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. 2022 Jun 23;11:e76051. doi: 10.7554/eLife.76051

Figure 1. Increased necessity of cortical association areas in complex versus simple decision tasks.

(A) Schematic overview of the behavioral tasks and task training sequences used in this study. Top row: One group of mice is trained in the simple task only. Middle row: Another group of mice is trained on the delay task and then transitioned to the simple task. Bottom row: Another group of mice is trained on the switching task and then transitioned to the simple task. The middle and bottom rows indicate complex training histories. (B) Top: Schematic of virtual reality behavioral setup. Bottom right: Schematic of optogenetic inhibition with bilateral target locations. Bottom left: Top view of Y-maze. Inhibition lasted from trial onset throughout maze traversal. (C) Left: Simple task schematic indicating two trial types (horizontal or vertical cues) and corresponding rewarded navigation decisions (running left or right). Corresponding VR screenshots at the trial start are below. Right: Top view of the two maze schematics. Water drops indicate hidden reward locations. (D) Left: Example session in the simple task showing mean performance for each inhibited location. Right: Performance in the simple task for each inhibited location across 45 sessions from 4 mice. Bars indicate mean ± standard error of the mean (SEM) of a bootstrap distribution of the mean. S1 p = 0.84; RSC p < 0.001; PPC p = 0.006; from bootstrapped distributions of ΔFraction Correct (difference from control performance) compared to 0, two-tailed test, α = 0.05 plus Bonferroni correction. *: p < 0.05; **: p < 0.01; ***: p < 0.001. Sessions per mouse: 11 ± 2. Trials per session: 53 ± 23 (control), 19 ± 8 (S1), 18 ± 9 (RSC), 20 ± 9 (PPC), mean ± standard deviation (SD). (E) Similar to (C), but for the delay task. (F) Similar to (D), but for the delay task. Sixty-two sessions from 7 mice. S1 p = 0.006; RSC p < 0.001; PPC p < 0.001. Sessions per mouse: 9 ± 4. Trials per session: 60 ± 15 (control), 16 ± 6 (S1), 15 ± 4 (RSC), 17 ± 5 (PPC), mean ± SD. (G) Left: Schematic of the switching task, utilizing the identical mazes as the simple task. The cue–choice associations from the simple task (Rule A) were switched within a session (to Rule B). Right: Behavioral performance from an example session. Dotted orange lines indicate rule switches. (H) Similar to (D), but for the switching task, Rule A trials only. 89 sessions from 6 mice. S1 p = 0.036; RSC p < 0.001; PPC p < 0.001. Sessions per mouse: 15 ± 5. Trials per session: 26 ± 9 (control), 8 ± 3 (S1), 7 ± 4 (RSC), 8 ± 3 (PPC), mean ± SD. (I) Comparison of inhibition effects (ΔFraction Correct) in the simple and the delay tasks for each cortical inhibition location. Bars indicate mean ± SEM of a bootstrap distribution of the mean; two-tailed comparisons of bootstrapped ΔFraction Correct distributions, α = 0.05. *: p < 0.05; **: p < 0.01; ***: p < 0.001. Same datasets as in (F, G). (J) Similar to (I), but for the simple versus switching task (Rule A trials only). Same datasets as in (F, H). The simple task data are the same as in (I). (K) Left: Comparison of performance on control trials across tasks, using only the first two laser-on blocks in each session. Bars indicate mean ± SEM of a bootstrap distribution of the mean. Delay versus simple p < 0.001; switching versus simple p < 0.001; two-tailed comparisons of bootstrapped Fraction Correct distributions, α = 0.05. *** p < 0.001. Right: The number of training sessions needed to reach performance criteria across tasks (Methods). Bars indicate mean ± SEM across mice, n = 4 for simple task, n = 5 for delay task, n = 6 for switching task. Both delay and switching task data were compared to the simple task data using an unpaired two-sided t-test. Delay versus simple p = 0.015; switching versus simple p = 0.006. *: p < 0.05, **: p < 0.01.

Figure 1.

Figure 1—figure supplement 1. Behavioral training stages and task transitions.

