Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles

•Active neuronal populations inhibit non active neurons during memory formation•Optogenetic activation of GCs creates an artificial memory and abolishes natural recall•Non active neurons are excluded from the memory trace via lateral inhibition•Excitatory neurons activate SST+ interneurons and engage dendritic lateral inhibition

SummaryHippocampal neurons activated during encoding drive the recall of contextual fear memory. Little is known about how such ensembles emerge during acquisition and eventually form the cellular engram. Manipulating the activity of granule cells (GCs) of the dentate gyrus (DG), we reveal a mechanism of lateral inhibition that modulates the size of the cellular engram. GCs engage somatostatin-positive interneurons that inhibit the dendrites of surrounding GCs. Our findings reveal a microcircuit within the DG that controls the size of the cellular engram and the stability of contextual fear memory.