Abstracts

Rationale: Reproductive endocrine comorbidities are commonly observed in patients with temporal lobe epilepsy (TLE). Gonadotropin-releasing hormone (GnRH) neurons are the final common output in the neural regulation of hypothalamic-pituitary-gonadal axis function. We previously found that GnRH neuron firing and excitability are disrupted in the intrahippocampal kainic acid (IHKA) mouse model of TLE (1). GABA_A receptor activation is depolarizing in adult GnRH neurons (2). Here, we examined if GABA transmission to GnRH neurons is altered in IHKA mice and whether observed changes are dependent on ionotropic glutamate receptor (iGluR) signaling.

Methods: Adult female GnRH-tdTomato mice on the C57BL/6J background were injected with either KA (50 nl of 20 mM) or saline in the right dorsal hippocampus on diestrus. At 2 mo post-injection, 300-μm coronal brain slices were prepared on diestrus. Whole-cell voltage-clamp recordings of GABAergic spontaneous postsynaptic currents (sPSCs) were made between 1200-1600 h (1900 h lights off). Recordings targeted 49 tdTomato-expressing GnRH neurons in the medial septum (MS) or preoptic area (POA) with iGluR signaling either intact or blocked by kynurenic acid (1). Estrous cycle data from 1-month post-injection onward were analyzed to categorize each mouse with a regular cycle (4-6 d cycle period, “KA-regular”) or a long/disrupted cycle (> 7 d, “KA-long”) (1).

Results: With iGluR signaling intact, GABA sPSC frequency was significantly increased in POA GnRH neurons from the KA-long group (n = 4 cells, 3 mice) compared with both KA-regular (n = 3 cells, 2 mice) and saline-injected controls (n = 3 cells, 3 mice) (p < 0.01 for both comparisons). iGluR antagonism blocked this increase (p = 0.55, n=3-4 cells, 2-3 mice/group). sPSC frequency in MS GnRH neurons was not different between groups in either iGluR intact (n = 4 cells, 3-4 mice/group) or blocked conditions (n = 5-7 cells, 4-5 mice/group) (p >