Intrinsic Mechanisms of Frequency Selectivity in the Proximal Dendrites of CA1 Pyramidal Neurons

Gammaoscillations are thought to play a role in learning and memory. Two distinct bands, slow (25-50 Hz) and fast (65-100 Hz) gamma, have been identified in area CA1 of the rodent hippocampus. Slow gamma is phase locked to activity in area CA3 and presumably driven by the Schaffer collaterals (SCs). We used a combination of computational modeling and in vitro electrophysiology in hippocampal slices of male rats to test whether CA1 neurons responded to SC stimulation selectively at slow gamma frequencies and to identify the mechanisms involved. Both approaches demonstrated that, in response to temporally precise input at SCs, CA1 pyramidal neurons fire preferentially in the slow gamma range regardless of whether the input is at fast or slow gamma frequencies, suggesting frequency selectivity in CA1 output with respect to CA3 input. In addition, phase locking, assessed by the vector strength, was more precise for slow gamma than fast gamma input. This frequency selectivity was greatly attenuated when the slow Ca2+-dependent K+ (SK) current was removed from the model or blocked in vitro with apamin. Perfusion of slices with BaCl2 to block A-type K+ channels tightened this frequency selectivity. Both the broad-spectrum cholinergic agonist carbachol and the muscarinic agonist oxotremorine-M greatly attenuated the selectivity. The more precise firing at slower frequencies persisted throughout all of the pharmacological manipulations conducted. We propose that these intrinsic mechanisms provide a means by which CA1 phase locks to CA3 at different gamma frequencies preferentially in vivo as physiological conditions change with behavioral demands.