DEVELOPMENT OF SOUND LOCALIZATION

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This is a request for a Research Career Development Award to address how time coding arises during the development of the auditory system. The analysis of temporally ordered inputs is integral to processing both sound location information and communication signals such as speech. Mechanisms of time coding may be particularly accessible in the bird's auditory brainstem. In birds, auditory nerve fibers enter the brain and divide to terminate in the cochlear nucleus angularis and the cochlear nucleus magnocellularis. The projection from the nucleus magnocellularis to the nucleus laminaris supports the encoding and measurement of interaural time differences. In the nucleus laminaris, the magnocellular axons form delay liens to create maps of interaural time differences which are tapped by postsynaptic coincidence detectors. During the first few weeks of life, the young bird's head more that doubles in size, subjecting it to changing interaural cues. The myelination of the magnocellular delay lines within the nucleus laminaris occurs late in development, during this period of maximum head growth. Since the late myelination of the delay line circuit is functionally significant, we will examine athe developmental profile of myelin genes and the factors that regulate their expression in the brainstem auditory nuclei. Research training support is requested for these experiments. Our intention is to compare the timing of this gene expression with the physiological and anatomical maturation of the delay line circuit. In parallel with the studies of myelination, we will also examine the development of time coding during the tuning and assembly of the map of interaural time differences. The neurons in the nucleus magnocellularis and laminaris encode the timing of the auditory stimulus. We will determine how this time coding develops. In the adult bird, nucleus laminaris neurons are maximally excited by simultaneous activation of their ipsi- and contralateral inputs, via a coincidence detection mechanism. Since the timing of the presynaptic inputs is critical to coincidence detection, we will determine when the "correct" timing of the inputs is achieved. The mechanism underlying the tuning of these inputs is of general interest, since many models of development depend upon selection of temporally ordered input. The proposed research depends heavily on labor intensive physiology experiments. Receipt of an RCD Award would enable me to pursue my long term goal of comparing the timing of myelin-related gene expression with the physiological and anatomical maturation of the delay line circuit. The major deficit in my necessary technical expertise has been molecular biology. It has become essential to know how the system is assembled and modified during development, and what the developmental milestones are. Since delayed myelination of the delay line axons appears to be one of these milestones, support has been requested to improve my molecular biology skills with the assistance of Dr. M. Dubois Dalq at NIH. The award would also give me the necessary time to accomplish my research goals and greatly contribute to my long term scientific enhancement. This application is also supported by the chair of the Zoology department at the University of Maryland.