GABAergic transmission facilitates ictogenesis and synchrony between 1 CA 3 , hilus , and dentate gyrus in slices from epileptic rats

31 32 The impact of regional hippocampal interactions and GABAergic transmission on ictogenesis 33 remain unclear. Cortico-hippocampal slices from pilocarpine-treated epileptic rats were compared to 34 controls to investigate associations between seizure-like events (SLE), GABAergic transmission, and 35 neuronal synchrony within and between cortico-hippocampal regions. Multielectrode array recordings 36 revealed more prevalent hippocampal SLE in epileptic tissue when excitatory transmission was 37 enhanced and GABAergic transmission was intact (0Mg) than when GABAergic transmission was 38 blocked (0Mg+BMI). When activity within individual regions was analyzed, spectral and temporal 39 slow oscillation/SLE correlations and cross-correlations were highest within the hilus of epileptic 40 tissue during SLE, but were similar in 0Mg and 0Mg+BMI. GABAergic facilitation of spectral “slow” 41 oscillation and ripple correlations was most prominent within CA3 of epileptic tissue during SLE. 42 When activity between regions was analyzed, slow oscillation and ripple coherence was highest 43 between the hilus and dentate gyrus as well as between the hilus and CA3 of epileptic tissue during 44 SLE, and was significantly higher in 0Mg than 0Mg+BMI. High 0Mg-induced SLE cross-correlations 45 between the hilus and dentate gyrus as well as between the hilus and CA3 were reduced or abolished in 46 0Mg+BMI. SLE cross-correlation lag measurements provided evidence for a monosynaptic connection 47 from the hilus to the dentate gyrus during SLE. Findings implicate the hilus as an oscillation generator, 48 whose impact on other cortico-hippocampal regions was mediated by GABAergic transmission. Data 49 also suggest that GABAA receptor-mediated transmission facilitated back-propagation from CA3/hilus 50 to the dentate gyrus and that this back-propagation augmented SLE in epileptic hippocampus. 51 52