The neural basis for the generation and control of vertical vestibular-induced eye movements, including adaptive plasticity of the vestibulo-ocular reflex (VOR) will be studied utilizing physiological, morphological, neurochemical, and morphophysiological techniques. The vertical VOR will be visually adapted by employing both miniaturizing and/or magnifying lenses placed in a holder in front of the animals' eyes. Both the normal and adapted VORs will then be utilized as behavioral probes to elucidate the properties of brainstem and cerebellar neurons in vestibulo-ocular pathways. First, we will record extracellularly in alert animals, from Y-group, vestibular nucleus, and cerebellar neurons in normal monkeys and in those whose vertical VOR has been plastically adapted. We will quantify the responses of these cells to ascertain their roles, if any, in the normal VOR. Then, during VOR adaptation, we will ask if there are changes in neuronal firing that parallel the changes in reflex-induced eye movements. We hypothesize that eye movement plasticity is brought about by modified signals transmitted, pre-formed to the extra ocular motor nuclei. Y-group neurons are favorably situated to carry these signals. They are flocculus target neurons that are di- or polysynaptically activated by the VIIIth nerve and they project monosynaptically to the IIIrd and IVth nuclei. Discrete chemical lesions will also be employed in selected nuclear and cerebellar sites to temporarily silence them and then the normal and adapted VORs examined. The synaptic connectivity, morphology, and morphophysiology of neurons will be studied with anatomical tracers and intracellular injection to add information at the cellular and morphological levels that may shed light upon the function of this structure in gaze control. The Marr- Albus-Ito hypotheses and others will be critically tested. The neural basis for the integration of signals related to vertical eye movements will be studied in squirrel monkeys with physiological and morphological techniques. The axons of interstitial nucleus of Cajal neurons will be impaled in alert animals, physiologically characterized in relation to gaze, and injected with tracer to elucidate neuronal structure-function correlations. We will evaluate the organization of the vertical neural integrator to test hypotheses concerning its operation and the necessity for a bilateral structural organization.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005433-14
Application #
2391672
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1983-11-01
Project End
2001-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Heine, Shane A; Highstein, Stephen M; Blazquez, Pablo M (2010) Golgi cells operate as state-specific temporal filters at the input stage of the cerebellar cortex. J Neurosci 30:17004-14
Inagaki, Keiichiro; Heiney, Shane A; Blazquez, Pablo M (2009) Method for the construction and use of carbon fiber multibarrel electrodes for deep brain recordings in the alert animal. J Neurosci Methods 178:255-62