The overall objective of this proposal is to gain a better understanding of the organization of somatostatin (SOM) containing neurons in areas of the non-human primate hippocampal formation, a set of structures though to be homologous with regions of the human limbic cortex that are profoundly affected in Alzheimer's disease. Our experimental hypothesis is that hippocampal formation neurons containing SOM, a putative neurotransmitter known to decline in AD, may occupy a pivotal position in cortical and limbic neural circuitry, so that their deterioration would contribute to the phenomena of cortical and hippocampal disconnection in AD. The specific goals of this proposal will determine the distribution of SOM neurons in the hippocampal formation, whether these SOM containing neurons exhibit features of local circuit neurons, whether they are located predominantly in cortical layers containing long projection neurons, whether SOM neurons serve as interneurons or projection neurons of both, whether the laminar organization of SOM immunoreactive fibers matches the distribution of SOM receptors, and whether SOM neurons exhibit age-related changes in the hippocampal formation. The planned studies will utilize immunohistochemistry using SOM poly clonal antibodies, NADPH-histochemistry, horseradish peroxidase retrograde tracer histochemistry combined with SOM immunohistochemistry, receptor autoradiography and computer assisted morphometric analysis of SOM neurons. Anatomical studies of the neural circuitry of non-human primate cortical regions homologous to areas affected in AD have provided basic information needed to better understand the meaning of the cortical distribution of plaques and tangles seen in AD. The information gathered from this proposal will ad to our knowledge or cortical circuitry and will provide new data relevant to neurological disorders and mental health.
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