Abstracts

Impaired CA3 Dynamics in a Rodent Model of Temporal Lobe Epilepsy

Abstract number : 2.057
Submission category : 3. Neurophysiology / 3F. Animal Studies
Year : 2022
Submission ID : 2204551
Source : www.aesnet.org
Presentation date : 12/4/2022 12:00:00 PM
Published date : Nov 22, 2022, 05:25 AM

Authors :
Brittney Boublil, PhD – University of California Irvine; Gergely Tarcsay, MS – University of California Irvine; Laura Ewell, PhD – University of California - Irvine

Rationale: In epilepsy, hippocampal CA3 is thought to be critically involved in seizure generation because of the strong recurrence there. Despite this, little is understood about how CA3 function may be altered in epilepsy.

Methods: First, to determine whether CA3 exhibits structural changes we performed a histological analysis on tissue from epileptic and control mice. Mice received stereotaxic suprahippocampal injections of kainic acid (KA) (n = 14, 8 females, 6 males) and were perfused 6 weeks later for histological analysis. To test how CA3 function may be altered by these changes, we performed high density single unit recordings in epileptic and saline control mice. Mice were trained to forage in two familiar environments, one black and one white, while tetrodes were slowly advanced towards the CA3 subregion. Once tetrodes reached their target, we recorded hippocampal neural activity while mice explored both familiar and novel environments.

Results: The area of CA3 tended to be smaller on the KA injected side compared to the contralateral side (mean ± SEM; KA, 0.53, ± 0.3 mm2; contra, 0.60, ± 0.3 mm2; paired t-test, p ≤ 0.14). The amount of mossy fiber input normalized to CA3 area tended to be smaller on the KA injected side (mean ratio ± SEM; KA, 0.35, ± 0.04; contra, 0.42, ± 0.01; paired t-test, p ≤ 0.15). Additionally, we observed extreme variation in the amount of mossy fiber input on the KA injected side with some animals having none. Such variation was only present on the KA injected side (F-test, p ≤0.001). Initial experiments show hyperexcitable CA3; nearly 100 % of  cells that were recorded had place fields in the black-white familiar environments compared to the 30-40% of CA3 cells that are active in control animals. 

Conclusions: Together these results indicate that CA3 undergoes subtle structural changes and in some cases loses input from the dentate gyrus. Initial experiments suggest that these changes are associated with a hyperexcitable CA3. Further analyses are underway to determine whether CA3 place field size and stability are altered in familiar environments and to determine dynamics of remapping in novel environments. By better understanding CA3 dynamics and how they change with epilepsy we can gain insight into impaired memory processing in epilepsy.

Funding: : American Epilepsy Society (AES): Laura A. Ewell 835029; HHS, NIH, National Institute of Neurological Disorders and Stroke (NINDS): Brittney L Boublil T32 NS-45540
Neurophysiology