Figure 2.

Transient depolarizing shifts in postsynaptic GABAergic signaling are a general feature of epileptiform activity. A, The postsynaptic response to GABA_AR activation was investigated in three in vitro models of epileptiform activity: (1) a 0 Mg²⁺ model (left); (2) a 4-AP model (middle); and (3) a spontaneous model (right). Gramicidin perforated patch-clamp recordings in current-clamp mode were made from CA3 pyramidal neurons, and GABA_AR-mediated responses were elicited every 10 s by delivering a puff of GABA (100 μm) to the cell soma. When individual responses to GABA could be clearly identified on the background activity, the effect on the membrane potential was calculated and defined as the GABA-mediated potential (blue circles). Note how GABA-mediated potentials became depolarizing during all three models of epileptiform activity. B, Representative GABA-mediated potentials corresponding to the dashed boxes in A. In many cases, the depolarizing effect of the GABA puff was sufficient to generate action potentials. C, Population data demonstrate that GABA_AR activation had a pronounced depolarizing effect on the membrane potential during the AD phase (***p < 0.001, paired t test).