Fig. 7: Abolition of ChC inhibition impairs the refinement of direction coding and motor learning.
From: An adaptive behavioral control motif mediated by cortical axo-axonic inhibition
a, Generation of Nkx2.1-2a-CreER::Flex-FlpO mice. Nkx2.1-2a-CreER::Flex-FlpO mice were generated by crossing Nkx2.1-2a-CreER with ROSA-Flex-FlpO mouse lines. The targeting vector containing Rosa26 homology arms, a CAG promoter and a FLEX-Flp cassette was constructed. Similarly to Nkx2.1-2a-CreER::Ai14, Tmx was administered to timed pregnant Swiss Webster females by oral gavage at E17. b, Schematic for selective abolition of GABA release from ChCs in M2 by expressing TeTxLC in ChC-Flp mice (Nkx2.1-2a-CreER::Flex-FlpO mice). c, A representative image of ChC neurons expressing TeTxLC-HA and neighboring neurons expressing GCaMP6s in Nkx2.1-2a-CreER::Flex-FlpO mice (left, n = 9 mice) and post hoc validation of ChCs’ axonal projection to the AIS of neighboring PyNs by AnKG staining (right). Yellow arrowheads indicate putative cartridges associated with AISs. d–l, Behavioral impact of ChC manipulation. d, Representative movement traces of mice in ChC control (top) and ChC-TeTxLC (bottom) navigating on the multi-textured floating ball maze in session 7 (100 s). A circle with a dashed line indicates the goal spot on the ball. Heat map and contour lines of the times of mice spent on the location are presented. e, Average movement speed (n = 9 mice for ChC-TeTxLC group; n = 8 mice for ChC control group; two-way repeated-measures ANOVA, Fgroup = 1.16, P = 0.32). f, Average movement acceleration (two-way repeated-measures ANOVA, Fgroup = 3.22, P = 0.12). g, Average number of successes obtained in training sessions (two-way repeated-measures. ANOVA, Fgroup = 8.54, P = 0.011). h, Average latency to reward (two-way repeated-measures ANOVA, Fgroup = 7.81, P = 0.0136). i, Average goal proximity (two-tailed t-test, t = −2.52, P = 0.017 for ChC control; t = 1.38, P = 0.177 for ChC-TeTxLC). j, Movement accuracy (two-tailed t-test, t = −3.80, P = 6.67 × 10−4 for ChC control; t = −1.05, P = 0.30 for ChC-TeTxLC). k, Cumulative turning angle over time in sessions 1 and 7. l, Comparison of cumulative turning angle between ChC-TeTxLC and ChC control (two-tailed t-test, t = −3.21, P = 3.51 × 10−3 for ChC control; t = −1.39, P = 0.175 for ChC-TeTxLC). m, Example tuning curves of individual premotor neurons for movement. Data are sorted from the location of peak likelihood probability P(active|MD). n, Normalized percentage of active cells in the population as a function of distance from the PD (n = 378 cells for session 1, n = 416 cells for session 7 in ChC-TeTxLC; n = 665 cells for session 1, n = 689 cells for session 7 in ChC control). o, Changes of the percentage of active cells from session 1 to session 7 (n = 5 mice for ChC-TeTxLC, two-tailed Student’s t-test. t = 0.56, P = 0.606; n = 4 mice for ChC control. t = −17.97, P = 3.76 × 10−4). p, Pairwise correlations with respect to ΔPD normalized by session 1 (angular difference in PD between neuronal pairs, n = 15,028 pairs for session 1, n = 22,589 pairs for session 7 for ChC-TeTxLC; n = 57,956 pairs for session 1, n = 62,104 pairs for session 7 for ChC control). q, Changes in posterior probabilities, P(MD|active), normalized by chance level (dashed line) as a function of distance from MD with learning. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; error bars and shading indicate s.e.m. In the box plot, the midline, box size and whisker indicate median, 25th–75th percentile and 10th–90th percentile, respectively. 2p, two-photon; CW, clockwise; CCW, counterclockwise; a.u., arbitrary units.
