How Good Vibes Turn Bad: Rise of Ictal Events From Oscillatory Network Activity. Focus on “Transient Depression of Excitatory Synapses on Interneurons Contributes to Epileptogenesis During Gamma Oscillations in the Mouse Hippocampal Slice”

Abstract

small alterations in network properties might destabilize the network. In the first, experimental, part of the study, Traub et al. used high concentrations (10 –100 M) of the metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) to evoke transitions from physiological to pathological oscillatory activity in the CA3 region of the hippocampus. Application of DHPG is known to be epileptogenic in vivo, and, under the in vitro conditions used in this study, DHPG resulted in oscillatory field potentials in the gamma range interspersed with epileptiform burst activity recordable from the CA3 pyramidal layer. In addition, very fast oscillations became apparent immediately before and during the bursts. Thus the DHPG-induced in vitro activity mimicked some of the defining features observed during the onset of ictal events in vivo. Subsequently, intracellular recordings showed that the transitions from gamma oscillations to burst activity were accompanied by an increase in excitatory input and a decrease in GABAergic input to CA3 pyramidal neurons. Conversely, the excitatory synaptic activity onto interneurons of the pyramidal layer sharply declined prior to the occurrence of a population burst, transiently weakening the interneuronal control of the pyramidal cells.