Abnormal UP/DOWN Membrane Potential Dynamics Coupled with the Neocortical Slow Oscillation in Dentate Granule Cells during the Latent Phase of Temporal Lobe Epilepsy123

The dentate gyrus, a major entry point to the hippocampus, gates (or filters) incoming information from the cortex. During sleep or anesthesia, the slow-wave oscillation (SWO) orchestrates hippocampus–neocortex communication, which is important for memory formation. The dentate gate is altered in temporal lobe epilepsy (TLE) early during epileptogenesis, which favors the propagation of pathological activities. Yet, whether the gating of physiological SWO by dentate granule cells (DGCs) is altered in TLE has remained unexplored. We combined intracellular recordings of membrane potential (V(m)) of DGCs and local field potential recordings of the SWO in parietal cortex in anesthetized rats early during epileptogenesis [post-status epilepticus (SE) rats]. As expected, in control rats, the V(m) of DGCs weakly and rarely oscillated in the SWO frequency range. In contrast, in post-SE rats, the V(m) of DGCs displayed strong and long-lasting SWO. In these cells, clear UP and DOWN states, in phase with the neocortical SWO, led to a bimodal V(m) distribution. In post-SE rats, the firing of DGCs was increased and more temporally modulated by the neocortical SWO. We conclude that UP/DOWN state dynamics dominate the V(m) of DGCs and firing early during epileptogenesis. This abnormally strong neocortical influence on the dynamics of DGCs may profoundly modify the hippocampus–neocortex dialogue during sleep and associated cognitive functions.