Fig. 3: Ketamine acutely affects firing rates and disrupts single cell spatial scores.

a Firing rate averaged over neurons before (5 min) and after (10 min) control (magenta) or ketamine (green) injection. Solid line indicates mean and shaded regions show SEM (n = 3233 cells, mouse n = 8). Gray line at 0 indicates injection time. b Boxplot of mean change in firing rate for the 5 min before versus after the control (magenta) or ketamine (green) injection divided by the baseline firing rate. Central mark indicates the median, bottom and top edges of the box indicate the 25th and 75th percentiles, respectively, and whiskers extend to the most extreme data points not considered outliers. The mean firing rate of neurons changed significantly in the 5 min after ketamine injection compared to the 5 min after control injection (two-sided Wilcoxon matched pairs signed rank test, Z = −16.45, p < 10⁻¹⁰, n = 3233 neurons). c Change in the firing rate 60 min after ketamine injection from the mean firing rate 5 min prior to the injection. d Change in firing rate across 290 trials from the mean firing rate in the baseline epoch (trial 1–50). Note that due to variable changes in the running speed of individual mice, effects observed over trials (d) versus time elapsed (c) do not perfectly align. For (c, d), thin black lines are individual mice averaged across sessions (n = 8 mice); thick red line is mean firing rate across all neurons; shaded region shows SEM (n = 3233 cells). e Same as (a), for excitatory neurons (n = 2894 cells, mouse n = 8). f Same as (a), for inhibitory neurons (n = 339 cells, mouse n = 8). g Violin plot of the change in the mean firing rate between 5 min before and 5 min after an injection divided by the baseline firing rate of excitatory and inhibitory neurons. Excitatory and inhibitory neurons significantly increase their firing rate (two-sided Wilcoxon matched pairs signed rank test, excitatory: Z = 17.57, p < 10⁻¹⁰, n = 2894 cells; inhibitory: Z = 3.6, p = 0.0003, n = 339 cells). All violins have the same area, but the width represents the kernel probability density of the data at different values. Central mark of the boxplot indicates the median, bottom and top edges of the box indicate the 25th and 75th percentiles, respectively, and whiskers extend to the most extreme data points not considered outliers. h Single example of an MEC spatial cell. Left: Raster plot. Middle: Spatial firing rate map (color coded as in Fig. 1e). Right: Mean running speed per trial. i Left: Crest factor for the example cell shown in (h). Right: The average crest factor for all cells. j Left: Spatial information score for the example cell shown in (h). Right: The average spatial information score for all cells. k Average spatial stability values. For i-k, solid lines represent mean and shaded regions represent SEM. Control epoch is highlighted in magenta (trials 51–100). Ketamine epoch is highlighted in green (trials 101–300). N = 300 trials, 3233 cells, 8 mice. l Mean stability of neurons 30 min after baseline (black), control (magenta) and ketamine (green) injection. Line is mean and shaded region is SEM. m Comparison of the mean stability of neurons in the baseline (black), control (magenta), and ketamine (green) epochs. Data plotted as violin plots, as in (g). Spatial stability slightly differed between the baseline and the control epochs (Z = 2.93, p = 0.003). The spatial stability of neurons in the ketamine epoch (n = 50 trials post ketamine injection) was smaller than in the baseline epoch (Z = −18.12, p < 10⁻²⁰) and control epoch (Z = −17.69, p < 10⁻²⁰). Two-sided Wilcoxon matched pairs signed rank test, n = 3233 cells. Significant comparisons highlighted **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source data file.