Abstract
This chapter reviews a series of recent studies indicating that the grafts of acetylcholine-rich tissue into the brain of aged rats can influence age-dependent learning and memory deficits, perhaps by a cholinergic mechanism. In aged rats, significant cell loss has been reported in the pyramidal layer of the hippocampal formation, as well as a significant reduction in axodendritic and axosomatic synapses in the granular cell layer of the dentate gyrus. In addition, aged rats show a dramatic astrocytic hypertrophy, possibly indicative of an ongoing response to neuronal degeneration. Several reports show significant decrease in muscarinic binding sites, in acetylcholine synthesis, and in high-affinity choline uptake in the hippocampal formation. These cholinergic deficits are further supported by evidence that pyramidal cells of aged rats show a decrease in responsiveness to iontophoretically applied acetylcholine. Although no actual cell loss in the basal forebrain cholinergic system has been reported, a recent study has observed significant atrophy of these neurons in aged mice.
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