Optogenetic techniques provide powerful tools for bidirectional control of 
neuronal activity and investigating alterations occurring in excitability 
disorders, such as epilepsy. In particular, the possibility to specifically 
activate by light-determined interneuron populations expressing 
channelrhodopsin-2 provides an unprecedented opportunity of exploring their 
contribution to physiological and pathological network activity. There are 
several subclasses of interneurons in cortical areas with different functional 
connectivity to the principal neurons (e.g., targeting their perisomatic or 
dendritic compartments). Therefore, one could optogenetically activate specific 
or a mixed population of interneurons and dissect their selective or concerted 
inhibitory action on principal cells. We chose to explore a conceptually novel 
strategy involving simultaneous activation of mixed populations of interneurons 
by optogenetics and study their impact on ongoing epileptiform activity in mouse 
acute hippocampal slices. Here we demonstrate that such approach results in a 
brief initial action potential discharge in CA3 pyramidal neurons, followed by 
prolonged suppression of ongoing epileptiform activity during light exposure. 
Such sequence of events was caused by massive light-induced release of GABA from 
ChR2-expressing interneurons. The inhibition of epileptiform activity was less 
pronounced if only parvalbumin- or somatostatin-expressing interneurons were 
activated by light. Our data suggest that global optogenetic activation of mixed 
interneuron populations is a more effective approach for development of novel 
therapeutic strategies for epilepsy, but the initial action potential generation 
in principal neurons needs to be taken in consideration.