Age-dependent changes in projections from locus coeruleus to hippocampus dentate gyrus and frontal cortex

Age-dependent changes in noradrenergic innervations of the hippocampal dent ate gyrus (DG) and the frontal cortex (FC) have been studied in male F344 r ats. The projections from the nucleus locus coeruleus (LC) to DG or FC with advancing age (from 7 to 27 months) in rats have been quantified by electr ophysiological and immunohistochemical methods. In the electrophysiological study, we observed that the percentage of LC neurons activated antidromica lly by electrical stimulation (P-index) of DG or FC decreased with age. We found that the percentage of LC neurons showing multiple antidromic latenci es (M-index), which suggests axonal branching of individual LC neurons, inc reased markedly between 15 and 17 months in DG or FC. In DG, the M-index in creased steadily between 15 and 24 months. In contrast, the increased M-ind ex in FC was maintained until 24 months. The increased M-index in both targ ets declined at 27 months. These results suggest that LC neurons give rise to axonal branching following the loss of projections to DG or FC with age. In the immunohistochemical study, the density of dopamine-beta-hydroxylase -positive axonal varicosities was measured in molecular, granule cell and p olymorphic layers of DG. The density in the polymorphic layer significantly decreased in the earlier stage of ageing (7-19 months), whilst the density in the molecular and granule cell layers decreased in the later stage (27 months). These findings suggested that a layer-specific decline occurred wi th age in the noradrenergic axon terminals in DG.