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Activation of γ-aminobutyric acid (GABA_A) receptors have been associated with the onset of epileptiform events. To investigate if a causal relationship exists between GABA_A receptor activation and ictal event onset, we activated inhibitory GABAergic networks in the superficial layer (2/3) of the somatosensory cortex during hyperexcitable conditions using optogenetic techniques in mice expressing channelrhodopsin-2 in all GABAergic interneurons. We found that a brief 30 ms light pulse reliably triggered either an interictal-like event (IIE) or ictal-like (“ictal”) event in the in vitro cortical 4-Aminopyridine (4-AP) slice model. The link between light pulse and epileptiform event onset was lost following blockade of GABA_A receptors with bicuculline methiodide. Additionally, recording the chronological sequence of events following a light pulse in a variety of configurations (whole-cell, gramicidin-perforated patch, and multi …