Sex and Estrous Cycle Stage Shape Left-Right Asymmetry in Chronic Hippocampal Seizures in Mice

Cathryn A. Cutia, Leanna K. Leverton, Catherine A. Christian-Hinman

Research output: Contribution to journalArticlepeer-review


Lateralization of hippocampal function is indicated by varied outcomes of patients with neurologic disorders that selectively affect one hemisphere of this structure, such as temporal lobe epilepsy (TLE). The intrahippo-campal kainic acid (IHKA) injection model of TLE allows for targeted damage to the left or right hippocampus, enabling systematic comparison of effects of left-right asymmetry on seizure and nonseizure outcomes. Although varying nonseizure phenotypic outcomes based on injection side in dorsal hippocampus were re-cently evaluated in this model, differences in chronic seizure patterns in left-(IHKA-L) versus right-injected (IHKA-R) IHKA animals have yet to be evaluated. Here, we assessed hippocampal seizure incidence in male and female IHKA-L and IHKA-R mice. Females displayed increased electrographic seizure activity compared with males at both two and four months postinjection. In addition, IHKA-L females showed higher seizure frequency than IHKA-R on diestrus and estrus at two months postinjection, but seizure duration and percent time in seizures were only higher in IHKA-L females on diestrus. These cycle stage-associated changes, however, did not persist to four months postinjection. Furthermore, this lateralized difference in seizure burden was not observed in males. These results indicate for the first time that the side of IHKA injection can shape chronic electrographic seizure burden. Overall, these results demonstrate a female-specific left-right asymmetry in hip-pocampal function can interact with estrous cycle stage to shape chronic seizures in mice with epilepsy, with implications for neural activity and behavior in both normal and disease states.

Original languageEnglish (US)
Article numberENEURO.0041-23.2023
Issue number6
StatePublished - Jun 2023


  • epilepsy
  • hippocampus
  • laterality
  • sex differences

ASJC Scopus subject areas

  • General Neuroscience


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