The purpose of this research is to characterize genetic determinants of dendrodendritic local circuit organization. To accomplish this I will study the reorganization of local neuronal circuits in the olfactory bulb following the loss of mitral cells in a neurological mutant strain of mice. Emphasis will be placed upon identifying changes in the dendrodendritic synaptic contacts of the intrinsic olfactory bulb circuits. The responses of axodendritic and axosomatic synapses to the anatomical pertubations found in neurologically mutant mice have been studied elsewhere in the CNS. Comparable analyses of dendrodendritic synaptic appositions are not available. There is a growing awareness of the extensive distribution of dendrodendritic synapses in local circuits throughout the central nervous system. However, the factors which govern their genesis, stabilization and maintenance are not well understood. The proposed program of research will examine these properties by determining the effect of mitral cell loss upon the structural and functional organization of the remaining neurons which comprise the local circuits via dendrodendritic contacts. The research will also provide data pertinent to the controversey surrounding the anatomical and functional role of the olfactory bulb tufted cell which is not affected in this mutant mouse. Several methodological approaches will be employed including light microscopy for neuron counts and reconstruction of dendritic trees; ultrastructural characterization of local circuit synaptic contacts; and electrophysiological analyses of single unit activity to establish the functional status of local circuits. This program of research may ultimately provide information pertinent to clinical examples of accelerated neuronal death such as human senile dementia.
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