Supplementary Figure 10: Capturing cells that encode position (P), head direction (H) or speed (S) in medial entorhinal cortex using an LN model framework.

The majority of cells classified as grid, head direction, or speed cells according to shuffled criteria were found to significantly encode either P, H, or S, respectively, using the LN model. Furthermore, the percentage of each MEC cell type captured by both methods did not differ between iWT and iCre-KO mice (P encoding: grid cells in iWT n = 33/37, iCre-KO 60/62, Z = −1.53, p = 0.13; border cells in iWT = 77/86, iCre-KO = 66/71, Z = −0.75, p = 0.45; H encoding: head direction cells in iWT = 208/225, iCre-KO = 229/240, Z = −1.35, p = 0.18; S encoding: speed cells in iWT = 52/69, iCre-KO = 69/89, Z = −0.32, p = 0.75; all two-tailed binomial tests). (a-b) Response profiles for cells that significantly encode position (a) and speed (b). Examples on the left show individual MEC cells that were classified as a grid, border (a, two leftmost examples) or speed (b, two leftmost examples) cell using the shuffled criterion. Examples on the right show cells that significantly encode position (a) or speed (b) but have tuning curve shapes that, while unconventional, still carry significant information regarding the position or running speed of the animal. Note that response profiles are model derived but qualitatively similar to tuning curves and plotted using similar units and were computed as in Hardcastle et al., 2017⁷. (c) Histogram illustrating the fraction of neurons identified as significantly encoding one or more variable using the LN model approach (PHS: iWT = 33.4%, iCre-KO = 36.2%, PH: iWT = 32.1%, iCre-KO = 35.3%, PS: iWT = 8.7%, iCre-KO = 7.3%, HS: iWT = 0.2%, iCre-KO = 0.2%, P: iWT = 13.9%, iCre-KO = 11.8%, H: iWT = 0.2%, iCre-KO = 0.2%, S: iWT = 0.8%, iCre-KO = 0.3%). Similar to what was reported in Hardcastle et al., 2017⁷, a large portion of superficial MEC neurons encode more than one navigational variable (exhibit mixed-selectivity) and, as a population, MEC neurons tend to encode position at a higher frequency than head direction or speed. (d) Boxplots of model fit for cells that significantly encoded one or more variables. Boxplots indicate the first and third quartiles by a box, and the median by a solid black line. Whiskers indicate the range, except for data falling above the third quartile or below the first quartile by at least 1.5 times the interquartile range. Outliers are indicated by plus symbols. In essence, model fit indicates how well the spiking of a single-cell can be predicted by the variable, or set of variables, of interest (e.g. position or position and head direction). We did not find any significant differences in model fit for any cell-type (Model fit mean ± SD: PHS iWT = 0.34 ± 0.34, n = 176, iCre-KO = 0.31 ± 0.32, n = 217, two-tailed WRS Z = 0.51, p = 0.61; PS iWT = 0.30 ± 0.30, n = 169, iCre-KO = 0.31 ± 0.31, n = 212, two-tailed WRS Z = 0.29, p = 0.77; PHS iWT = 0.12 ± 0.13, n = 46, iCre-KO = 0.13 ± 0.13, n = 44, Z = −0.38, p = 0.70; P iWT = 0.10 ± 0.13, n = 73, iCre-KO = 0.083 ± 0.096, n = 71, Z = 0.31, p = 0.76; H iWT = 0.043 ± 0.027, n = 5, iCre-KO = 0.41 ± 0.55, n = 4, t(7) = −1.55, p = 0.17; S iWT = 0.050 ± 0.049, n = 4, iCre-KO = 0.023 ± 0.010, n = 2, t(4) = 0.72, p = 0.51). Boxplots are not shown for HS cells, as the LN model detected significant HS encoding in one 1 iWT and 1 iCre-KO neuron (Model fit iWT = 0.018, iCre-KO = 0.020). (e) The majority of grid cells identified using shuffled criterion also significantly encoded P but a few (n = 4 iWT grid cells and 2 iCre-KO grid cells) only passed based on the shuffled criterion. Even so, we found a significant increase in spacing in iCre-KO mice when only considering the grid cells that passed the shuffled criterion and significantly encoded position (mean ± SD; iWT = 37.24 ± 9.30 cm, iCre-KO = 42.31 ± 10.67 cm, two-tailed WRS Z = −2.45, p = 0.014; n = 33 iWT grid cells and 60 iCre-KO grid cells).

7. Hardcastle, K., Maheswaranathan, N., Ganguli, S. & Giocomo, L.M. A multiplexed, heterogeneous, and adaptive code for navigation in medial entorhinal cortex. Neuron 94, 375–387 (2017).