(A) Locomotion before and after CNO or vehicle administration. Left: Example 3D traces showing head position during 30 min recordings before and after i.p. injection of CNO (blue) or vehicle (orange). Right: group-wise quantification of distance travelled shows that CNO- and vehicle-treated subjects did not respond differently to i.p. injections (p=0.16 for interaction of time and treatment, n = 6 and 7 mice). Subjects non-specifically decreased locomotor activity following the i.p. injection procedure (F(11,1) = 49.01, p=2.27×10−5, n = 6 and 7 mice). (B) Representative single-unit waveforms classified as FSIs (top, green) and SPNs (bottom, purple). (C) Waveform properties used for cell type classification. Left: FSI waveforms display a shorter spike width relative to those of SPNs (t(64) = 30.67, p=5.53×10−40, n = 23 FSIs and 43 SPNs). Right: FSIs display higher firing rates than SPNs (t(64) = 4.32, p=0.000056, n = 23 FSIs and 43 SPNs). (D) Classification of single units as FSIs (green) or SPNs (purple) by spike width and firing rate. (E) Time course showing FSI firing rates before (white background) and after (tan background) i.p. injection of CNO (blue) or vehicle (orange). CNO injection decreased FSI firing rate relative to vehicle (interaction between drug and time: F(5,105) = 2.51, p=0.034, n = 13 and 10 FSIs). (F) SPN responses to CNO or vehicle as in (E). CNO injection increased SPN firing rate relative to vehicle (interaction between drug and time: F(5,205) = 2.63, p=0.025, n = 23 and 20 SPNs). (G) Linear regression of fold-change (log2 post/pre) in firing rate after CNO (left) or vehicle (right) injection against the baseline fraction of ISIs in the gamma frequency band. SPNs with higher fractions of gamma-frequency ISIs at baseline are more likely to decrease firing rate when FSIs are inhibited with CNO (r(22) = −0.59, p=0.0032, n = 23 cells) whereas vehicle caused no change in firing rate that could be predicted by baseline fraction of gamma ISIs (p=0.92, n = 20 cells). *p<0.05. Data are represented as mean ± SEM. Example units before and after CNO shown in Figure 5—figure supplement 1.