Extended Data Fig. 2: Recording set up and tuning properties of mFC neurons in the ABCD task. | Nature

Extended Data Fig. 2: Recording set up and tuning properties of mFC neurons in the ABCD task.

From: A cellular basis for mapping behavioural structure

Extended Data Fig. 2

a) Coronal slice from an implanted mouse showing silicon probe track terminating in the prelimbic region of mFC. b) The laminar profile of probe channel positions for each mouse. Shanks A-F in Cambridge neurotech probes are arranged posterior-to-anterior. 90.7% of all recorded neurons were histologically localised in mFC regions based on the inferred channel position: 68.3% in Prelimbic cortex, 11.3% in Anterior Cingulate cortex, 6.1% in Infralimbic cortex and 5.0% in M2. Of the remaining 9.3%, 4.8% could not be localised to a specific peri-mFC region within the atlas coordinates as they were erroneously designated to peri-mFC white matter areas, likely due to variations between actual region boundaries and atlas derived ones, 2.2% were found in the dorsal peduncular nucleus, 1.1% in the striatum, 0.6% in the medial orbital cortex, 0.3% in the lateral septal nucleus and 0.3% in Olfactory cortex. c) Data was spike sorted across concatenated sessions spanning two recording days for the GLM analyses below and later anchoring analysis in Figs. 57. Top: Here we show an example “Estimated drift trace” for a concatenated double day, showing a largely stable recording set up. The plot shows the estimated probe drift relative to the brain across the two recording days along the depth of the neuropixels probe. Bottom: Example mean spike waveforms from 3 different neurons across 3 different animals. The plots show the mean of the first 100 spikes on day1 (black) and the mean of the last 100 spikes on day2 (red), illustrating stability of spike detection across days. The spikes are from neuron 1 and neuron 2 in Extended Data Fig. 6b and the neuron in Fig. 5e respectively. Scale bars: Vertical: 200 µV, Horizontal: 0.5 ms. d) Top: a schematic of the variables inputted into a generalised linear model that predicts neuronal activity across tasks and states. The model captured variance as a function of goal-progress, place, speed, acceleration, time from reward and distance from reward. Only data spike sorted across two days (6 unique tasks) was used to ensure this analysis is sufficiently powered. Bottom Left: A histogram showing the mean regression coefficient values for goal-progress as a regressor across task/state combinations for each neuron. One-sample T-test (two-sided) against 0: N = 1252 neurons; statistic=21.7; P = 8.93 × 10-89, df = 1251. Bottom right: A histogram showing the mean regression coefficient values for place as a regressor across task/state combinations for each neuron. One-sample T-test (two-sided) against 0: N = 1252 neurons; statistic=24.9; P = 3.31 × 10-111, df = 1251. e) Pie-charts showing the proportions of cells calculated using the results of the generalised linear model above in addition to cross-task correlations between tuning to goal-progress and place. Only data spike sorted across two days (6 unique tasks) was used to ensure this analysis is sufficiently powered. Plot shows proportions of neurons with i) significant regression coefficient values for goal-progress or place ii) Significantly positive cross-task correlation for goal-progress or place. It also shows proportions of state tuned neurons derived from a separate z-scoring analysis (More details in Methods under “Tuning to basic task variables”). Proportion of all neurons that are goal-progress cells: 74%; Two proportions test: N = 1252 neurons, z = 35.5, P = 0.0. Proportion of goal-progress neurons that are state tuned: 64% Two proportions test: N = 931 neurons, z = 26.8, P = 0.0. Proportion of neurons tuned to goal-progress and state that are also tuned to place: 63%, Two proportions test: N = 597 neurons, z = 21.2, P = 0.0. Proportion of all state-tuned neurons that are also goal-progress tuned; 81% Two proportions test: N = 738 neurons, z = 29.5, P = 0.0. f) A histogram showing the distribution of significant goal-progress peaks amongst all neurons, all tasks and all states. Only neurons from concatenated double days that are significantly goal progress-tuned and have at least one significant goal-progress peak are shown (N = 873 neurons). The plot shows that such significantly goal-progress tuned cells have peaks throughout the entire range of goal progress values. Note that this plot spans goal-progress space, which is the lag between any two rewarded goals, rather than the full (multi-goal) task space. g) Regression coefficients for animal kinematics (from GLM in Fig. 2g). Two histograms showing the mean regression coefficient values for Speed (Left) and Acceleration (Right) as a regressor across task/state combinations for each neuron. One-sample T-test (two-sided) against 0: Speed: N = 1252 neurons, statistic=3.36, P = 8.01 × 10−4 df = 1251; Acceleration: N = 1252 neurons, statistic = −0.78, P = 0.438 df = 1251. h) Polar plots of task tuning and spatial maps for four example neurons that are tuned to both goal-progress and state. Each neuron is plotted across two tasks to illustrate spatial tuning (left two neurons) and lack thereof (right two neurons). i) The subregional distribution of neuron type coefficients along the medial wall of the frontal cortex in neuropixels recordings. One-way ANOVA: Left: Proportion of Goal progress neurons: F = 2.40, P = 0.143, df = 3; Middle: Proportion of state neurons F = 1.04, P = 0.425, dof=3; Right: Proportion of place-tuned neurons F = 18.8, P = 5.54 × 10−4, df = 3. Posthoc Tukey HSD tests (Two-tailed): IrL vs PrL P = 0.049; IrL vs ACC P = 0.000; IrL vs M2 statistic=0.003, PrL vs ACC P = 0.021. j) A plot of the mean task manifold derived from a Uniform Manifold Approximation and Projection (UMAP)-embedding along three dimensions restricted to only non-spatial neurons. Note that we use the most permissive threshold for spatial tuning here to ensure that we exclude even neurons with weak/residual spatial tuning. Any neuron that had a spatial regression coefficient above the 95th percentile of the null distribution was excluded from this analysis. The same manifold is shown twice: Left, goal-progress tuning along the manifold; right, state tuning along the same manifold. The entire task manifold is composed of goal-progress subloops. k) Quantifications of distances along the 3-dimensional UMAP-derived manifold - across different states and opposite goal-progress bin (left), across different states but for the same goal-progress bin (middle) or the distances across different states and same goal-progress bin for a shuffled control. N = 8 double-days - T-tests (two-sided) (with bonferroni correction): Across-goal progress vs within goal-progress: statistic =10.3, P = 5.45 × 10−5, df = 7; Across-goal progress vs permuted control: statistic =17.5, P = 1.47 × 10−6, df = 7; Within goal-progress vs permuted control: statistic =5.2, P = 0.004, df = 7 All error bars represent the standard error of the mean.

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