EYELID SENSORIMOTOR NETWORKS

正常的眼睑运动功能取决于支配眨眼时克隆眼睛的眼轮匝肌和打开眼睛的提睑肌的神经元。传入眼轮匝肌和提睑肌运动神经元的神经结构控制着眼睑自主开合、自发和反射性眨眼以及伴随眼球运动的眼睑活动的参数。自发和反射性眨眼的运动回路对维持正常的眼功能和预防眼损伤至关重要。与异常眨眼相关的神经系统疾病，如眼睑痉挛和开眼睑失用症，可导致严重的功能残疾，包括失明。在神经退行性疾病如进行性核上性麻痹中，眼睑收缩和眨眼频率减少可引起干眼和暴露性角膜炎。眼睑痉挛是继发于眼轮匝肌痉挛性收缩的一种不自主的、典型的双侧闭眼。眼睑痉挛，虽然通常是特发性的，但与中枢神经系统的结构性病变有关，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史，如睑炎或干眼；一种假说认为，对这些刺激的不适应反应对眼睑痉挛的发展至关重要。药理学、生理学和死后病理学证据表明，单胺能系统，特别是5 -羟色胺能，可能在眼睑痉挛的病理生理中起作用。在大鼠和灵长类动物中，使用标准和病毒跨神经元示踪剂对眼轮匝肌和提睑肌运动神经元的运动前神经回路进行解剖学定义。这些实验还将确定眼轮匝肌前运动神经元与来自眼睑和角膜的三叉神经传入神经的中央终点的关系。同时使用两种跨神经元示踪剂将定位对眼轮匝肌和提睑肌运动神经元活动的双侧协调至关重要的神经结构。最后，我们将在大鼠中测定眼轮匝肌运动前网络的组成部分，无论是急性的还是慢性的刺激性眼部刺激。这些实验产生的数据将有助于眼睑运动功能和功能障碍模型的发展，提高对临床眨眼反射测试和眨眼反射条件反射研究的理解，并为病毒进入啮齿动物和灵长类动物神经系统的细胞特异性运输提供重要信息。

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.