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. Author manuscript; available in PMC: 2023 Dec 27.
Published in final edited form as: Nature. 2022 Nov 9;611(7937):762–768. doi: 10.1038/s41586-022-05407-4

Extended Data Fig. 4. Supporting experiments for manipulating PKA activities using drug administration or PKI expression.

Extended Data Fig. 4.

a & b, PKA activity responses to Rp-8-Br0cAMPS (Rp) and H89 for dSPNs (a) and iSPNs (b). From left to right, n (neurons/mice) = 27/3 and 22/3 for dSPNs, and 33/4 and 24/4 for iSPNs. Two-tailed paired Student’s t-test, p = 6.9×10−10 and 2.7×10−5, dF = 26 and 21, t = −9.4 and −5.3 for panel a; and p = 4.0×10−6 and 6.3×10−5, dF = 32 and 23, t = −5.5 and −4.9 for panel b. c, Representative images of co-expression of PKI (red) and the PKA sensor tAKARα (green) in the same cells (top), and representative traces of enforced running-induced PKA activity in neurons of the mouse motor cortex without (bottom left) and with (bottom right) PKI expression. n (FOVs/mice) = 19/9 without PKI and 14/4 with PKI. d, Collective enforced running-induced PKA responses in neurons of mice without or with PKI expression. n (neurons/mice) = 124/9 for control and 30/4 for PKI. Boxes indicate 25th and 75th percentile, with black lines indicating median and whiskers indicating 2.7x standard deviation. Two-tailed unpaired Student’s t-test, p = 1.4×10−7; dF = 152; t = 5.5. e, Representative 3D reconstructions of PKI expression in Drd1a-cre (left) and Adora2a-cre (right) mice. Inj.: injection; proj.: projection; A: anterior; L: lateral; and D: dorsal. f & g, Accelerated rotarod training for mice with PKI or a non-functional PKI mutant (PKImut) expressed in dSPNs (f) or iSPNs (g). n (mice) = 11 for both groups for dSPNs and 10 for both groups for iSPNs. Two-tailed paired Student’s t-test, for first and second days, respectively, dF = 10 and 10, t = −3.3 and −3.2 for dSPNs; and dF = 9 and 9, t = −2.6 and −1.5 for iSPNs. h, Averaged travel velocity of mice with PKI or a non-functional PKI mutant (PKImut) expressed in dSPNs or iSPNs freely moving in an open-field box (37 × 37 cm). From left to right, n (neurons/mice) = 11, 11, 10, and 10. Two-tailed paired Student’s t-test, p = 0.03 and 0.18; dF = 10 and 9; t = 1.2 and −0.6. All error bars represent SEM and their centers represent the mean. n.s.: p > 0.05; *: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001.