We investigate the effects of cellular-level cholinergic neuromodulation on the physiology of a realistic, anatomically reconstructed CA3 pyramidal cell model. The model has 385-compartments, contains a wide variety of ion channels (Na, KDR, KC, KA, KM, KAHP, CaL, CaN, CaT), calcium diffusion, buffering and pumping, and represents an updating of a model of Migliore et al. (J Neurophys 73:1157-1168, 1995) to reflect more recent biological data. The simulated application of acetylcholine resulted in several observed changes in single-cell physiology: 1) a transition from bursting ("complex-spiking") to regular spiking 2) an increased speed of action potential backpropagation 3) an increased amplitude of backpropagating action potentials and 4) a decrease in dendritic calcium influx. These results confirm some earlier studies of ours in a simpler pyramidal cell model and are consistent with the "two stage" memory model proposed by Buzsáki (Neuroscience 31:551-570, 1989). The implications for this model of hippocampal function as well as for Alzheimer's disease are discussed.

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