Figure 1—figure supplement 1.

(A) Behavioral training stages for mice trained on the simple task only. Top: In the initial training stage, to get used to running in the virtual environment, mice learned to run down a linear maze toward a checkerboard pattern to obtain a reward. Linear maze length was gradually increased across sessions. Left: The number of days spent in this training stage across mice and tasks (including mice from (B) (top) and (C) (top)). Error bars indicate mean ± standard error of the mean (SEM) across 13 mice. Middle: The second training stage was the simple task with 100% visually guided trials, meaning the correct choice to be made in each trial was indicated with a checkerboard pattern at the left or right maze end depending on the visual cue on the maze walls. Across sessions, the fraction of visually guided trials was gradually decreased (dotted arrow), until only 10% of trials were visually guided in the full simple task (bottom). Left: The number of training days that mice were trained on the simple task, regardless of the fraction of visually guided trials (mean ± SEM across 4 mice). Note that the number of training days is the overall number of days mice were run on the simple task prior to photoinhibition sessions, including sessions after they had reached high simple task performance levels. (B) Similar to (A), but for mice trained on the delay task. The first three training stages are the same as in (A). After full simple task training, mice were moved to the delay task. In this stage, the delay was gradually increased, and the visual cue was shortened across sessions. Left: The number of days spent on the delay stage (mean ± SEM across seven mice). Bottom: After delay task training and photoinhibition, five out of seven mice were transitioned to the simple task (see Figure 2). (C) Similar to (A), but for mice trained on the switching task. After initial linear maze training, the second training stage was the switching task with 100% visually guided trials. The fraction of visually guided trials was gradually decreased across sessions (dotted arrow). Right: The number of training days that mice were trained on the switching task, regardless of the fraction of visually guided trials (mean ± SEM across six mice). Bottom: After switching task training and photoinhibition, five out of six mice were transitioned to the simple task (see Figure 3).
Figure 1—figure supplement 2. Choice decoding from running, stability of inhibition effects and choice biases from inhibition across tasks.

Figure 1—figure supplement 2.

(A) Left: Decoding accuracy of the reported choice using instantaneous treadmill velocities and lateral position, binned along the maze’s long axis (5 cm bins) per task, using control trials only. Shading indicates mean ± standard error of the mean (SEM) across sessions. Dashed lines indicate the different maze segments. In the delay task, the choice-informative cue was only present in the first maze segment (stem first half). Right: First maze position (as a fraction of the maze long axis) at which decoding of choice exceeded 90%, approximating decision points in the maze. Error bars indicate mean ± SEM across sessions. Compared to simple task: delay task p = 1.91 × 10−06; switching task p = 0.74; two-sample t-test with α = 0.05. Sessions per task per mouse: 11± 2 (simple, four mice), 12 ± 5 (delay, seven mice), and 15 ± 5 (switching, six mice, Rule A trials only). (B) Maze decision positions are plotted versus the inhibition effects on task performance for each cortical inhibition location. Circles indicate individual sessions color coded by task as in (A). Black line: regression line, error bars: 95% confidence intervals. N sessions overall: 166 (S1), 167 (RSC), and 175 (PPC). (C) For each cortical inhibition location, the number of experienced simple task sessions is plotted versus the inhibition effect on performance in the simple task (n = 45 sessions). Circles indicate individual sessions. Black line: regression line, error bars: 95% confidence intervals. (D) Signed choice bias (left) and unsigned choice bias (right) for each inhibited location in the simple task. Line colors indicate different mice. Error bars indicate mean ± SEM across sessions. 11 ± 2 sessions per mouse. (E) Similar to (C), but for the delay task. N = 62 sessions. (F) Similar (D), but for the delay task. 12 ± 5 sessions per mouse. (G) Similar to (C), but for the switching task. N sessions = 61 (S1), 62 (RSC), and 70 (PPC). (H) Similar to (D), but for the switching task. 15 ± 5 sessions per mouse.
Figure 1—figure supplement 3. Performance after rule switches and inhibition effects in high-performance periods of Rule B in the switching task.

