TY - JOUR T1 - Dynamic and Sex-Specific Changes in Gonadotropin-Releasing Hormone Neuron Activity and Excitability in a Mouse Model of Temporal Lobe Epilepsy JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0273-18.2018 SP - ENEURO.0273-18.2018 AU - Jiang Li AU - Jordyn A. Robare AU - Liying Gao AU - M. Amin Ghane AU - Jodi A. Flaws AU - Mark E. Nelson AU - Catherine A. Christian Y1 - 2018/09/11 UR - http://www.eneuro.org/content/early/2018/09/12/ENEURO.0273-18.2018.abstract N2 - Reproductive endocrine disorders are prominent co-morbidities of temporal lobe epilepsy (TLE) in both men and women. The neural mechanisms underlying these co-morbidities remain unclear, but hypothalamic gonadotropin-releasing hormone (GnRH) neurons may be involved. Here we report the first direct demonstrations of aberrant GnRH neuron function in an animal model of epilepsy. Recordings of GnRH neuron firing and excitability were made in acute mouse brain slices prepared 2 months after intrahippocampal injection of kainate (KA) or control saline, a well-established TLE model in which most females develop co-morbid estrous cycle disruption. GnRH neurons from control females showed elevated firing and excitability on estrus compared with diestrus. By contrast, cells from KA-injected females that developed prolonged, disrupted estrous cycles (KA-long) showed the reverse pattern. Firing rates of cells from KA-injected females that maintained regular cycles (KA-regular) were not different from controls on diestrus, but were reduced on estrus. In KA-injected males, only GnRH neurons in the medial septum displayed elevated firing. In contrast to the diestrus-vs.-estrus and sex-specific changes in firing, GnRH neuron intrinsic excitability was elevated in all KA-injected groups, indicating a role for afferent synaptic and neuromodulatory inputs in shaping overall changes in firing activity. Furthermore, KA-injected females showed cycle-stage-specific changes in circulating sex steroids on diestrus and estrus that also differed between KA-long and KA-regular groups. Together, these findings reveal that the effects of epilepsy on the neural control of reproduction are dynamic across the estrous cycle, distinct in association with co-morbid estrous cycle disruption severity, and sex-specific.Significance Statement People with epilepsy are at higher risk of reproductive endocrine disorders compared with the general population, but the neural mechanisms linking epilepsy and these co-morbidities are unknown. Here we report changes in the function of gonadotropin-releasing hormone (GnRH) neurons, which control fertility, in a mouse model of temporal lobe epilepsy. GnRH neurons from epileptic female mice showed changes in activity dependent on estrous cycle stage and associated with severity of cycle disruption. The impacts of epilepsy on GnRH neurons in males were less severe. These findings provide novel evidence for impacts of epilepsy on GnRH neuron function, and will thus be of clinical relevance in developing new strategies to ameliorate reproductive co-morbidities and to treat the underlying seizures and epilepsy. ER -