Figure 3A
Weight analysis of ctrl and cKO mice |
Normally distributed |
Two-way ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 14(M = 8, F = 6)cKO N = 23(M = 15, F = 8) |
Interaction: p = 0.996, F(4,158) = 0.0447Week: p < 0.001, F(4,158) = 79.8Genotype: p = 0.032, F(1,158) = 4.67Multiple comparisonsCtrl vs cKOw4 p = 0.908; 95% CI: –3.55 to 1.75w5 p = 0.966; 95% CI: –2.70 to 1.57w6 p = 0.876; 95% CI: –2.91 to 1.35w7 p = 0.720; 95% CI: –3.19 to 1.15w8 p = 0.783; 95%CI: –3.11 to 1.23 |
Figure 3B
Baseline locomotion of ctrl and cKO mice for 30 min in 5-min bins |
Normally distributed |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 17(M = 8, F = 9)cKO N = 17(M = 13, F = 4) |
Interaction: p = 0.256, F(5,160) = 1.33Time: p < 0.001, F(5,160) = 69.5Genotype: p = 0.535, F(1,32) = 0.00912Multiple comparisonsCtrl vs cKO5 p > 0.999; 95% CI: –287 to 21110 p > 0.999; 95% CI: –217 to 28215 p = 0.952; 95% CI: –170 to 32920 p > 0.999; 95% CI: –236 to 26325 p = 0.886; 95% CI: –346 to 15330 p = 0.993; 95% CI: –195 to 304 |
Figure 3C
Sucrose preference of ctrl and cKO mice for 1%, 3%, and 10% sucrose solutions |
Normally distributed |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 14(M = 8, F = 6)cKO N = 21(M = 13, F = 8) |
Interaction: p = 0.475, F(2,66) = 0.752Concentration: p < 0.001, F(2,66) = 151Genotype: p = 0.297, F(1,33) = 1.12Multiple comparisonsCtrl vs cKO1% p > 0.999; 95% CI: –5.21 to 5.693% p = 0.294; 95% CI: –1.83 to 9.0810% p = 0.991; 95% CI: –4.85 to 6.05 |
Figure 3D
Ethanol preference of ctrl and cKO mice for 3%, 6%, and 10% ethanol concentrations |
Normally distributed |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 14(M = 7, F = 7)cKO N = 14(M = 6, F = 8) |
Interaction: p = 0.129, F(2,52) = 2.13Concentration: p < 0.001, F(2,52) = 14.2Genotype: p = 0.334, F(1,26) = 0.969Multiple comparisonsCtrl vs cKO3% p = 0.983; 95% CI: –9.31 to 7.116% p = 0.453; 95% CI: –3.68 to 12.710% p = 0.396; 95% CI: –3.38 to 13.0Ctrl3% vs 6% p < 0.001; 95% CI: –14.7 to –3.453% vs 10% p < 0.001; 95% CI: –16.9 to –5.586% vs 10% p = 0.733; 95% CI: –7.78 to 3.52cKO3% vs 6% p = 0.354; 95% CI: –9.11 to 2.183% vs 10% p = 0.072; 95% CI: –10.9 to 0.3546% vs 10% p = 0.814; 95% CI: –7.47 to 3.82 |
Figure 3E
Injection-induced locomotion for ctrl and cKO mice after saline and 5, 10, and 20 mg/kg injections of cocaine |
Normally distributed |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 14(M = 8, F = 6)cKO N = 21(M = 13, F = 8) |
Interaction: p = 0.396, F(3,99) = 1Session: p < 0.001, F(3,99) = 108Genotype: p = 0.208, F(1,33) = 1.65Multiple comparisonsCtrl vs cKOSaline p = 0.966; 95% CI: –3437 to 54365 mg/kg. p = 0.962; 95% CI: –3410 to 546410 mg/kg. p = 0.887; 95% CI: –3015 to 585820 mg/kg. p = 0.152; 95% CI: –802 to 8071 |
Figure 3F
Amphetamine- induced (3 mg/kg) locomotion under a sensitization protocol for ctrl and cKO mice |
Normally distributed |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 17(M = 8, F = 9)cKO N = 17(M = 13, F = 4) |
Interaction: p < 0.001, F(5,160) = 4.79Session: p < 0.001, F(5,160) = 40.9Genotype: p = 0.005, F(1,32) = 9.09Multiple comparisonsCtrl vs cKODay1 p > 0.999; 95% CI: –13,977 to 12,091Day2 p = 0.266; 95% CI: –3371 to 22,696Day3 p = 0.063; 95% CI: –407 to 25,661Day4 p = 0.011; 95% CI: –2481 to 28,549Day5 p < 0.001; 95% CI: –6873 to 32,941Day17 p = 0.029; 95% CI: –928 to 26,996 |
