Visualization of muscarinic receptor-mediated phosphoinositide turnover in the hippocampus of young and aged, learning-impaired long evans rats

Hippocampal receptor-mediated phosphoinositide (PI) turnover is severely blunted in aged rats that demonstrate cognitive deficits in the Morris water maze. To further examine the anatomical localization of this deficit, we examined the topography of muscarinic receptor-mediated PI turnover in young and aged-learning impaired rats by taking advantage of an autoradiographic method that visualizes PI turnover by measuring the diacylglycerol (DAG) branch of the PI turnover signal transduction system. Using this method, muscarinic cholinergic receptors were stimulated in hippocampal slices with agonist, and the receptor-mediated incorporation of [³H]cytidine into [³H]CDP-DAG was subsequently quantified in subregions of the hippocampus using film autoradiography. Our results show a significant decrease in basal incorporation of [³H]CDP-DAG in the subiculum and in the dentate gyrus in the aged rats. The muscarinic receptor-mediated [³H]CDP-DAG response was significantly blunted in the aged rats in subiculum, CA3, and CA1. In contrast, the receptor-mediated response was maintained in the dentate gyrus and hilus. These results indicate that the age-associated impairment in receptor-mediated PI turnover differs regionally, with a reduction in the subiculum and hippocampus proper that is pronounced relative to the hilus and dentate gyrus.