This project will examine how specific neuronal connections are established between vestibular sensory organs and their central nervous system targets. In adult vertebrates, primary vestibular afferent axons serving the different vestibular end organs form distinct though overlapping regions of axonal arborization in the vestibular nuclei. While the presumed role of this specific connectivity in sensory processing is obvious, little is known about the developmental mechanisms that are responsible for its establishment. The proposed experiments will be a first step towards analyzing the development of organotopic specificity in the primary vestibular afferent projection to the vestibular nuclei. Vital-dye fiber-tracing techniques will be used to label populations or single axons in the zebrafish, Brachydanio rerio. In the initial experiments, the pattern and extent of axonal growth from each vestibular sensory organ in young zebra fish will be examined in fixed specimens both in whole-mounts using confocal microscopy and in cryostat sections. In addition, the dynamic rearrangements of axons in each projection will be studied in living animals using confocal and low light level video microscopy. Such direct observations will establish the normal time-course of axonal patterning, and permit simple perturbation experiments that will test the relative roles of axon-axon and axon-target interactions in forming specific connections. These experiments will be the first to follow the development of the neuronal connections that subserve vestibular senses. At present, little is known about the relative roles of inherent positional labels, environmental influences and patterns of neuronal activity in the formation of the specific neural connections. It is not clear to what extent the lessons learned from studies of the visual system can be applied to the vestibular system. Thus, without such knowledge of vestibular development, it is difficult if not impossible to completely understand its improper development observed in birth defects or its abnormal function after trauma.