Figure 3HCocaine (20 mg/kg, i.p) CPP for ctrl and cKO mice |
Normally distributed |
Unpaired t test |
Ctrl N = 12 (M = 6, F = 6)cKO N = 15 (M = 6, F = 9) |
t testctrl vs cKOp = 0.860; 95% CI: –162.0 to 136.1 |
Figure 3H, bottom panelAmphetamine (3 mg/kg, i.p.) CPP for ctrl and cKO mice |
Assumed normality |
Unpaired t test |
Ctrl N = 13 (M = 6, F = 7)cKO N = 16 (M = 9, F = 7) |
t testctrl vs cKOp = 0.744; 95% CI: –365.5 to 264.3 |
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Figure 3ICocaine-induced locomotion during the CPP for ctrl and cKO mice |
Assumed normality |
Two-way RM ANOVA followed by Sidak’s multiple comparison test |
Ctrl N = 12 (M = 6, F = 6)cKO N = 15 (M = 6, F = 9) |
Interaction: p = 0.652, F(3,75) = 0.5Session: p = 0.006, F(3,75) = 4.4Genotype: p = 0.031, F(1,25) = 5.2Multiple comparisonsCtrl vs cKOInjection 1: p = 0.373; 95% CI: –6850 to 1526Injection 2: p = 0.067; 95% CI: –8185 to 191Injection 3: p = 0.115; 95% CI: –7818 to 558Injection 4: p = 0.475; 95% CI: –6591 to 1785 |
Figure 3K, bottom panelAmphetamine-induced locomotion during the CPP for ctrl and cKO mice |
Normally distributed |
Mixed-effects model (REML) followed by Sidak’s multiple comparison test |
Ctrl N = 15 (M = 7, F = 8)cKO N = 17 (M = 10, F = 7) |
Interaction: p = 0.567, F(3,85) = 0.680Session: p < 0.001, F(3,85) = 24.0Genotype: p = 0.803, F(1,30) = 0.0631Multiple comparisonsCtrl vs cKOInjection 1: p = 0.941; 95% CI: –2522 to 1473Injection 2: p = 0.931; 95% CI: –1431 to 2517Injection 3: p = 0.995; 95% CI: –1783 to 2331Injection 4: p = 0.989; 95% CI: –1671 to 2327 |
Figure 6D, leftOptically evoked DA release in NAcSh of DAT-, NEX-, and Calb2-Cre mice injected with ChR2 or eYFP |
Normally distributed |
Unpaired t test |
10 observations for each group and virusDAT-Cre/Chr2 N = 2(M = 0, F = 2)DAT-Cre/eYFP N = 2(M = 1, F = 1)NEX-Cre/Chr2 N = 3(M = 2, F = 1)NEX-Cre/eYFP N = 2(M = 0, F = 2)Calb2-Cre/Chr2 N = 3(M = 1, F = 2)Calb2-Cre/eYFP N = 2(M = 0, F = 2) |
t testDAT-Cre/ChR2 vs DAT-Cre/eYFPp < 0.0001; 95% CI: –1.272 to –0.6540NEX-Cre/ChR2 vs NEX-Cre/eYFPp < 0.0001; 95% CI: –0.6289 to –0.2909Calb2-Cre/ChR2 vs Calb2-Cre/eYFPp = 0.0148; 95% CI: –0.01602 to –0.001988 |
Figure 6D, rightOptically evoked DA release in OT of DAT-, NEX-, and Calb2-Cre mice injected with ChR2 or eYFP |
Normally distributed |
Unpaired t test |
As above |
t testDAT-Cre/ChR2 vs DAT-Cre/eYFPp < 0.0001; 95% CI: –0.2354 to –0.1810NEX-Cre/ChR2 vs NEX-Cre/eYFPp = 0.0049; 95% CI: –0.01295 to –0.002704Calb2-Cre/ChR2 vs Calb2-Cre/eYFPp = 0.0002; 95% CI: –0.02022 to –0.007554 |
Figure 7D, left panelOptically evoked EPSCs in NAcSh of NEX-Cre/ChR2 mice before (control) and after DNQX bath application |
Assumed normality |
Paired t test |
6 cells from 3 NEX-Cre/ChR2 mice(M = 3, F = 0) |
p = 0.0481; 95% CI: –61.86 to –0.3739 |
Figure 7D, right panelOptically evoked EPSCs in OT of Calb2-Cre/ChR2 mice before (control) and after DNQX bath application |
Assumed normality |
Paired t test |
5 cells from 3 Calb2-Cre/ChR2 mice(M = 2, F = 1) |
p = 0.0456; 95% CI: –89.88 to –1.444 |
Figure 8B, leftBehavioral analysis of DAT-Cre/ChR2 mice throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 10(M = 2, F = 8) |
