Spatial orientation can be defined operationally as the ability to align internal spatial vectors with gravito-inertial acceleration (GIA). Accurate alignment of these internal vectors to GIA is critical for balance and maintenance of gaze during locomotion, and plasticity is necessary to correct imbalances. The central themes of the Program Project are to understand the neural basis for spatial orientation and plasticity in the vestibular system. A multifaceted approach will be used that includes modeling, human and animal behavioral studies, single unit analysis, and molecular studies of neurotransmission. The proposed Program Project consists of two model-based behavioral and single unit studies in the monkey and rabbit to determine how spatial orientation is controlled by the nodulus and uvula. This will be done by comparing the dynamics of unit activity to those of eye velocity during tilts of gravitoinerial acceleration vector, by doing comparative behavior studies in these frontal and lateral eyed animals, and in determining how focused lesions in various parts of the zonal structure of the nodulus and uvula affect orientation vectors of velocity storage. A molecular/anatomical study will focus on nitric oxide and related molecules as well as on excitatory amino acid receptors involved during developmental in the vestibular system and in adaptation of parameters related to spatial orientation and gain control in the vestibulo-ocular reflex (VOR). A fourth study will determine how spatial orientation is manifest in the eye and head movements of freely moving human subjects with and without velocity storage during angular locomotion. Two core modules will support research in all of the projects. Through this study of spatial orientation and plasticity in the VOR, it is anticipated that important insights will be obtained about how information related to the GIA vector is coded and adapted by the vestibulo-cerebellum and vestibular nuclei, what role this coding plays in maintenance of posture and balance during locomotion, and how locomotion and maintenance of gaze is disordered when orientation to the GIA is disturbed.