Figure 2. CDGI mediates the M1R modulation of dendritic excitability but not the M1R modulation of somatic excitability. (A and B) Sagittal sections through the brains of CDGI knockout mice in which the direct pathway was visualized (red) in D1-tdTomato mice (A) and the indirect pathway was visualized (green) in D2-GFP mice. (C) Sample somatic voltage changes evoked by 120pA current injections in iSPNs from WT (black) and CDGI-KO (red) before and after bath application of oxo-M (10 µM). (C-D) Current-response curves of iSPNs from WT (B, n=5 cells) and CDGI-KO mice (C, n=7 cells). Somatic excitability of iSPNs was similarly enhanced by oxo-M in WT and CDGI-KO. (E) Sample somatic recordings in response to 140pA current injections in dSPNs from WT (black) and CDGI KO (red) before and after bath application of oxo-M (10 µM). (F-H) Current-response curves of dSPNs from WT (E) and CDGI-KO (F) mice (n=4-6). (I) Trains of five EPSPs were evoked by stimulation of glutamatergic afferent fibers at 40 Hz. Oxo-M (10 µM) increased EPSP summation in iSPNs of WT, but not in CDGI-KO or when M1Rs were blocked by M1R antagonist VU0255035 in WT (5 M). (J) Box plot showing the effect of oxoM on synaptic summation. The EPSP5/EPSP1 ratio was increased by oxoM in iSPNs of WT (p = 0.002, Wilcoxon test; n = 10), but not in iSPNs of 27 CDGI-KO mice (p = 0.25, n = 9) or in iSPNs of WT mice in the presence of VU0255035 (p = 0.69, n = 6). (K) Box plot showing the effect of oxoM on the kinetics of synaptic response. The decay time constant of EPSP5 was significantly increased by oxoM in iSPNs of WT (p = 0.002); but not when CDGI was genetically deleted (p = 0.65) or when M1R was pharmacologically blocked (p = 0.84).