Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice

Epilepsy-associated increase in gonadotropin-releasing hormone neuron firing in diestrous female mice is independent of chronic seizure burden severity

“…A limitation of the present study is that seizures were only recorded ipsilateral to the site of KA injection in the right dorsal hippocampus. Although seizures in the IHKA model primarily arise in the ipsilateral hippocampal region and many epileptiform events stay focally confined to the hippocampus (Lévesque and Avoli, 2013;Twele et al, 2017), seizure activity can spread and generalize to other brain regions (Sheybani et al, 2018), in some cases producing convulsive seizures (Bui et al, 2018;Lisgaras and Scharfman, 2022;Zeidler et al, 2018). However, other rodent models of TLE with primarily focal seizures also show prominent estrous cycle disruption (Amado et al, 1987;Christian et al, 2020;Edwards et al, 1999;Fawley et al, 2012;Scharfman et al, 2008).…”

“…Therefore, seizure generalization does not appear to be an absolute requirement for the development of comorbid reproductive endocrine dysfunction, but it remains to be determined whether there is a relationship between the rate of seizure generalization and downstream GnRH neuron and HPG axis dysfunction. Nevertheless, as both electrographic and convulsive seizure activity are consistently detected in the injected hippocampus in IHKA mice (Bouilleret et al, 1999;Lisgaras and Scharfman, 2022;Riban et al, 2002;Sheybani et al, 2018), depth EEG recording in the ipsilateral hippocampus as performed here enables recording of the vast majority of seizures in this model. Therefore, it is unlikely that the present results represent an underestimate of overall seizure burden in these mice.…”

Low-Cost Platform for Multianimal Chronic Local Field Potential Video Monitoring with Graphical User Interface (GUI) for Seizure Detection and Behavioral Scoring

“…To induce status epilepticus, we adopted the suprahippocampal KA model of chronic epilepsy ( Bedner et al, 2015 ). KA (Tocris) was dissolved in saline to provide a solution with a concentration of 20 m m and pH 7.4 ( Scharfman et al, 2000 ; Iyengar et al, 2015 ; Lisgaras and Scharfman, 2022 ). KA was injected suprahippocampally using a custom microinjection system ( B Zhu et al, 2019 ; MO-10, Narishige International).…”

“…Rodent studies of epilepsy often use longitudinal recordings to characterize disease progression and determine the efficacy of drug treatments ( Price et al, 2009 ; for review, see Simonato et al, 2014 ; Li et al, 2021 ; Lisgaras and Scharfman, 2022 ). In such experiments it is beneficial to simultaneously record video and electrophysiological signals such as electroencephalogram (EEG) or depth local field potential (LFP).…”

Increased GABA transmission to GnRH neurons after intrahippocampal kainic acid injection in mice is sex-specific and associated with estrous cycle disruption

“…To determine whether the epilepsy-associated changes in GnRH neuron firing activity in the IHKA model are associated with altered GABAergic transmission, we recorded GABAARmediated postsynaptic currents (PSCs) in GnRH neurons in slices of hypothalamus from IHKA mice and saline-injected controls. All recordings were performed at 2-3 months after injection, a time point by which a large majority of IHKA mice have been documented to display chronic spontaneous seizures (Cutia et al, 2022;Li et al, 2020;Lisgaras and Scharfman, 2022) and the majority of IHKA females exhibit disrupted estrous cycles (Cutia et al, 2022;Li et al, 2017). In light of the largely depolarizing effects of GABAAR activation in GnRH neurons, which could potentially promote increased firing activity, we recorded GABAergic transmission to GnRH neurons from males and diestrous females, as increased GnRH neuron firing was previously observed in IHKA mice from these groups (Li et al, 2018).…”