Actions and Interactions of Cholinergic and Excitatory Aminoacid Receptors on Phosphoinositide Signals, Excitotoxicity and Neuroplasticity

Abstract

The excitatory neurotransmitters acetylcholine and glutamate are involved in neuronal plasticity, which is thought to be an essential component of learning and memory. The loss of cognitive ability in Alzheimer’s disease and in age-associated memory impairment has been suggested to be secondary to a loss of central nervous system cholinergic transmission. Drugs which specifically disrupt cholinergic transmission have profound effects on learning and memory. A loss of cholinergic neurons clearly occurs early in the course of Alzheimer’s disease when memory loss is the only prominent symptom. In studies using experimental models of Alzheimer’s disease, lesioning cholinergic neurons also disrupts the ability of animals to learn. Glutamate has also been implicated in memory processes. Drugs that block glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor subtype, can produce cognitive deficits. An in vitro model of synaptic plasticity, long-term potentiation (LTP), is thought to be mediated in part through NMDA receptors. These studies suggest that both cholinergic and glutamatergic signals play an important role in memory processes and cognitive function.