Abstracts

Rationale: Temporal lobe epilepsy is one of the most common types of epilepsy in adults and causes pervasive memory impairments which significantly impacts quality of life. In pilocarpine-treated epileptic mice, we have recently found desynchronization between the CA1 and dentate gyrus (DG) region of the hippocampus (HPC), such as reduced theta coherence and desynchronized interneuron firing between the CA1 and DG. The medial entorhinal cortex (MEC) is the upstream region sending direct spatial inputs into HPC, and is also affected in epilepsy. Thus, it remains unclear whether synchronization deficits in HPC reflect impaired inputs from MEC and when these deficits emerge following epileptogenesis. Cognitive processes require precise communication between circuits, suggesting that altered timing between HPC and MEC may contribute to epilepsy-associated cognitive deficits.

Methods: We have performed simultaneously in vivo electrophysiology with 512-channel silicon probes in HPC and MEC of epileptic and control mice running in virtual reality. We chose two time points (3 weeks post pilocarpine, 8 weeks post pilocarpine) to capture the early and late stages of epilepsy.

Results: Preliminary analysis using local field potential (LFP) power, multiunit activity, and coherence measures revealed that epileptic mice had altered synchronization between the MEC and HPC. Epileptic mice show reduced theta phase coherence between MEC and CA1, and reduced phase locking of MEC layer II spiking to CA1 (but not local) theta oscillations

Conclusions: Together, these data indicate a specific impairment in the timing of MEC inputs into HPC, which may contribute to the reduced coherence and altered spike timing we have previously found in epileptic mice. Future analysis will focus on single-unit analysis to determine whether excitatory and inhibitory neurons are specifically altered, and whether place coding in MEC shows impairments before CA1 in epileptic mice.

Funding: Please list any funding that was received in support of this abstract.: R01NS116357, CURE Taking Flight Award, AES Junior Investigator Award.