MEC STELLATE CELLS SHAPE THE SPATIAL MAPS IN DG GRANULE CELLS

The dentate gyrus (DG) plays a key role in the emergence of spatial and contextual maps within the hippocampus during learning. Granule cells (GCs) of the DG receive their major cortical input from the medial entorhinal cortex layer II stellate cells (SCs) via the perforant path. To determine how SC inputs shape the formation and persistence of spatial representations by GC assemblies, and whether they contribute to the ability of the DG to differentiate between distinct environments, we chemogenetically modulated the activity of SCs. For this, we used two transgenic mouse lines to either de-(hM3Dq) or hyper-(hM4Di) polarize SC inputs to the DG. Using 2-photon in vivo calcium imaging, we captured GCs activity in head-fixed mice exploring familiar and novel virtual environments. Our results show that silencing of ~27% of SCs resulted in a mild reduction in the activity of GCs and in a subtle sparsification of spatial maps without changing their stability over time. In marked contrast, depolarization of an equivalent fraction of SCs resulted in the inactivation of the vast majority of GCs with place fields under control conditions. In parallel, few previously inactive GCs were progressively recruited as place cells and formed alternative but unique spatial maps for each environment. Behavioural tests in freely moving mice revealed that depolarizing SCs caused the inability to distinguish novel from familiar objects. Thus, excessive activity in SCs impairs novel object discrimination and results in a reversable loss of spatial information in the DG.