The overall aim of the proposed studies is to further elucidate the ultrastructural neurochemical anatomy and interconnections of the septo- hippocampal complex. These studies will aid our understanding of mnemonic functions and human diseases, particularly Alzheimer's disease and temporal lobe epilepsy. Additional analyses of the intrinsic and extrinsic connections of the sexually dimorphic and estrogen/androgen sensitive septal complex, particularly with the syndrome and in understanding how the neuroendocrine and cognitive/associational areas of the central nervous system interact. While there are major differences between the human and rodent hippocampal formations, these structures are very similar in the human and monkey brain. Therefore, in addition to rat studies, we propose to continue the analysis of the hippocampal formation of subhuman primates. Two major lines of inquiry are proposed: a) why some hippocampal neurons and areas are more seizure sensitive than others; and b) how the septal complex mediates bidirectional information between the hippocampus and the neuroendocrine hypothalamus. By using interlinked state-of-the-art morphological techniques, including correlated light and electron microscopic double immunostaining methods, antero and retrograde tracer techniques, and Golgi impregnation, as well as by combining electrophysiological and histochemical methods, the following studies are suggested: 1. Further analysis of the synaptology and transmitter content of seizure-sensitive and seizure-resistant neurons in the rat and monkey hippocampal formation. 2. Neurochemistry of interneurons associated with identified mossy cells. 3. Further characterization of extrinsic hippocampal substance P and calretinin systems. 4. Synaptology and neurochemistry of subcortical circuitries controlling septal area neurons and the septo-hippocampal pathway.
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