The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory

Extensive evidence indicates that disruption of cholinergic function is characteristic of aging and Alzheimer's disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age-related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD. Recent research, however, suggests that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits and that age-related changes in cholinergic function typically occur within the context of changes in several other neuromodulatory systems. Evidence reviewed in this paper suggests that interactions between the cholinergic system and several of these neurotransmitters and neuromodulators--including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II--may be important in learning and memory. Thus, it is important to consider not only the independent contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between these systems to the learning and memory deficits associated with aging and AD.