Are the Breaks Breaking Down?

Altered Hippocampal Interneuron Activity Precedes Ictal Onset Miri ML, Vinck M, Pant R, Cardin JA. Elife. 2018;7. pii: e40750. doi:10.7554/eLife.40750. Although failure of GABAergic inhibition is a commonly hypothesized mechanism underlying seizure disorders, the series of events that precipitates a rapid shift from healthy to ictal activity remains unclear. Furthermore, the diversity of inhibitory interneuron populations poses a challenge for understanding local circuit interactions during seizure initiation. Using a combined optogenetic and electrophysiological approach, we examined the activity of identified mouse hippocampal interneuron classes during chemoconvulsant seizure induction in vivo. Surprisingly, synaptic inhibition from parvalbumin-(PV) and somatostatin-expressing (SST) interneurons remained intact throughout the preictal period and early ictal phase. However, these 2 sources of inhibition exhibited cell type-specific differences in their preictal firing patterns and sensitivity to input. Our findings suggest that the onset of ictal activity is not associated with loss of firing by these interneurons or a failure of synaptic inhibition but is instead linked with disruptions of the respective roles these interneurons play in the hippocampal circuit.