.) The overall objective of the proposed research is to investigate central nervous system adaptation in the vestibulo-ocular reflex (VOR). Adaptive changes in VOR gain occur when mismatch of the visual and the vestibular signals causes images to slip on the retina during head movements. It is the purpose of this proposal to investigate anatomical and pharmacological substrates of adaptive VOR gain changes. The overall objective of the proposed research is to test if the anatomical loci and neurochemical mechanisms are the same or different for short and long term adaptation of the VOR. Since the applicant's previous studies in the goldfish have shown that there is a recovery of adaptive function after cerebellectomy, he will examine whether similar mechanisms underlie the VOR adaptive gain changes that take place after long term chronic cerebellectomy. To explore the pharmacology of the system, he will apply compounds related to noradrenergic and excitatory amino acid function. These compounds will be applied diffusely and then locally within discrete regions of the brain. These compounds, which include agonists and antagonists of norepinepherine, NMDA and quisqualate, are thought to have an influence on neuroplastic changes in a number of different structures and systems in the central nervous system. An additional dimension of the study is the use of temperature changes as a means of dissecting out baseline and adaptively altered components of the VOR. Since a decrease in temperature has been shown to inactivate reversibly a recently modified VOR, the investigator will use temperature as an independent variable to test for similarities or differences in the mechanisms responsible for VOR adaptation under the various conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001094-03
Application #
2126259
Study Section
Hearing Research Study Section (HAR)
Project Start
1991-04-01
Project End
1995-07-14
Budget Start
1993-04-01
Budget End
1995-07-14
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Temple University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Carter, Troy L; McElligott, James G (2005) Cerebellar AMPA/KA receptor antagonism by CNQX inhibits vestibuloocular reflex adaptation. Exp Brain Res 166:157-69
McElligott, J G; Beeton, P; Polk, J (1998) Effect of cerebellar inactivation by lidocaine microdialysis on the vestibuloocular reflex in goldfish. J Neurophysiol 79:1286-94
Console-Bram, L M; Baird, D H; Fitzpatrick-McElligott, S G et al. (1998) Modulation of GAP-43 mRNA by GABA and glutamate in cultured cerebellar granule cells. Brain Res 783:316-25
Console-Bram, L M; Fitzpatrick-McElligott, S G; McElligott, J G (1996) Distribution of GAP-43 mRNA in the immature and adult cerebellum: a role for GAP-43 in cerebellar development and neuroplasticity. Brain Res Dev Brain Res 95:97-106
Li, J; Smith, S S; McElligott, J G (1995) Cerebellar nitric oxide is necessary for vestibulo-ocular reflex adaptation, a sensorimotor model of learning. J Neurophysiol 74:489-94
McElligott, J G; Weiser, M; Baker, R (1995) Effect of temperature on the normal and adapted vestibulo-ocular reflex in the goldfish. J Neurophysiol 74:1463-72
Parry, T J; McElligott, J G (1993) A method for restraining awake rats using head immobilization. Physiol Behav 53:1011-5