Feedback regulation of cholinergic modulation and hippocampal memory function

Acetylcholine may set the appropriate dynamics for learning within cortical structures, while removal of this modulatory influence may set the appropriate dynamics for recall. Here we use a combination of computational modeling and brain slice physiology to explore the role of cholinergic modulation in the hippocampal formation. A computational model of the feedback regulation of cholinergic modulation in hippocampal region CAI was developed, with an emphasis on the putative heteroassociative memory function of the Schaffer collaterals projecting from region CA3 to region CAI. Feedback regulation of cholinergic modulation in the model allowed the network to respond to novel patterns with strong cholinergic modulation, allowing accurate learning, and to respond to familiar patterns with a decrease in cholinergic modulation, allowing recall. This function required differences in the suppression of synaptic transmission at CAI synapses arising from region CA3, when compared to CAI synapses arising from the entorhinal cortex. Experiments in brain slice preparations of the hippocampal formation confirmed this prediction of the model.