EYELID SENSORIMOTOR NETWORKS

正常的眼皮运动功能依赖于支配眼轮匝肌的神经元，这些神经元在眨眼时克隆眼睛，并依赖于睁开眼睛的眼睑提肌。眼轮匝肌和提上睑运动神经元的传入神经结构控制着眼皮的自主开闭、自发和反射性眨眼以及伴随眼球运动的眼皮活动。调节自发性和反射性眨眼的运动回路对于维持正常的眼功能和预防眼损伤是至关重要的。与异常眨眼相关的神经系统疾病，如眼睑痉挛和睁开眼皮失用症，可导致严重的功能障碍，包括失明。在神经退行性疾病中，如进行性核上性瘫痪，眼皮退缩和眨眼频率降低会导致干眼和暴露性角膜炎。眼睑痉挛是一种继发于眼轮匝肌痉挛收缩的不自主的、典型的双眼闭合。眼睑痉挛虽然通常是特发性的，但也与中枢神经系统的结构性损害有关，特别是吻侧脑干和中脑。光敏感(畏光)是大多数患者的症状。一些眼睑痉挛患者有刺激性眼部刺激的病史，如眼缘炎或干眼；一种假设是对这些刺激的不适应反应在眼睑痉挛的发展中起关键作用。药理学、生理学和死后病理证据表明，单胺系统，特别是5-羟色胺能系统，可能在眼睑痉挛的病理生理学中发挥作用。大鼠和灵长类动物的眼轮匝肌和提上睑运动神经元的神经回路前运动神经元将使用标准和病毒跨神经元示踪剂进行解剖学定义。这些实验还将确定眼轮匝肌运动前神经元与来自眼皮和角膜的三叉神经传入的中枢终末的关系。同时使用两种跨神经元示踪剂将定位对眼轮匝肌和提眼睑运动神经元活动的双侧协调至关重要的神经结构。最后，将确定大鼠眼轮匝肌运动前网络被刺激性眼睛刺激急性或慢性激活的成分。这些实验所产生的数据将有助于发展眼皮运动功能和功能障碍的模型，增进对临床眨眼反射测试和眨眼反射条件性研究的理解，并提供关于病毒进入啮齿动物和灵长类神经系统的细胞特异性运输的重要信息。

Normal eyelid motor function depends on neurons that innervate the orbicularis oculi muscles that clone the eyes during blinks and levator palpebrae muscles that open the eyes. Neural structures afferent to orbicularis oculi and levator palpebrae motoneurons control the parameters of voluntary eyelid opening and closure, spontaneous and reflexive blinks, and eyelid activity that accompanies eye movements. The motor circuitry mediating spontaneous and reflex blinking is critical for the maintenance of normal ocular function and prevention of ocular injury. Disorders of the nervous system associated with abnormal blinking such as blepharospasm and apraxia of eyelid opening can produce significant functional disability including blindness. Lid retraction and decreased blink frequency seen in neurodegenerative disorders such as progressive supranuclear palsy can cause dry eye and exposure keratitis. Blepharospasm is an involuntary, typically bilateral, closure of the eyes secondary to spasmodic contractions of the orbicularis oculi musculature. Blepharospasm, although usually idiopathic, has been associated with structural lesions of the central nervous system, particularly the rostral brainstem and mesencephalon. Light sensitivity (photophobia) is a symptom with most patients. Some patients with blepharospasm have a history of irritative ocular stimuli such as blepharitis or dry eye; one hypothesis is that maladaptive responses to these stimuli are critical to the development of blepharospasm. Pharmacological, physiological, and postmortem-pathological evidence suggest that monoaminergic systems, particularly serotonergic, may play a role in the pathophysiology of blepharospasm. The neural circuits premotor to orbicularis oculi and levator palpebrae motoneurons will be defined anatomically in both rats and primates using both standard and viral transneuronal tracers. These experiments will also determine the relationship of orbicularis oculi premotor neurons to the central terminations of trigeminal afferents from the eyelid and cornea. The simultaneous use of two transneuronal tracers will localize neural structures critical to the bilateral coordination of orbicularis oculi and levator palpebrae motoneuron activity. Finally, the components of the orbicularis oculi premotor network activated either acutely or chronically by irritative ocular stimuli will be determined in rats. The data generated from these experiments will contribute to the development of models of eyelid motor function and dysfunction, improve understanding of clinical blink reflex testing and conditioning studies of the blink reflex, and provide important information regarding the cell-specific transport of viruses into rodent and primate nervous systems.