Computational model of carbachol-induced delta, theta, and gamma oscillations in the hippocampus

Field potential recordings from the rat hippocampus in vivo contain distinct frequency bands of activity, including δ (0.5-2 Hz), θ (4-12 Hz), and γ (30-80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the δ (CCH-δ), θ (CCH-θ), and γ (CCH-γ) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-θ, synchronous CCH-δ, and synchronous CCH-θ with increasing CCH concentration (Fellous and Sejnowski, Hippocampus 2000;10:187-197). In a network model of area CA3, the time scale for CCH-δ corresponded to the decay constant of the gating variable of the calcium-dependent potassium (K-AHP) current, that of CCH-θ to an intrinsic subthreshold membrane potential oscillation of the pyramidal cells, and that of CCH-γ to the decay constant of GABAergic inhibitory synaptic potentials onto the pyramidal cells. In model simulations, the known physiological effects of carbachol on the muscarinic and K-AHP currents, and on the strengths of excitatory postsynaptic potentials, reproduced transitions from asynchronous CCH-θ to CCH-δ and from CCH-δ to synchronous CCH-θ. The simulations also exhibited the interspersed CCH-γ/CCH-δ and CCH-γ/CCH-θ that were observed in experiments. The model, in addition, predicted an oscillatory state with all three frequency bands present, which has not yet been observed experimentally.