Patterns of the UP-Down state in normal and epileptic mice

Goal of this manuscript is to investigate whether changes that exist in epileptic brain generating spontaneous seizures are reflected in the pattern of the UP-Down state (UDS) recorded from the neocortex and dentate gyrus. Experiments were carried out on naive and epileptic mice under urethane anesthesia. Local field potentials were recorded with chronically implanted microelectrodes and single unit activity was recorded with glass microelectrodes. Recorded neurons were labeled by neurobiotin and identified later as granular cells or interneurons in histological sections. The following major features differentiate the pattern of UDS in epilepsy from normal. (1) The duration of UP and Down phases is significantly longer. (2) Recovery of network excitability after termination of the UP phase is longer. (3) UP-spikes occur during the UP phase, which transiently interrupt the development of the normal electrographic pattern of UP phase. Our data provide evidence that UP-spikes result from gigantic EPSPs generated in response to afferent activity. UP-spikes in the neocortex and dentate gyrus occur in close temporal relationship indicating the existence of direct or indirect pathological functional connections between these areas. Changes in the duration of UP and Down phases as well increased time of recovery of excitability of epileptic brain after termination of UP phase suggest alterations in the homeostatic properties of neuronal network in epileptic brain. We suggest that the existence of UP-spikes in epileptic brain may be an additional electrographic pattern indicating epileptogenicity. Unraveling the neuronal substrates of UP-spikes may further improve our understanding of the mechanisms of epilepsy.