Fig. 3. Emergence of distinct populations following learning depends on apical dendritic activity of L5 pyramidal neurons.

(A), (B) Z-score normalized firing rate PSTHs of L5 pyramidal neurons in S1 of expert and untrained rats, respectively. Z-scores for cells with no spikes during pre-stimulus period could not be computed and therefore not included in this analysis. (C) Left, average PSTHs of L5^ON, L5^OFF and L5^NR neurons (total n=273 cells) in expert rats. Gray box: μStim. Right, the fraction of L5^ON, L5^OFF and L5^NR neurons. (D) Two-photon Ca²⁺ imaging from the apical dendrites of L5 pyramidal neurons in Rbp4-cre transgenic mice during the μStim task. (E) Horizontal imaging plane (upper) (~150 μm from pia) and average Ca²⁺ responses (lower) for all trials from an example dendrite marked with a yellow arrow. (F) Ca²⁺ responses in an apical dendrite marked in (E) during 180 trials of hit trials. (G) Left, Average peri-stimulus Ca²⁺ responses in ON, OFF and NR dendrites (total n=318 dendrites) during hit trials. Gray box: μStim. Right, fraction of ON, OFF and NS dendrites. (H) Experimental designs for manipulating dendritic activity during μStim task. Upper, baclofen application in superficial layers of S1 in wild-type mice. Lower, optogenetic activation of SST+ interneurons during μStim task in SST::ChR2 transgenic mice. The surface of the craniotomy was illuminated with blue light (465 nm) (See Methods). (I) Cumulative learning curve of control mice (n=20, black), baclofen-treated mice (n=6, blue) and SST::ChR2 mice (n=6, purple) during the first session. (J) Normalized learning score of control, baclofen-treated and SST::ChR2 mice at the first session. Each dot corresponds to individual mice and black line indicates mean. Wilcoxon rank-sum test against control, *** p<0.001, *p=0.01.