Dentate gyrus interneurons modulate winner-take-all network dynamics in freely behaving mice.

The hippocampal dentate gyrus (DG) segregates input patterns aided by inhibitory circuits. Despite their importance, few studies have recorded identified DG interneurons in behaving animals. Here, we used electrophysiological recordings, bidirectional optogenetic manipulations, and modeling to characterize parvalbumin (PV)- and somatostatin (SST)-expressing interneurons in freely behaving mice. We employed machine learning to classify granule cells (GCs), mossy cells (MCs), and PV and SST interneurons simultaneously and studied their synaptic interactions in shaping spatial information and responses to entorhinal synaptic inputs. We demonstrated a central role for SST interneurons in regulating the impact of entorhinal excitation and for PV interneurons in feedback inhibition. Finally, optogenetic manipulations revealed a paradoxical observation: instead of merely suppressing firing in the surrounding network, DG interneuron stimulation exacerbated "winner-take-all" dynamics, including paradoxical polysynaptic excitation of some excitatory neurons. Such use-dependent modulation of winner-take-all dynamics may support the selection of content-bearing neuronal ensembles during cognitive processes.