Figure 1—figure supplement 3.

(A) In the switching task, behavioral performance after rule switches across rules from eight mice total (middle, switches per mouse: 23 ± 18) and separately for each rule (right, switches per mouse per rule: 11 ± 9 (mean ± standard deviation [SD])). Fraction Correct was Gaussian filtered (window of seven trials, sigma of three trials). Error bars indicate mean ± standard error of the mean (SEM) across mice. Dashed line indicates chance level. (B) Comparison of number of trials needed to reach performance criterion (Methods) after switches to Rule A versus switches to Rule B. p = 0.18, two-sample t-test, n = 91 switches to Rule A and 93 switches to Rule B across eight mice. (C) Performance in high-performance periods of Rule B in the switching task for each inhibited location across 87 sessions from 6 mice. Bars indicate mean ± SEM of a bootstrap distribution of the mean. S1 p = 0.07; RSC p < 0.001; PPC p < 0.001; from bootstrapped distributions of ΔFraction Correct (difference from control performance) compared to 0, two-tailed test, α = 0.05 plus Bonferroni correction. ***: p < 0.001. Sessions per mouse: 15 ± 5. Trials per session: 29 ± 11 (control), 5 ± 5 (S1), 6 ± 5 (RSC), 7 ± 6 (PPC), mean ± SD. (D) Comparison of inhibition effects (ΔFraction Correct) in the simple task and the switching task (Rule B trials only) for each cortical inhibition location. Bars indicate mean ± SEM of a bootstrap distribution of the mean; two-tailed comparisons of bootstrapped ΔFraction Correct distributions, α = 0.05. **: p < 0.01; ***: p < 0.001. (E) Comparison of performance on control trials in the simple task and Rule B trials of the switching task, using only the first two laser-on blocks in each session. Bars indicate mean ± SEM of a bootstrap distribution of the mean. p < 0.001; two-tailed comparison of bootstrapped Fraction Correct distributions, α = 0.05. ***: p < 0.001.
Figure 1—figure supplement 4. Similar deficits from inhibition in a run-to-target task as in the simple task.

Figure 1—figure supplement 4.

(A) Schematic and virtual reality screenshots of run-to-target task showing left and right trials. (B) Performance in the run-to-target task for each inhibited location across 15 sessions from 3 mice. Bars indicate mean ± standard error of the mean (SEM) of a bootstrap distribution of the mean. S1 p = 0.85; RSC p < 0.001; PPC p = 0.16; from bootstrapped distributions of ΔFraction Correct (difference from control performance) compared to 0, two-tailed test, α = 0.05 plus Bonferroni correction. ***: p < 0.001. Sessions per mouse: 5 ± 2. Trials per session: 93 ± 11 (control), 26 ± 5 (S1), 24 ± 5 (RSC), 28 ± 6 (PPC), mean ± standard deviation (SD). (C) Comparison of performance on control trials in the simple task (same dataset as in Figure 1K) versus the run-to-target task using only the first two laser-on blocks in each session. Bars indicate mean ± SEM of a bootstrap distribution of the mean; p < 0.001, two-tailed comparison of bootstrapped Fraction Correct distributions, α = 0.05. ***: p < 0.001. Trials per session: 51 ± 23 (simple task), 93 ± 11 (run-to-target task), mean ± SD. (D) Comparison of inhibition effects (ΔFraction Correct) in the simple task (same dataset as in Figure 1F) and the run-to-target task for each cortical inhibition location. Bars indicate mean ± SEM of a bootstrap distribution of the mean; two-tailed comparisons of bootstrapped ΔFraction Correct distributions, α = 0.05.
Figure 1—figure supplement 5. Cue only or delay only inhibition in the delay task.

Figure 1—figure supplement 5.

