GABAA Receptor Activity Suppresses the Transition from Inter-ictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus
Yan-Yan Chang1• Xin-Wei Gong2• Hai-Qing Gong2• Pei-Ji Liang2• Pu-Ming Zhang2,*• Qin-Chi Lu1,*
1Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
2School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABAA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg2+-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABAA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABAA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
Epileptiform discharge,Gamma-aminobutyric acid,Bicuculline,Muscimol,Micro-electrode array,Hippocampal slice