The overall goal of this project is to discover neurochemical correlates of vestibular compensation. A description of such correlates will provide a better understanding of the physiological conditions which are caused by vestibular injury and which parallel vestibular compensation. Such a description may also provide the basis for neurochemical or drug therapy which may benefit a patient's recovery from vestibular injury. Although this proposal utilizes an experimental model of unilateral injury to the peripheral vestibular end organs, the results will also yield evidence pertaining to bilateral injury to the end organs, as well as injury to specific central nervous system regions.
The specific aims of this project are to describe modifications in gamma aminobutyric acid (GABA), (met) and (leu)enkephalin (ENK), glutamate (GLU), acetylcholine (ACh), and turosine hydroxylase (TH) within the squirrel monkey brain: 1) during the course of vestibular compensation; 2) after behavioral reinforcement procedures which accelerate vestibular compensation; 3) after drug reinforcement procedures which accelerate vestibular compensation. In order to detect changes in brain neurochemistry, relative levels of GABA, ENK, GLU, ACh, and TH will be determined by measuring the staining intensity of brainstem sections after immunocytochemical processing. We have previously directly visualized all of these neurochemicals (except for ACh), using immunocytochemical techniques, in the vestibular nuclei of normal squirrel monkeys; ACh has been indirectly visualized using the histochemical reaction for AChE, its associated degradating enzyme. Behavioral reinforcement procedures will include both physical exercise, which stimulates postural rebalance, and optokinetic stimulation, which aids oculomotor rebalance. Drug reinforcement procedures will include injection of the growth hormone, adrenocorticotrophic hormone (ACTH4-10), and the ACh agonist, atrophine, both of which facilitate equilibrium compensation.
