The proposed experiments, would make use of experimental embryology, in vitro brain slices, electrophysiology, light and electron microscopy, and pharmacology, to study how interactions between functionally-linked cells or tissues contribute to development of the nervous system. One group of experiments would examine interactions between axons and their target cells during development of stereotyped patterns of synaptic connections in be brain stem auditory system of chick embryos. Early destruction of the otocyst (embryonic precursor of the inner ear and cochlear nerve) induces formation of an anomalous functional axonal projection connecting the cochlear nuclei on the two sides of the brain. Data on developmental interactions between these abnormal synaptic partners will be compared will previous work on normal development to answer the questions: 1) How does a change in the kind of afferent synaptic input affect the type of postsynaptic excitatory amino acid receptor in the cochlear nucleus? 2) Does the anomalous projection save its target neurons from deafferentation-induced neuronal death? 3) Is the number of afferent axons converging on a given target cell determined by the target or by the afferents?, 4) Is the timing and/or extent of developmental synapse elimination and reduction in afferent branching influenced by the target cells or are they properties of the afferent themselves?, and 5) Are the processes described in (4) dependent upon normal patterns of electrical activity in the afferents? A second group of experiments will use surgical manipulations of the external and middle ear rudiments of chick embryos to produce animals with a very early congenital conductive hearing loss. The effects of this deprivation on the cochlea and cochlear nucleus will be assessed electrophysiologically and morphologically, with the aim of answering two questions: 1) Is cochlear damage required to produce morphological changes in the brain stem auditory nuclei after deprivation?, and 2) Does a purely conductive hearing loss induced early in life ultimately result in early sensorineural hearing loss? It may be quite important for the success of restorative programs for be hearing-disabled to understand the neural changes accompanying early hearing loss. The proposed studies include early manipulations of the external, middle, and internal ears, with subsequent study of structure and function development in an cochlea and brain in an animal whose hearing, like man's, begins well before birth. Thus, the proposed experiments should contribute to a detailed and comprehensive understanding of be effects on auditory system development of early conductive and sensorineural hearing loss.
