UC Irvine

Tests were made for use-dependent plasticity in the cholinergic projections to hippocampus. Transient infusion of the cholinergic agonist carbachol into hippocampal slices induced rhythmic activity that persisted for hours after washout. Comparable effects were obtained with physostigmine, a drug that blocks acetylcholine breakdown and thereby enhances cholinergic transmission. It thus seems that activation of cholinergic synapses induces lasting changes in hippocampal physiology. Two lines of evidence indicated that cholinergic synapses are also the sites at which the plasticity is expressed. First, the induction and expression of the rhythms were not blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonovaleric acid, indicating that a long-term potentiation effect between pyramidal cells was not involved. Second, a muscarinic antagonist (atropine) completely abolished stable rhythmic activity after agonist washout. This result indicates that endogenous cholinergic activity is responsible for the persistence of rhythmic oscillations. These experiments suggest that short periods of intense cholinergic activity induce lasting changes in cholinergic synapses and thus extend such forms of plasticity to beyond the glutamatergic system.