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.
Showing the most recent 10 out of 14 publications
