Changes in hippocampal excitatory synaptic transmission during cholinergically induced theta and slow oscillation...

Neural processing in the hippocampus (HPC) during sleep is important for declarative memory storage. Previously, we have shown that alternations of sleep-like REM and non-REM brain states that involve changing patterns of synchronized oscillatory network activity in the HPC [i.e., theta and the slow oscillation (SO), respectively] robustly and differentially influence excitatory synaptic transmission in a variety of hippocampal pathways. Given that state in the HPC is dependent on variations in cholinergic tone in both sleep and under urethane anesthesia, in the present study we induced theta and SO states via systemic cholinergic manipulations in urethane-anesthetized rats to confirm similar changes in synaptic responsiveness. This was conducted using linear multiprobe recordings and current source density analysis of electrically evoked potentials in commissural and temporal ammonic inputs to CA1 and medial and lateral perforant path inputs to dentate gyrus (DG). Cholinergic agonism and antagonism induced theta and the SO, respectively, and similarly to the case with spontaneous states, also diminished and promoted, respectively, excitatory synaptic currents in all pathways (except for the medial perforant path input to DG which showed the opposite modulation). These results suggest that both state and cholinergic tone bias the hippocampal network during natural sleep across REM and non-REM episodes and that this modulation may play an important role in the consolidation of declarative memories.