Interaction: p < 0.001, F(12,108) = 33Day: p = 0.435, F(6,54) = 1Compartment: p < 0.001, F(2,18) = 51.8Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.513; 95% CI: –38.4 to –6.29Day3 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 21.7 to 66.4Paired vs neutral p < 0.001; 95% CI: 35.7 to 80.4Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 37.6 to 82.3Paired vs neutral p < 0.001; 95% CI: 47.3 to 92.0Day5 (CR)Paired vs unpaired p < 0.001; 95% CI: 11.5 to 56.1Paired vs neutral p < 0.001; 95% CI: 26.7 to 71.4Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –65.7 to –21.0Paired vs neutral p < 0.001; 95% CI: 34.4 to 79.1Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –85.0 to –40.4Paired vs neutral p < 0.001; 95% CI: 43.1 to 87.7Day8 (CR)Paired vs unpaired p < 0.001; 95% CI: –67.2 to –22.5Paired vs neutral p < 0.001; 95% CI: 33.6 to 78.3 |
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Reversal parameters:Day3 paired vs Day6 unpaired p < 0.001; 95% CI: 22.8 to 67.4Day3 paired vs Day7 unpaired p < 0.001; 95% CI: 32.5 to 77.2Day4 paired vs Day6 unpaired p < 0.001; 95% CI: 32.3 to 76.9Day4 paired vs Day7 unpaired p < 0.001; 95% CI: 42.0 to 86.7Day5 paired vs Day8 unpaired p < 0.001; 95% CI: 17.5 to 62.2 |
Figure 8B, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for DAT-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 10(M = 2, F = 8) |
Compartment p < 0.001, F(2,6) = 166Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: 41.1 to 63.9Paired vs neutral p < 0.001; 95% CI: 51.7 to 74.5Unpaired vs neutral p = 0.066; 95% CI: –0.808 to 22.0 |
Extended Data Figure 8-1A, leftBehavioral analysis of DAT-Cre-negative mice injected with AAV-ChR2 throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 3(M = 0, F = 3) |
Interaction: p = 0.562, F(12,24) = 0.898Day: p = 0.569, F(6,12) = 0.830Compartment: p = 0.102, F(2,4) = 4.26Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.010; 95% CI: –49.6 to –4.05Day3 (RT-PP)Paired vs unpaired p = 0.074; 95% CI: 44.5 to 1.05Paired vs neutral p = 0.292; 95% CI: –5.3 to 40.3Day4 (RT-PP)Paired vs unpaired p = 0.236; 95% CI: –41.0 to 4.57Paired vs neutral p = 0.055; 95% CI: –0.241 to 45.3Day5 (CR)Paired vs unpaired p = 0.074; 95% CI: –44.5 to 1.08Paired vs neutral p = 0.204; 95% CI: –4.08 to 41. 5Day6 (RT-PP)Paired vs unpaired p = 0.998; 95% CI: –30.3 to 15.3Paired vs neutral p < 0.001; 95% CI: 12.0 to 57.6Day7 (RT-PP)Paired vs unpaired p = 0.863; 95% CI: –34.5 to 11.0Paired vs neutral p = 0.001; 95% CI: 9.18 to 54.8Day8 (CR)Paired vs unpaired p = 0.012; 95% CI: –49.2 to –3.6Paired vs neutral p < 0.001; 95% CI: 22.5 to 68.1Reversal parameters:Day3 paired vs Day6 unpaired p = 0.995; 95% CI: –30.8 to 14.8Day3 paired vs Day7 unpaired p > 0.999; 95% CI: –27.0 to 18.5Day4 paired vs Day6 unpaired p > 0.999; 95% CI: –28.0 to 17.6Day4 paired vs Day7 unpaired p > 0.999; 95% CI: –24.2 to 21.4Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –21.3 to 24.3 |
Extended Data Figure 8-1A, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for DAT-Cre-negative/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 3(M = 0, F = 3) |
Compartment p < 0.001, F(2,6) = 48.7Multiple comparisonsPaired vs unpaired p = 0.358; 95% CI: –15.8 to 5.46Paired vs neutral p < 0.001; 95% CI: 16.1 to 37.3Unpaired vs neutral p < 0.001; 95% CI: 21.2 to 42.5 |
