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 delta (0.5-2 Hz), theta (4-12 Hz), and gamma (30-80 Hz), that are correlated with the behavioral state of the animal. The cholinergic agonist carbachol (CCH) induces oscillations in the delta (CCH-delta), theta (CCH-theta), and gamma (CCH-gamma) frequency ranges in the hippocampal slice preparation, eliciting asynchronous CCH-theta, synchronous CCH-delta, and synchronous CCH-theta with increasing CCH concentration (Fellous and Seinowski, Hippocampus 2000;1 0:187-197). In a network model of area CA3, the time scale for CCH-delta corresponded to the decay constant of the gating variable of the calcium-dependent potassium (K-AHP) current, that of CCH-theta to an intrinsic subthreshold membrane potential oscillation of the pyramidal cells, and that of CCH-gamma 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-theta to CCH-delta and from CCH-delta to synchronous CCH-theta. The simulations also exhibited the interspersed CCH-gamma/CCH-delta and CCH-gamma/CCH-theta 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.