Structure and function of the medial superior olive

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DESCRIPTION (provided by applicant): Binaural hearing plays a key role in the development of speech and language perception because the normal development of the brain's binaural circuitry requires the proper activation of these inputs. Besides being instrumental in the development of normal circuitry, recent evaluations of bilateral cochlear implant patients indicates that their newly acquired binaural inputs provide some improvements in their abilities to localize sound and to understand speech in quiet and in the presence of noise. Thus, although we are able to process complex auditory stimuli like speech with only one ear, binaural cues provide additional critical information. Unfortunately it is only "some" improvement for some of these bilateral cochlear implant patients. We are still in the infancy stages of knowing how to optimally present such stimuli to the hard of hearing or deaf via hearing aids or cochlear implants. One of the major impediments on this path is that we still do not have a complete understanding the basic brainstem circuitry involved in binaural processing and the mechanisms used by this circuitry to extract the critical auditory cues. The medial superior olive (MSO) is a brainstem auditory nucleus and the first binaural site in the auditory pathway where major inputs activated by the two ears converge. It is by far the most prominent of the auditory brainstem nuclei in the human superior olivary complex. Interestingly, virtually all children with autistic spectral disorder (ASD) have auditory related dysfunction and the MSO is the most severely and consistently malformed brainstem nucleus in the autistic brain. All of these observations would indicate that a more thorough understanding of MSO structure and function is critical if we are to design appropriate methods of activating this nucleus under compromised conditions. Such efforts in experiments using animals with auditory brainstems similar to humans have been hampered by several features that make it extremely difficult to access and record from cells in the MSO. We have perfected methods that bypass these unfavorable features of the nucleus and will allow us to unequivocally evaluate the anatomical and physiological features of MSO cells that are vital in their binaural mission. The method involves recording the responses of these cells to auditory stimulation not from their cell bodies but remotely from their axons at some distance from the nucleus. After determining the response features to auditory stimuli presented to one or both ears we can inject a mobile dye (Neurobiotin) into the individual axon which fills the entire cell body, dendritic tree and axon collateral field. This gives us the opportunity to evaluate the important anatomical features of these physiologically characterized cells at the light and electron microscopic level as well. It is our sincere belief that the experiments proposed here will provide critical information that will advance our understanding of hearing mechanisms in the normal brain and how to better facilitate hearing in the aged and damaged brain.