Extended Data Figure 8-1B, leftBehavioral analysis of DAT-Cre/eYFP throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 3(M = 0, F = 3) |
Interaction: p = 0.677, F(12,24) = 0.767Day: p = 0.935, F(6,12) = 0.281Compartment: p = 0.004, F(2,4) = 27.9Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p < 0.001; 95% CI: –62.8 to –22.5Day3 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –64.9 to –24.6Paired vs neutral p = 0.198; 95% CI: –3.52 to 36.7Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –63.5 to –23.2Paired vs neutral p = 0.222; 95% CI: –3.85 to 36.4Day5 (CR)Paired vs unpaired p < 0.001; 95% CI: –65.9 to –25.6Paired vs neutral p = 0.251; 95% CI: –4.21 to 36.1Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –70.7 to –30.5Paired vs neutral p < 0.001; 95% CI: 45.8 to 86.1Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –55.5 to –15.2Paired vs neutral p < 0.001; 95% CI: 31.3 to 71.6Day8 (CR)Paired vs unpaired p < 0.001; 95% CI: –66.1 to –25.8Paired vs neutral p < 0.001; 95% CI: –42.7 to 82.9 |
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Reversal parameters:Day3 paired vs Day6 unpaired p > 0.999; 95% CI: –17.8 to 22.5Day3 paired vs Day7 unpaired p > 0.999; 95% CI: –23.1 to 17.2Day4 paired vs Day6 unpaired p > 0.999; 95% CI: –17.4 to 22.9Day4 paired vs Day7 unpaired p > 0.999; 95% CI: –22.7 to 17.5Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –20.4 to 19.9 |
Extended Data Figure 8-1B, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for DAT-Cre/eYFP mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 3(M = 0, F = 3) |
Compartment p = 0.127, F(2,6) = 2.97Multiple comparisonsPaired vs unpaired p > 0.999; 95% CI: –55.6 to 54.5Paired vs neutral p = 0.171; 95% CI: –17.5 to 92.6Unpaired vs neutral p = 0.165; 95% CI: –16.9 to 93.1 |
Extended Data Figure 8-1C, leftBehavioral analysis of DAT-Cre controls (pooled) throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 6(M = 0, F = 6) |
Interaction: p = 0.494, F(12,60) = 0.963Day: p = 0.929, F(6,30) = 0.306Compartment: p < 0.001 F(2,10) = 18.6Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p < 0.001; 95% CI: –48.6 to –20.8Day3 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –47.1 to –19.4Paired vs neutral p = 0.004; 95% CI: 3.15 to 30.9Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –44.7 to –16.9Paired vs neutral p < 0.001; 95% CI: 5.52 to 33.3Day5 (CR)Paired vs unpaired p < 0.001; 95% CI: –47.6 to –19.8Paired vs neutral p = 0.003; 95% CI: 3.42 to 31.2Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –42.9 to –15.1Paired vs neutral p < 0.001; 95% CI: 36.5 to 64.3Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –37.4 to –9.64Paired vs neutral p < 0.001; 95% CI: 27.8 to 55.6Day8 (CR)Paired vs unpaired p < 0.001; 95% CI: –50.1 to –22.3Paired vs neutral p < 0.001; 95% CI: 40.2 to 67.9Reversal parameters:Day3 paired vs Day6 unpaired p > 0.999; 95% CI: –16.7 to 11.1Day3 paired vs Day7 unpaired p > 0.999; 95% CI: –17.5 to 10.3Day4 paired vs Day6 unpaired p > 0.999; 95% CI: –15.1 to 12.7Day4 paired vs Day7 unpaired p > 0.999; 95% CI: –15.9 to 11.9Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –13.3 to 14.5 |
Extended Data Figure 8-1C, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for DAT-Cre control mice (pooled) |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 6(M = 0, F = 6) |
