Although the sharpness and the stability of border fields show some increase from young to adult age, the basic properties of border cells HDAC inhibitor appear to be present from the outset. In particular, when a wall is inserted in parallel with the original peripheral firing field, the cells develop new firing fields along the insert, just as in adult rats. Head direction cells were also present from the outset. In contrast, grid cells, recorded in the same animals,

matured slowly, showing only minimal spatial periodicity during the first week of outbound exploration. The slow maturation of the grid cells and the fast expression of directional modulation confirm previous observations (Langston et al., 2010 and Wills et al., 2010). The presence of border cells in the immature MEC has implications for mechanisms of place cells. Place cells receive the majority of their cortical inputs from the entorhinal cortex (Witter and Amaral, 2004). Spatial signals are thought to originate primarily in the medial part of the entorhinal cortex (Fyhn et al., 2004, Hafting et al., 2005 and Hargreaves et al., 2005). The fact that the majority of hippocampus-projecting spatially modulated cells in this area are grid cells (Sargolini et al., Entinostat mw 2006 and Zhang et al., 2013) has raised the possibility that place cells emerge

by transformation of inputs from grid cells. One class of models relies on linear summation of impulses from cells with different grid spacing but similar grid phase and grid orientation (O’Keefe and Burgess, 2005, Fuhs and Touretzky, 2006, McNaughton et al., 2006 and Solstad et al., 2006). However, these models cannot readily account for the fact that place cells mature faster than grid cells in developing animals (Langston et al., 2010 and Wills et al., 2010), although with the addition of local circuit

mechanisms and Hebbian plasticity, second weakly modulated and irregular spatial inputs would in principle be sufficient to generate discrete and stable place fields (Rolls et al., 2006, de Almeida et al., 2009, Savelli and Knierim, 2010 and Monaco and Abbott, 2011). The present findings point to border cells as an alternative source of spatial information to the hippocampus of young animals, possibly with head direction cells as an additional source of modulation. Only a small fraction of the entorhinal cell population has properties defining them as border cells but retrograde labeling suggests that the hippocampal projections of these cells may be as dense as those of the more slowly developing grid cells (Zhang et al., 2013). The present study, in conjunction with the retrograde labeling study, suggests that these projections may be present from young age. Place cells may thus be formed by inputs from both grid cells and border cells but in the immature nervous system the border cells may provide the most reliable spatial inputs.