Spike afterpotentials shape the in-vivo burst activity of principal cells in medial entorhinal cortex

Principal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials, as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in MEC principal neurons. Next, we correlated the afterpotentials with the cells' propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their inter-spike intervals (ISIs) were typically between five and fifteen milliseconds. The ISI distributions of Layer-II cells without DAPs peaked sharply at around four milliseconds and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real two-dimensional arenas (Latuske et al., 2015). Apart from slight variations in grid spacing, no difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting and had no DAPs. As various mechanisms for modulating ion-channels underlying DAPs exist, our results suggest that temporal features of MEC activity can be altered while maintaining the cells' overall spatial tuning characteristics. Depolarizing afterpotentials (DAPs) are frequently observed in principal neurons from slice preparations of rodent medial entorhinal cortex (MEC), but their functional role is unknown. Analyzing whole-cell data from mice running on virtual tracks, we show that DAPs do occur during behavior. Cells with prominent DAPs are found in Layer II; their inter-spike intervals reflect DAP time-scales. In contrast, neither the rarely bursting cells in Layer III, nor the high-frequency bursters in Layer II, have a DAP. Extracellular recordings from mice exploring real two-dimensional arenas demonstrate that grid cells within these three groups have similar spatial coding properties. We conclude that DAPs shape the temporal response cha