Reduction of Serotonergic Innervation in the Hippocampal Formation of Aged Tree Shrews

The serotonergic and cholinergic neurotransmitter systems interact during processes of learning and memory. Although the effects of aging on cholinergic innervation has been extensively investigated, it is not clear how the serotonergic innervation is altered during aging. The hippocampal formation, a target area of both cholinergic and serotonergic fibers, is a crucial structure for learning and memory processes. In this study, we used immunocytochemistry against serotonin to quantify the serotonergic innervation pattern in the hippocampal subfields of young (± 1 year) and aged (4–9 years) tree shrews (Tupaia belangeri). Our results revealed in aged tree shrews: i) a significantly decreased fiber density in the stratum radiatum of CA1 and CA3 and in the stratum oriens of CA3; and ii) a significantly lower optical density in the CA3 area and the inner one-third of the molecular layer of the DG. Similar, yet not statistically significant, results were observed for other hippocampal subfields. The results indicate that aging affects the serotonergic innervation of the hippocampal formation. Furthermore, it was apparent that the inter-individual differences in the serotonergic innervation of the hippocampal formation of young tree shrews was much higher than in aged animals, suggesting that a loss of plasticity is inevitable during aging.