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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY012232-01A2
Application #
6194079
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Hunter, Chyren
Project Start
2000-08-04
Project End
2004-05-31
Budget Start
2000-08-04
Budget End
2001-05-31
Support Year
1
Fiscal Year
2000
Total Cost
$213,000
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Neurology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Li, Chunyan; Fitzgerald, Malinda E C; Del Mar, Nobel et al. (2015) The identification and neurochemical characterization of central neurons that target parasympathetic preganglionic neurons involved in the regulation of choroidal blood flow in the rat eye using pseudorabies virus, immunolabeling and conventional pathway Front Neuroanat 9:65
Xiao, Jianfeng; Vemula, Satya R; LeDoux, Mark S (2014) Recent advances in the genetics of dystonia. Curr Neurol Neurosci Rep 14:462
Li, Chunyan; Fitzgerald, Malinda E C; Ledoux, Mark S et al. (2010) Projections from the hypothalamic paraventricular nucleus and the nucleus of the solitary tract to prechoroidal neurons in the superior salivatory nucleus: Pathways controlling rodent choroidal blood flow. Brain Res 1358:123-39
Xiao, Jianfeng; Ledoux, Mark S (2005) Caytaxin deficiency causes generalized dystonia in rats. Brain Res Mol Brain Res 141:181-92
Gong, Suzhen; DeCuypere, Michael; Zhao, Yu et al. (2005) Cerebral cortical control of orbicularis oculi motoneurons. Brain Res 1047:177-93
Jiao, Yan; Yan, Jian; Zhao, Yu et al. (2005) Carbonic anhydrase-related protein VIII deficiency is associated with a distinctive lifelong gait disorder in waddles mice. Genetics 171:1239-46
Xiao, Jianfeng; Gong, Suzhen; Zhao, Yu et al. (2004) Developmental expression of rat torsinA transcript and protein. Brain Res Dev Brain Res 152:47-60
Cuthbertson, Sherry; LeDoux, Mark S; Jones, Seth et al. (2003) Localization of preganglionic neurons that innervate choroidal neurons of pterygopalatine ganglion. Invest Ophthalmol Vis Sci 44:3713-24
LeDoux, Mark S; Brady, Kimberly A (2003) Secondary cervical dystonia associated with structural lesions of the central nervous system. Mov Disord 18:60-9
Gong, Suzhen; LeDoux, Mark S (2003) Immunohistochemical detection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). J Neurosci Methods 126:25-34

Showing the most recent 10 out of 14 publications