Abstracts

Rationale: During natural slow wave sleep (SWS) and conditions under anesthesia, alternating periods of neuronal activity (UP state) and relative quiescence (DOWN state) give rise to Slow Oscillations (<1Hz). During SWS in normal animals, physiological ripple oscillations in neocortex and hippocampus are associated with UP states. However, it is not clear if the occurrence of pathological High-Frequency Oscillations (pHFOs) in the epileptic brain, which are present during SWS, are also regulated by UP-DOWN state mechanisms. The goal of these experiments was to investigate whether pHFO in dentate gyrus (DG) occur during UP states or Down states or both under conditions of anesthesia. Methods: Experiments were carried out on normal and epileptic C57B6/J adult mice (20-30g) induced by pilocarpine injection (320mg/kg). Local field potentials and single unit recordings were performed under urethane anesthesia (1.25g/Kg) with supplemental doses of ketamine, xylazine and acepromazine as needed. Simultaneously, extracellular unit activity was recorded by a glass pipette (15-25MΩ) and local field potentials were recorded by 20-µm tungsten microelectrodes placed ≤500μm from the tip of the glass microelectrode. The depth position of the recording electrodes was calibrated by stimulus-evoked potentials in response to perforant path stimulation. Recorded neurons were identified by juxtacellular labeling methods. Electrophysiological data were analyzed using Datapac (Mission Viejo, CA) and MatLab software.Results: In normal and epileptic mice UP-DOWN states in DG were characterized by the occurrence of slow waves with a frequency between 0.3 and 0.5 Hz. Gamma activity (25-80Hz) was robust during UP states, but absent during DOWN states. However, in epileptic mice only we observed positive waves (duration ≈150ms) that contained pathological ripple (100-200Hz) and FR (200-500Hz) frequencies. In contrast to Gamma activity, pHFOs occurred preferentially during DOWN states, but pHFOs that occurred during UP states were accompanied typically by unit discharges. Conclusions: These data are consistent with our hypothesis that ripples in DG should be considered as a part of pathological electrographic events. It also suggests that pHFOs are generated by self-contained clusters of neurons, which are relatively independent of neocortical UP and DOWN state mechanisms. (Supported by NIH grant NS 02808, NS 33310)