Sparsening and decorrelation of granule cell activity in the dentate gyrus by noradrenaline

The dentate gyrus in the hippocampus makes important contributions to the acquisition of episodic memories by transforming synaptic inputs from the entorhinal cortex into sparse and decorrelated activity patterns of its principal neurons, the granule cells. However, the underlying mechanism remains unclear. Using a combination of electrophysiological and optical recordings, together with optogenetic and pharmacological manipulations, we demonstrate that the release of noradrenaline plays a key role in this specialization via an enhancement of feedforward inhibition generated by cholecystokinin-expressing interneurons. By imposing coincidence detection with milliseconds temporal resolution onto granule cells, this enhancement of feedforward inhibition makes granule cell activity sparser and their firing patterns decorrelated. Since decorrelation contributes to efficient memory storage during auto-associative learning, these findings reveal a circuit mechanism by which an arousal signal facilitates memory formation in the hippocampus.