Abstracts

Rationale: The UP-DOWN state (UDS) pattern occurs during sleep and anesthesia when the flow of afferent signals to the brain decreases. The electrographic pattern generated in these conditions is mostly determined by the properties of internal connections of brain areas and it may reflect a strong or weak balance between excitatory and inhibitory networks. The goal of these experiments is to investigate whether organizational changes that exist in the epileptic brain are reflected in the pattern of the UDS. Methods: Naive and epileptic mice and rats were used in these experiments. Status Epilepticus (SE) was induced with pilocarpine hydrochloride injection. Field potentials were recorded with chronically implanted microelectrodes and single unit activity was recorded with glass microelectrodes. Recorded neurons were labeled by neurobiotine and identified later as granular cells or interneurons in histological sections. The following parameters of the UP-Down State were analyzed and compared between different groups of animals. 1) The frequency of BGA; 2) The duration of UP and Down phases; 3) Excitability changes after termination of the UP phase; 4) The existence of UP-spikes; 5) Temporal relation between areas generating UP-spikes. 6) Temporal relation between neuronal discharges and field potentials. Statistical analysis was performed using Prizm 4 (GraphPad, San Diego, CA). Results: We did not find any difference in the frequency of BGA between normal and epileptic mice. The differences between these two groups were observed in the following parameters of the UDS pattern. In epileptic animals: a) The duration of both the UP and Down phases is significantly longer; b) Recovery of network excitability after termination of the UP phase is longer. c) UP-spikes occur during the UP phase, which transiently interrupt the development of the normal electrographic pattern of UP phase. Our findings suggest that UP-spikes result from gigantic EPSPs generated in response to afferent activity. UP-spikes in different brain areas occur in close temporal relationship indicating the existence of pathological functional connections between these areas. Conclusions: Our data show that several parameters of the UDS are different in normal and epileptic brain. Changes in the duration of the UP- and Down phases as well increased time of recovery of excitability of epileptic brain after termination of UP phase could reflect alterations in the homeostatic properties of the neuronal network in epileptic brain. The existence of UP-spikes in epileptic brain is an additional electrographic pattern indicating epileptogenicity. They could be mediated by a network of epileptogenic pathologically interconnected neuronal clusters (PIN-clusters) postulated to be responsible for the occurrence and propagation of epileptiform activity between brain areas.