This ratio is derived from input maps in which synaptic points were plotted for the different cell types (Figures 3A and 3B). We calculated

the mean composite synaptic amplitude (sum of photoactivation-induced synaptic current amplitudes divided by number of points from which a synaptic response was detected), from each layer for each cell and FG-4592 cell line then compared these values between cell types. We could not detect significant differences between L2Ps and L2Ss for the strength of input from either the deep or superficial layers (Figure 3E; superficial: 36.18 ± 2.5 pA for L2Ss [n = 15] versus 33.46 ± 2.5 pA for L2Ps [n = 11], p > 0.05, Mann-Whitney U test; deep: 22.06 ± 4.35 pA for L2Ss [n = 15] versus 27.38 ± 1.47 pA for L2Ps [n = 11], p > 0.05, Mann-Whitney U test). We therefore decided to base our microcircuit analysis on a digital readout of synaptic inputs (Figures 3A and 3B), thereby reducing the variability introduced by the analog readout via probabilistic synaptic transmission. As shown in Figures 3A to 3D, there are differences in the relative amount of deep to

superficial and superficial to superficial connections for L2Ss and the L2Ps. For each cell, we also calculated the percentage of synaptic points in the different layers as a fraction of the total number of synaptic points. Among the L2S population, on average, 83.55 ± 5.30% of all synaptic points arise from the superficial layers while only 16.45 ± 5.30% arise from the deep layers (n = 15). For L2Ps, 67.7 ± 5.51% of synaptic points are from the superficial layers Epacadostat solubility dmso and 32.3 ± 5.51% from deep layers (n = 11; Figure 3F). Comparing deep and superficial inputs within cell types, both L2Ss and L2Ps receive significantly more input from the superficial layers than from the deep layers (Figure 3F; L2P superficial versus deep: p < 0.05; L3P superficial versus deep: p < 0.05; Mann-Whitney U test). Comparing superficial inputs between cell types, L2Ss receive significantly more superficial input than L2Ps (Figure 3F;

p < 0.05, Mann-Whitney U test). In contrast, L2Ps receive significantly more deep layer input than L2Ss (Figure 3F; p < 0.05, Mann-Whitney U test). In fact, 7 out of 15 (46.67%) L2Ss received less than 5% of their total synaptic input from the deep layers, whereas every (11 out of 11) L2P received MYO10 more than 10% of their inputs from the deep layers. Microcircuit properties can be cell-type-specific or layer-specific (Schubert et al., 2007). In the MEC, we can differentiate between the microcircuit organization of different cell types in the same layer (pyramidal and stellate cells in layer 2) and the same cell type in different layers (pyramidal cells in layer 2 and 3). To analyze the spatial organization of the deep to superficial microcircuitry, we aligned the input maps to the main axis of the cell. The main axis was constructed as a perisomatic axis perpendicular to the pial surface (Figures 4A–4C).