The long-term goal of my research is to understand fundamental structure-function relationships in the cochlea of terrestrial mammals. Hair cell loss and stereocilia pathology can be found in cochlear regions where hearing is impaired, but not always. Afferent terminals on inner hair cells (IHC), however, undergo acute structural changes in response to noise, but the long-term effects on innervation density and synaptic morphology, and their implications for hearing are unknown. This study will first establish a frequency-place map for the C57BL/6J mouse cochlea, which will enable us to make structure-function correlations in the subsequent experiments. At present there is no conclusive map for any mouse strain. Using retrograde tracer injections into defined frequency regions of the cochlear nucleus, we will plot auditory nerve afferent projections into the organ of Corti. Once a frequency map is available, we will characterize the morphology, density, and organization of nerve terminals on IHCs at specific frequency locations (e.g. 16kHz) using electron microscopic analyses of serial sections. We will combine this analysis with an unbiased stereological protocol developed to use only a fraction of the sections for accurate and efficient study of synaptic morphology in several animals. Lastly, we will test the hypothesis that noise damage has a detrimental long term effect on the structure of afferent terminals and their synapses with IHCs, and that these changes are associated with permanent hearing loss.
This aim will study the effects of noise on structure of the IHC-afferent interface at frequency locations corresponding to permanent threshold shift, using stereological techniques developed in the 2nd aim. The mouse is a useful model for auditory neuroanatomy because its small size makes for efficient microscopic analysis, and its genome is indispensable for transgenic and mutant creations. A better understanding of normal and abnormal synaptic structure at IHCs may provide new insights into the mechanisms of hearing loss and will increase opportunities for discovery and for the development of new therapies.
|Muniak, Michael A; Ryugo, David K (2014) Tonotopic organization of vertical cells in the dorsal cochlear nucleus of the CBA/J mouse. J Comp Neurol 522:937-49|
|Muniak, Michael A; Rivas, Alejandro; Montey, Karen L et al. (2013) 3D model of frequency representation in the cochlear nucleus of the CBA/J mouse. J Comp Neurol 521:1510-32|
|Lauer, Amanda M; Fuchs, Paul A; Ryugo, David K et al. (2012) Efferent synapses return to inner hair cells in the aging cochlea. Neurobiol Aging 33:2892-902|
|Francis, Howard W; Rivas, Alejandro; Lehar, Mohamed et al. (2006) Efficient quantification of afferent cochlear ultrastructure using design-based stereology. J Neurosci Methods 150:150-8|
|Stamataki, Sofia; Francis, Howard W; Lehar, Mohamed et al. (2006) Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice. Hear Res 221:104-18|