ANIMAL NEUROANATOMY

中听老年性耳聋的神经解剖学基础有

The neuroanatomical basis of presbycusis in the central auditory system has not been extensively studied, nor has it been extensively related to neurophysiological findings. Because presbycusis is a human problem, it would be desirable to study its morphological basis in humans. However, morphological study of humans that have had their premortem auditory function well-characterized behaviorally and/or physiologically is extremely difficult. Thus, animal models of certain aspects of presbycusis, the CBA/J and C57BL/6J strains of mice, have been chosen. The CBA/J strain undergoes presbycusis changes late in its life, like the human, but over the full frequency range. The C57BL/6J strain shows hearing losses early in life that progress rapidly in severity. The losses begin at high frequencies and progress towards lower frequencies, as in the human. This study will examine neuroanatomical changes in aging with and without hearing loss in mice that have been tested for auditory function behaviorally (acoustic startle reflex) and physiologically (auditory nerve responses and auditory brainstem responses). In order to evaluate the age- related changes in the morphology of the peripheral auditory system, we will determine the amount of hair cell loss and strial atrophy in the cochleas of the two strains of mice and in rats of Project 2. We will study morphological changes in the central nucleus of the inferior colliculus (ICC). It is:1) a region in which frequency and temporal processing of sounds will be investigated physiologically in Project 3,2) the region in which most information from lower brainstem centers collects before being transmitted to thalamus and cortex, and 3) a region in which changes have been reported in aging rodents. Mice of the following ages and strains will be utilized: 1-2, 6-8, and >24 mos for the CBA/J strain and 1-2, 6-8, and 30-32 mos for the C57BL/6J strain. Morphological studies of the ICC in aging with and without hearing loss fall into three categories: 1) integrity, 2) changes in connectivity, and 3) changes in the morphology of inhibitory neurotransmitter systems. All morphological studies will subdivide the ICC based upon its tonotopic organization into high and low frequency regions. Integrity of the ICC will be determined by measuring numbers and sizes of neurons and the volume of the ICC at the light microscopic level, and by describing changes in neuronal morphology at the electron microscopic level. HRP-injected mice, studied in Project 3 with single-unit physiological techniques, will be used to map physiological functions to anatomical locations in the ICC. Connectivity of the ICC will be determined by quantifying dendritic extent in Golgi- impregnated material, and quantifying synaptic numbers and sizes in electron microscopic material. The numbers and sizes of afferent cell bodies and numbers of efferent terminals, visualized with HRP injections of the ICC, will be quantified. Also in the C57BL/6J mice, reorientation of dendritic trees and reorganization of HRP-filled afferents will be studied to identify the morphological basis of the age-related tonotopic reorganization of the ICC. Morphological correlates of inhibitory function in the ICC will be studied immunohistochemically in material stained for the neurotransmitter systems of GABA and glycin. Numbers of immunohistochemically stained terminals and cell bodies and sizes of cell bodies will be quantified. Additionally, a limited number of morphological studies will be performed in the superior olivary complex (SCC) one of the major inputs to the ICC. These studies will include the measurement of numbers and sizes of neurons in Nissi-stained material and in immunohistochemically stained material, as a function of the morphologically identifiable subnuclei of the SOC.