(A) Left: Schematic of the delay task. Right: Inhibition was restricted to either the cue period only or the delay period only in a given session. (B) Performance in the delay task with cue only (blue, 48 sessions from 5 mice) or delay only (green, 45 sessions from 5 mice) inhibition for each inhibited location. Bars indicate mean ± standard error of the mean (SEM) of a bootstrap distribution of the mean. For cue only or delay only inhibition individually, inhibition performance was compared to control performance, two-tailed test, α = 0.05 plus Bonferroni correction. Cue only: S1 p = 0.09; RSC p < 0.001; PPC p < 0.001. Sessions per mouse: 10 ± 2. Trials per session: 59 ± 16 (control), 14 ± 6 (S1), 14 ± 5 (RSC), 15 ± 5 (PPC), mean ± standard deviation (SD). Delay only: S1 p = 0.27; RSC p < 0.001; PPC p < 0.001. Sessions per mouse: 9 ± 2. Trials per session: 61 ± 15 (control), 14 ± 5 (S1), 15 ± 4 (RSC), 15 ± 5 (PPC), mean ± SD. (C) Comparison of inhibition effects (ΔFraction Correct) in the simple task (same dataset as in Figure 1F) and the delay task with cue inhibition only for each cortical location. Bars indicate mean ± SEM of a bootstrap distribution of the mean; two-tailed comparisons of bootstrapped ΔFraction Correct distributions, α = 0.05. (D) Similar to (C), but for delay inhibition only in the delay task.
Figure 1—figure supplement 6. Performance on trials following inhibition and rule switching with inhibition during the feedback/ITI period.

Figure 1—figure supplement 6.

(A) Left: Schematic of the inhibition locations (same as in Figure 1). Middle: Inhibition lasted from trial onset throughout maze traversal. Right: As in Figure 1, inhibition target locations per trial were randomly interleaved. Analysis here used performance on control trials that directly followed inhibition of the labeled location on the preceding trial. (B) Performance on control trials immediately following an inhibition trial, for the simple task, for each inhibited location across 45 sessions from 4 mice. Bars indicate mean ± standard error of the mean (SEM) of a bootstrap distribution of the mean. S1 p = 1; RSC p = 1; PPC p = 1; from bootstrapped distributions of ΔFraction Correct (difference from control performance) compared to 0, two-tailed test, α = 0.05 plus Bonferroni correction. Sessions per mouse: 11 ± 2. Trials per session: 22 ± 12 (control), 8 ± 3 (S1), 8 ± 4 (RSC), 9 ± 4 (PPC), mean ± standard deviation (SD). (C) Similar to (B), except for the delay task. Sixty-two sessions from seven mice. S1 p = 1; RSC p = 0.12; PPC p = 0.50. Sessions per mouse: 9 ± 4. Trials per session: 29 ± 8 (control), 8 ± 3 (S1), 9 ± 4 (RSC), 7 ± 3 (PPC). (D) Similar to (B), except for the switching task (Rule A trials only). 89 sessions from 6 mice. S1 p = 0.66; RSC p = 0.27; PPC p = 0.19. Sessions per mouse: 15 ± 5. Trials per session: 13 ± 6 (control), 4 ± 2 (S1), 5 ± 2 (RSC), and 4 ± 2 (PPC). (E) Top: Schematic of the switching task. Bottom: Schematic of a single trial with inhibition during the feedback and ITI period. (F) Left: Schematic of PPC and control targets. Right top: Example behavioral performance in one session in the switching task. Right bottom: Inhibition blocks of 50 trials started after a rule switch, with inhibition during the feedback/ITI period. The same area was targeted on every trial. (G) Average performance after a rule switch with PPC (blue) or control (black) inhibition on every trial during the feedback/ITI. Thirty-three sessions from four mice (8 ± 2 sessions per mouse, mean ± SD). Shading indicates mean ± SEM across sessions. Thin lines indicate single sessions. Fraction Correct was Gaussian filtered (window of seven trials, sigma of three trials) and smoothed again with a moving average filter of three trials for plotting. (H) Comparison of mean performance with PPC versus control inhibition after a rule switch in bins of 10 trials. Error bars indicate mean ± SEM across sessions, gray lines show single sessions (n = 33). Paired two-sided t-tests. p (trials 1–10): 0.42; p (trials 11–20): 0.43; p (trials 21–30): 0.64; p (trials 31–40): 0.66; p (trials 41–50): 0.34.