Descarries_2005_J.Neural.Transm_112_149

To follow on prior studies of the cerebral cortex, we examined the acetylcholine innervation in the developing hippocampus of rat, by means of light and electron microscopic immunocytochemistry with a highly sensitive antibody against choline acetyltransferease. As in neocortex, the growth of this innervation mostly occurred within the first two weeks after birth. A preliminary ultrastructural survey indicated that a vast majority of these ChAT-immunostained axon varicosities were asynaptic during development as in the adult. In parallel, we quantified the cholinergic innervations of cerebral cortex and hippocampus in transgenic mice overexpressing human beta-amyloid peptide (hAPP(SW,IND)). A selective, widespread, plaque independent cholinergic denervation was thus demonstrated, first in hippocampus and then neocortex, in addition to a non-selective, plaque-dependent, local neurotoxic effect of aggregated beta-amyloid on ACh and 5-HT axons.