GABA Receptor Activity Suppresses the Transition from Inter-ictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus / 神经科学通报·英文版

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg-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 Mg-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 GABA 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 GABA 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 GABA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.

Exploring spatiotemporal patterns of epileptiform discharge in hippocampal slice using multi-electrode arrays / 生理学报

To investigate the spatiotemporal properties of epileptiform activity in vitro, 400 microm-thick transverse hippocampal slices were prepared from juvenile rat and planar multi-electrode array (MEA) containing 60 electrodes was used to record the electrical activity induced by bath application of high potassium artificial cerebrospinal fluid (ACSF) on slices. Following successful induction of epileptiform bursts, phenobarbital sodium was applied to test for its inhibitory effects on bursting activity in different regions of slice. Region-specific characteristics of epileptiform activity and anticonvulsant actions of phenobarbital sodium in the hippocampal network were determined by comparing the population activity obtained from MEA. The results showed that: (1) 15 min after high-K+ ACSF application, rhythmic and synchronous epileptiform bursts could be detected from all CA sub-regions. Quantitative analysis indicates that the firing patterns of different CA sub-regions were not statistically different (P>0.05). However, no bursting activity was recorded from granular cells in dentate gyrus, only sparse spikes were observed, with frequency significantly lower than that in CA regions (P<0.05). (2) The high-K+-induced bursting activity could last for more than 40 min with stable bursting activities. (3) Bath application of 60 micromol/L phenobarbital sodium inhibited the bursting activities on hippocampal slice. Bursting activities in CA3c and CA1 were firstly suppressed. 10 min after the phenobarbital sodium application, strong bursting activities persisted only in some of pyramidal cells in CA3a and CA3b. These results show that MEA could be applied for studying the spatial and temporal properties of epileptiform activity in vitro, as well as the region-specific effects of anti-epileptic drugs.