Compartment p = 0.015, F(2,6) = 9.27Multiple comparisonsPaired vs unpaired p = 0.946; 95% CI: –30.6 to 24.8Paired vs neutral p = 0.028; 95% CI: 4.44 to 59.8Unpaired vs neutral p = 0.019; 95% CI: 7.30 to 62.7 |
Extended Data Figure 8-1E, leftBehavioral analysis of DAT-Cre/ChR2 mice tested on high power, throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 10(M = 2, F = 8) |
Interaction: p < 0.001, F(12,36) = 22.6Day: p = 0.455, F(6,18) = 1Compartment: p < 0.001, F(2,6) = 105Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p > 0.999; 95% CI: –45.7 to 26.7Day3 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 26.2 to 98.6Paired vs neutral p < 0.001; 95% CI: 38.5 to 111Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 42.7 to 115Paired vs neutral p < 0.001; 95% CI: 47.1 to 119Day5 (CR)Paired vs unpaired p < 0.001; 95% CI: 17.4 to 89.8Paired vs neutral p < 0.001; 95% CI: 16.5 to 88.8Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –98.0 to –25.6Paired vs neutral p < 0.001; 95% CI: 36.5 to 109Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –109 to –37.0Paired vs neutral p < 0.001; 95% CI: 42.3 to 115Day8 (CR)Paired vs unpaired p = 0.407; 95% CI: –62.5 to 9.72Paired vs neutral p = 0.030; 95% CI: 1.98 to 74.3 |
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Reversal parameters:Day3 paired vs Day6 unpaired p < 0.001; 95% CI: 26.5 to 98.9Day3 paired vs Day7 unpaired p < 0.001; 95% CI: 32.1 to 104Day4 paired vs Day6 unpaired p < 0.001; 95% CI: 34.8 to 107Day4 paired vs Day7 unpaired p < 0.001; 95% CI: 40.5 to 113Day5 paired vs Day8 unpaired p < 0.001; 95% CI: 4.15 to 76.5 |
Extended Data Figure 8-1E, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for DAT-Cre/ChR2 mice under high power stimulation |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 0, F = 4) |
Compartment p < 0.001, F(2,6) = 404Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: 59.9 to 78.2Paired vs neutral p < 0.001; 95% CI: 68.1 to 86.5Unpaired vs neutral p = 0.074; 95% CI: –0.934 to 17.4 |
Figure 8C, leftBehavioral analysis of Vglut2-Cre/ChR2 mice throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 2, F = 5) |
Interaction: p < 0.001, F(12,72) = 16.1Day: p = 0.181, F(6,36) = 1.58Compartment: p < 0.001, F(2,12) = 40.9Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p > 0.999; 95% CI: –28.1 to 26.6Day3 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –71.9 to –17.2Paired vs neutral p > 0.999; 95% CI: –18.0 to 36.7Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –68.1 to –13.4Paired vs neutral p > 0.997; 95% CI: –16.9 to 37.8Day5 (CR)Paired vs unpaired p = 0.998; 95% CI: –37.8 to 16.9Paired vs neutral p = 0.019; 95% CI: 2.42 to 57.1Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 32.9 to 87.6Paired vs neutral p > 0.999; 95% CI: –28.8 to 25.9Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 27.0 to 81.7Paired vs neutral p > 0.999; 95% CI: –28.9 to 25.8Day8 (CR)Paired vs unpaired p = 0.783; 95% CI: –10.8 to 43.9Paired vs neutral p = 0.055; 95% CI: –0.268 to 54.4Reversal parameters:Day3 paired vs Day6 unpaired p < 0.001; 95% CI: –78.7 to –24.1Day3 paired vs Day7 unpaired p < 0.001; 95% CI: –74.8 to –20.1Day4 paired vs Day6 unpaired p < 0.001; 95% CI: –77.1 to –22.4Day4 paired vs Day7 unpaired p < 0.001; 95% CI: –73.2 to –18.5Day5 paired vs Day8 unpaired p = 0.952; 95% CI: –41.0 to 13.7 |
