Acetylcholine bidirectionally regulates learning and memory

Acetylcholine (ACh) is one of the most important neurotransmitters in the central cholinergic system; it specifically binds to muscarinic and nicotinic receptors and is degraded by acetylcholinesterase (AChE). ACh plays a crucial role in learning and memory. It is generally believed that, in the central nervous system, ACh promotes the conduction of brain nerves and accelerates information transmission. Besides, increasing central ACh levels can enhance memory ability and comprehensively improve brain function. Thus, AChE inhibitors (AChEI), which inhibit the degradation of ACh by AChE, have been used to treat Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). However, recent studies have shown that excessive ACh in the central nervous system impairs learning and memory. Here we review the roles of ACh in learning and memory; we focus on the adverse effects of excessive ACh, the possible mechanisms, and the bidirectional role of ACh in the pathology and cure of AD and PDD. We conclude that the timing and dose of ACh administration should be carefully prescreened when using it to alleviate learning and memory in dementia patients.