Rhythmic constraints on hippocampal processing: State and phase-related fluctuations of synaptic excitability during theta and the slow oscillation

Coordinated patterns of state-dependent synchronized oscillatory activity have been suggested to play differential roles in both the encoding and consolidation phases of hippocampal-dependent memories. Previous studies have concentrated on the mutually exclusive patterns of theta and sharp-wave/ripple activity because these were thought to be the only collective oscillatory patterns expressed in the hippocampus. Recently we (and others) have described a novel rhythmic activity expressed during anesthesia and deep sleep, the hippocampal slow oscillation (SO). In an attempt to describe the differential effects of theta and the SO on processing in the hippocampal circuit, we performed evoked potential analysis of two major pathways (the commissural and perforant) in urethan-anesthetized rats across spontaneously expressed theta and SO states. We show that synaptic excitability was significantly enhanced in all pathways during the SO as compared with theta with the exception of the medial perforant path to the dentate gyrus, which showed greater excitability during theta. Furthermore, within each ongoing rhythm, there was a phase-dependent modulation of synaptic excitability. This occurred across all sites and similarly favored the falling phase (positive to negative) of both theta and the SO. Differential effects on the input, processing, and output circuitries of the hippocampus across mutually exclusive coordinated oscillatory patterns expressed during different states may be relevant for the staging of memory processes in the medial temporal lobe.