordination (as revealed by rotarod test and balanced beam test) and spatial navigation (as indicated by dead reckoning/ path integration) at the adult stage. On the contrary, antagonist treatment enhanced the performance in spatial navigation. These findings suggest that neonatal modulation of orexinergic transmission in the neonatal VN perturbs the maturation of spatial recognition. [Supported by NSFC/RGC N_HKU 735/14]