Possible Mechanisms of the Complex Effects of Acetylcholine on Theta Activity, Learning, and Memory

Abstract

Disturbances of learning and memory are related to the impaired expression of rhythmic activity and phase synchronization in the hippocampus, entorhinal cortex, and other cortical areas. Several structures involved in the generation of the theta rhythm contain cholinergic cells and thus, acetylcholine concentration has to affect the parameters of the rhythm and play a substantial role in learning and memory. Here, we analyzed possible mechanisms of the effect of acetylcholine on the parameters of the theta rhythm in the hippocampus. The complex nature of these mechanisms is related to the effects of the cholinergic input from the medial septum to the hippocampus and the input from cholinergic cells of the pedunculopontine and oral pontine nuclei as well as of the Meynert nucleus on theta activity. Furthermore, the thalamic nucleus reu-niens, which also sends projections to the medial septum, hippocampal CA1 field, and entorhinal cortex, also affects theta activity. The supramamillary, posterior and medial mamillary nuclei of the hypothalamus also influence it via their interaction with the hippocampal formation and septum. Some structures involved in the generation of theta activity have long axon GABAergic cells, which exhibit inhibitory or disinhibitory effects on other structures. Acetylcholine, which contributes to increased excitation in the network involved in the generation of the theta rhythm, can lead to an increase in its expression or power, while the rhythm frequency is determined by inhibition and should increase when the inhibition is weakened.