Extended Data Figure 4. Causal evidence for task-specific sequential PFC activity maintaining rule representation.

(a) Impact of bilateral optogenetic enhancement of local inhibition on PFC rule tuning and behavior. (a1) Raster and PSTH examples of neurons tuned either early or late in the delay (blue shading indicates laser presentation), shows loss of tuning with minimal impact on overall spiking (see Extended Data Figure 3i for quantification of laser on spike rates). (a2) Laser impact on population tuning measured by averaged peak sizes over the delay (n = 94 neurons, 3 mice; example quantification in Extended Data Figure 3j; see method for peak quantification) (a3) Laser impact on population rule information from the same neurons in a2. (a4) Laser impact on behavior (n = 12 sessions; 4 from each mouse) (b-d) Temporally-limited optogenetic manipulations show that later PFC tuning is dependent on early tuning. (b) Manipulation limited to the first 250 ms is sufficient to mimic effect of full delay period suppression on neural tuning with a smaller impact on behavior likely due to a smaller laser dose and being close to the optical fibers (n = 52 neurons, 12 sessions). (c) Effect in b persists even when rule presentation period is spared (n = 46 neurons, 12 sessions). (d) Late laser only impacts late activity (n = 53 neurons, 12 sessions). (e) Cartoon of experimental comparison of the effect of sensory selection rule presentation inside and outside of the task. (f1) Example of two neurons that display tuning following rule-related cue presentation inside the task but not outside of it. (f2) Group quantification for population tuning in f1 (n = 52 neurons from 3 mice). For peak size, shaded error regions show the 95% CIs of the measure, while the gray bar denotes the subsampled bootstrapped 95% CIs for baseline error estimate. For rule information shaded areas indicate bootstrapped 95% CIs. Wilcoxon rank-sum test was used for all behavioral comparisons.