In spite of anatomic and physiologic studies showing a fundamental role for central vestibular structures in the control of posture and movement, little is known abut the neurochemical basis of vestibular function. Acetylcholine may play a transmitter role in vestibular systems as shown by a variety of anatomic, physiologic, biochemical and clinical evidence. I have begun studies of central vestibular cholinergic systems by making lesions of structures with afferent or efferent connections with the vestibular nuclear complex (VNC) and then measuring a cholinergic marker, choline acetyltransferase (CAT), in VNC. Labyrinthectomy, thoracic (T3) cordotomy and vestibular commissurotomy do not affect VNC CAT activity. However, cerebellectomy and injection of kainate into VNC decrease it. I plan to study further a possible vestibulo-cerebellar cholinergic relationship by doing additional selective lesion experiments. For example, I will lesion VNC and measure archicerebellum CAT activity. I will also lesion fastigial nucleus and archicerebellum and measure VNC CAT activity. In addition to this approach, which uses a biochemical marker to study vestibular cholinergic anatomy, I will use a recently developed autoradiographic technique which employs specific retrograde transport of 3H-choline to identify cholinergic neurons. I will use this technique to study vestibulo-cerebellar cholinergic anatomy, and to search for possible reticular and interstitial nucleus cholinergic projections to VNC. Results from these studies are likely to enhance our understanding of the biochemical basis of clinical disorders of movement and posture. Clinical and pathological data suggest involvement of the vestibular nuclei in Parkinson Disease and other parkinsonian syndromes. In addition, we have shown that vestibular mechanisms are involved in a proposed animal model of torsion dystonia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000746-05
Application #
3078111
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1984-09-01
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Saint Hilaire, M H; Burke, R E; Bressman, S B et al. (1991) Delayed-onset dystonia due to perinatal or early childhood asphyxia. Neurology 41:216-22
Park, D H; Kang, U J; Moskowitz, C B et al. (1990) Dopamine beta-hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia. Neurology 40:1626-8
Burke, R E; Cadet, J L; Kent, J D et al. (1990) An assessment of the validity of densitometric measures of striatal tyrosine hydroxylase-positive fibers: relationship to apomorphine-induced rotations in 6-hydroxydopamine lesioned rats. J Neurosci Methods 35:63-73
Burke, R E; Karanas, A L (1990) Demonstration of a medial to lateral gradient in the density of cholinergic neuropil in the rat striatum. Neurosci Lett 108:58-64
Burke, R E; Karanas, A L (1990) Quantitative morphological analysis of striatal cholinergic neurons in perinatal asphyxia. Ann Neurol 27:81-8
Burke, R E; Stark, R I (1989) Asymmetrical perfusion fixation in a rodent model of perinatal hypoxia-ischemia may lead to artifactual morphologic asymmetries. Exp Neurol 103:293-6
Burke, R E; Kang, U J; Jankovic, J et al. (1989) Tardive akathisia: an analysis of clinical features and response to open therapeutic trials. Mov Disord 4:157-75
Burke, R E; Fahn, S (1988) An evaluation of sustained postural abnormalities in rats induced by intracerebro-ventricular injection of chlorpromazine methiodide or somatostatin as models of dystonia. Adv Neurol 50:335-42
Kang, U J; Burke, R E; Fahn, S (1988) Tardive dystonia. Adv Neurol 50:415-29
Burke, R E; Kang, U J (1988) Tardive dystonia: clinical aspects and treatment. Adv Neurol 49:199-210

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