PT - JOURNAL ARTICLE AU - Zachary Zeidler AU - Mikaela Brandt-Fontaine AU - Caara Leintz AU - Chris Krook-Magnuson AU - Tay Netoff AU - Esther Krook-Magnuson TI - Targeting the Mouse Ventral Hippocampus in the Intrahippocampal Kainic Acid Model of Temporal Lobe Epilepsy AID - 10.1523/ENEURO.0158-18.2018 DP - 2018 Jul 06 TA - eneuro PG - ENEURO.0158-18.2018 4099 - http://www.eneuro.org/content/early/2018/07/06/ENEURO.0158-18.2018.short 4100 - http://www.eneuro.org/content/early/2018/07/06/ENEURO.0158-18.2018.full AB - Here we describe a novel mouse model of temporal lobe epilepsy (TLE) that moves the site of kainate injection from the rodent dorsal hippocampus (corresponding to the human posterior hippocampus) to the ventral hippocampus (corresponding to the human anterior hippocampus). We compare the phenotypes of this new model – with respect to seizures, cognitive impairment, affective deficits, and histopathology – to the standard dorsal intrahippocampal kainate model. Our results demonstrate that histopathological measures of granule cell dispersion and mossy fiber sprouting maximize near the site of kainate injection. Somewhat surprisingly, both the dorsal and ventral models exhibit similar spatial memory impairments in addition to similar electrographic and behavioral seizure burdens. In contrast, we find a more pronounced affective (anhedonic) phenotype specifically in the ventral model. These results demonstrate that the ventral intrahippocampal kainic acid model recapitulates critical pathologies of the dorsal model while providing a means to further study affective phenotypes such as depression in TLE.Significance Statement Temporal lobe epilepsy (TLE) is characterized by spontaneous recurring seizures. TLE additionally features cognitive and affective comorbidities that impair quality of life. Animal models studying TLE are critical to advance our understanding of the disorder. A current popular model targets the dorsal hippocampus with a focal injection of kainic acid to induce epilepsy. Evidence suggest targeting the ventral hippocampus may produce a model of TLE with distinct benefits. We present data demonstrating that targeting the mouse ventral hippocampus with kainic acid creates a TLE model with similar seizure and cognitive phenotypes to the standard dorsal model but with additional, pronounced affective features, including anhedonia. These results describe a new tool for epilepsy researchers to better study comorbidities of TLE.