学习记忆取决于活动依赖的突触传递效率改变。已知下丘脑分泌的神经肽orexin可影响海马突触的可塑性，但对其调控前庭系统长时程突触可塑性的研究还很少。我们发现：1）orexin可兴奋成年大鼠前庭神经元，并调控动物经前庭介导的运动行为；2）前庭核促离子受体相关的突触可塑性细化对出生后空间定向拓扑图和重力探测行为的形成至关重要。我们推测：1）orexin可调控前庭核的突触可塑性，并导致相应的动物行为表达；2）在动物出生后发育的某个特定阶段，下调下丘脑orexin能神经元的分泌或扰乱前庭核orexin能神经传入，会影响前庭-橄榄-小脑神经环路的形成和与前庭相关的行为表达。我们拟研究动物新生期扰乱orexin能系统对重塑空间定向拓扑图和对前庭相关的动物空间定位识别和空间导航学习的影响。研究结果将阐明orexin调控前庭功能发育过程中活动依赖性突触可塑性机制，为治疗突触传递紊乱疾病提供治疗策略。

Learning and memory highly depend on activity-dependent change in synaptic efficacy. Orexin, a hypothalamic neuropeptide, is known to mediate hippocampal synaptic plasticity and is implicated in motor control. However, how orexin modulates long-term synaptic plasticity of the vestibular system remains unclear. Recently, we discovered that orexin excites neurons in the brainstem vestibular nucleus (VN) and regulates vestibular-related motor function of adult rats. Moreover, we made novel observation that refinement of ionotropic receptor-associated synaptic plasticity in VN network is crucial for postnatal establishment of spatial map and for emergence of gravity detection behavior. These therefore provide our team with an edge to hypothesize that orexin regulates the induction of synaptic plasticity in VN neurons that contribute to the expression of vestibular-related behaviors. We further hypothesize that perturbation of orexin neurons/synapses during restricted period of postnatal development deters the formation of neural network in the vestibulo-olivo-cerebellar pathway and the manifestation of vestibular-related behaviors. We therefore aim to address the effect of neonatal perturbation of the orexinergic system in remodeling the spatial map, as revealed by robust linear acceleration. The consequential effect of such drug-delivery paradigm on vestibular-related behaviors, including recognition of spatial orientation and learning of spatial navigation, will also be evaluated. Results will highlight how neuromodulators tune activity-dependent synaptic plasticity in the maturation of vestibular functions, thereby offering a platform for therapeutic strategies that could rescue synaptic disorders.