Analysis of noradrenergic transmission in in vitro slices and in oculo grafts

At the present time much is known about the effects of norepinephrine in the central nervous system yet many questions still remain to be answered. Norepinephrine has been shown to have direct effects, modulatory effects, and hormonal effects in different brain regions. The purpose of this thesis was to take one brain region, the hippocampus, and use it to further our understanding of the manner in which noradrenergic innervation might alter its activity. It was of particular interest whether the effects of synaptically released norepinephrine mimicked the effects of exogenous application of norepinephrine.; The first portion of the thesis utilized the in vitro hippocampal slice preparation to determine which alpha-adrenergic receptor mediated the inhibitory effect of norepinephrine on the pyramidal cells. The conclusion from these studies was that the alpha{dollar}sb1{dollar}-receptor was activated during the inhibition of evoked potentials in the hippocampus by norepinephrine. In the second portion of the thesis the effects of synaptically released norepinephrine were studied in in oculo hippocampus/locus coeruleus co-transplants. Preliminary studies characterized some of the physiology and pharmacology of the single hippocampus and locus coeruleus in oculo transplants. The postsynaptic effects in the hippocampus of electrical stimulation of the locus coeruleus in co-transplants mimicked the effects of norepinephrine on pyramidal cells in the in vitro hippocampal slice preparation. High performance liquid chromatography analysis of catecholamine levels confirmed the innervation of the hippocampus by the locus coeruleus in oculo. In oculo hippocampal transplants exhibited 'normal' densities of alpha{dollar}sb1{dollar}- and beta-adrenergic receptors measured with quantitative autoradiography which were upregulated in denervated transplants. Receptor densities measurements without receptor localization and/or measurements of second messenger systems were not found to be good predictors of the pharmacology of the in oculo locus coeruleus-hippocampal connection.