Axonal sprouting in commissurally projecting parvalbumin-expressing interneurons

Previous research has shown that in vivo on-demand optogenetic stimulation of inhibitory interneurons expressing parvalbumin (PV) is sufficient to suppress seizures in a mouse model of temporal lobe epilepsy (TLE). Surprisingly, this intervention was capable of suppressing seizures when PV-expressing interneurons were stimulated ipsilateral or contralateral to the presumed seizure focus, raising the possibility of commissural inhibition in TLE. There are mixed reports regarding commissural PV interneuron projections in the healthy hippocampus, and it was previously unknown whether these connections would be maintained or modified following the network reorganization associated with TLE. Using retrograde labeling and viral vector technology in both sexes and the intrahippocampal kainate mouse model of TLE, we therefore examined these issues. Our results reveal that healthy controls possess a population of commissurally projecting hippocampal PV interneurons. Two weeks post kainate injection, we observed a slight, but not statistically significant decrease in retrogradely labeled PV interneurons in the hippocampus contralateral to kainate and tracer injection. By 6 months post kainate, however, there was a significant increase in retrogradely labeled PV interneurons, suggesting commissural inhibitory axonal sprouting. Using viral green fluorescent protein expression selectively in PV neurons, we demonstrated sprouting of commissural PV projections in the dentate gyrus of the kainate-injected hippocampus 6 months post kainate. These findings indicate that PV interneurons supply direct inhibition to the contralateral hippocampus and undergo sprouting in a mouse model of TLE.