Biphasic effects of the cholinergic agonist carbachol on long-term potentiation in the dentate gyrus of the mammalian hippocampus

The dentate gyrus, an integral part of the hippocampal circuit, is capable of producing new neurons in adulthood, some of which become integrated into neuronal circuits that participate in processes underlying learning and memory. Acetylcholine (Ach) is an important neuromodulator of synaptic activity in the hippocampus but its action on activity-dependent plasticity of mature and young neurons has not been studied. Using standard hippocampal slice preparations and a functional assay for distinguishing young and mature neuronal populations, we found that Ach has a preferential stimulatory effect on long-term synaptic plasticity of mature neurons. This is in contrast to its inhibitory effect on synaptic plasticity of immature, adult-born neurons. This differential effect of Ach may contribute to differences in learning and memory in young and old brains, particularly in tasks that are sensitive to adult neurogenesis.