Authors :
Presenting Author: Brittney Boublil, PhD – University of California, Irvine
Gergely Tarcsay, MS – University of California, Irvine
Justin Yi, BS – University of California, Irvine
Laura Ewell, PhD – University of California, Irvine
Rationale:
Early work on seizure generation and temporal lobe epilepsy (TLE) focused on the hippocampus, particularly the CA3 subregion, for its unique anatomy. CA3 has both strong recurrent (i.e., auto-associative) connections, where neurons receive input from their own axons, as well as commissural connections, where CA3 receives input from the contralateral CA3. Despite its unique anatomy and potential in seizure generation, little is known about CA3 function in epilepsy. Methods:
To investigate the impact of TLE on CA3 hippocampal function, we used a mouse model of focal TLE, in which mice were injected with kainic acid supra-hippocampally. We trained saline control (N = 6) and epileptic (N = 10) mice to forage in an open field while we performed high density, single-unit recordings from hippocampal CA1 and CA3, ipsilateral to the injection. We categorized cells as place or non-place cells using their spatial information score and a minimum peak firing rate of 2 Hz. Results:
In hippocampal CA1, we observed a decrease in peak firing rate (p = 0.02), more dispersed firing in space (p = 0.007), and decreased spatial coherence (p = 0.00001) of place cells in epileptic mice compared to saline controls. Interestingly, we did not observe these changes in CA3 despite significant anatomical changes in hippocampus, including massive reorganization of the dentate gyrus, which provides input to CA3. Conclusions:
We hypothesize that intact place coding in CA3 place cells in epileptic mice may be due to contralateral CA3 projections playing a compensatory role in epilepsy. Current analyses are underway to assess additional features of spatial coding, such as remapping and place field development with experience in novel environments. By better understanding hippocampal subnetwork dynamics and how they change with epilepsy we can gain insight into impaired memory processing in epilepsy.
Funding: This work was funded by NIH R01 1R01NS128222-01 to L.A.E., American Epilepsy Society Grant 835029 to L.A.E.