Figure 8C (right) time spent in paired, unpaired and neutral compartments during the 4 RT-PP days for Vglut2-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 2, F = 5) |
Compartment p < 0.001, F(2,6) = 162Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: –60.2 to –39.7Paired vs neutral p = 0.469; 95% CI: –6.08 to 14.5Unpaired vs neutral p < 0.001; 95% CI: 43.9 to 64.4 |
Figure 8D, leftBehavioral analysis of Calb2-Cre/ChR2 mice throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 0, F = 7) |
Interaction: p = 0.163, F(12,72) = 1.45Day: p = 0.567, F(6,36) = 0.813Compartment: p < 0.001, F(2,12) = 27Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.096; 95% CI: –33.3 to 1.13Day3 (RT-PP)Paired vs unpaired p = 0.343; 95% CI: –30.6 to 3.82Paired vs neutral p = 0.010; 95% CI: 2.52 to 37.0Day4 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –21.1 to 13.4Paired vs neutral p < 0.001; 95% CI: 8.22 to 42.7Day5 (CR)Paired vs unpaired p > 0.999; 95% CI: 13.4 to 47.9Paired vs neutral p < 0.001; 95% CI: –15.7 to 18.8Day6 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –18.2 to 16.2Paired vs neutral p < 0.001; 95% CI: 13.0 to 47.5Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –17.6 to 16.9Paired vs neutral p > 0.999; 95% CI: 10.8 to 45.2Day8 (CR)Paired vs unpaired p < 0.001; 95% CI: –13.1 to 21.3Paired vs neutral p > 0.999; 95% CI: 7.45 to 41.9 |
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Reversal parameters:Day3 paired vs Day6 unpaired p = 0.991; 95% CI: –24.6 to 9.91Day3 paired vs Day7 unpaired p = 0.995; 95% CI: –24.2 to 10.2Day4 paired vs Day6 unpaired p > 0.999; 95% CI: –19.5 to 15.0Day4 paired vs Day7 unpaired p > 0.999; 95% CI: –19.1 to 15.3Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –17.2 to 17.3 |
Figure 8D, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for Calb2-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 0, F = 7) |
Compartmentp < 0.001, F(2,6) = 90.1Multiple comparisonsPaired vs unpaired p = 0.297; 95% CI: –11.4 to 3.42Paired vs neutral p < 0.001; 95% CI: 18.5 to 33.3Unpaired vs neutral p < 0.001; 95% CI: 22.4 to 37.3 |
Extended Data Figure 8-1FBehavioral analysis of Calb2-Cre/ChR2 mice tested on high power, throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 0, F = 7) |
Interaction: p = 0.927, F(12,72) = 0.469Day: p = 0.661, F(6,36) = 0.688Compartment: p = 0.001, F(2,12) = 12.5Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.104; 95% CI: –33.5 to 1.28Day3 (RT-PP)Paired vs unpaired p = 0.995; 95% CI: –24.4 to 10.4Paired vs neutral p = 0.019; 95% CI: 1.56 to 36.3Day4 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –22.6 to 12.2Paired vs neutral p < 0.001; 95% CI: 47.1 to 119Day5 (CR)Paired vs unpaired p = 0.742; 95% CI: –28.2 to 6.54Paired vs neutral p = 0.015; 95% CI: 1.87 to 36.6Day6 (RT-PP)Paired vs unpaired p = 0.937; 95% CI: –26.3 to 8.46Paired vs neutral p < 0.001; 95% CI: 11.1 to 45.9Day7 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –22.3 to 12.5Paired vs neutral p < 0.001; 95% CI: 7.32 to 42.1Day8 (CR)Paired vs unpaired p = 0.976; 95% CI: –25.5 to 9.30Paired vs neutral p < 0.001; 95% CI: 7.52 to 42.3Reversal parameters:Day3 paired vs Day6 unpaired p > 0.999; 95% CI: –17.0 to 17.8Day3 paired vs Day7 unpaired p > 0.999; 95% CI: –18.4 to 16.4Day4 paired vs Day6 unpaired p > 0.999; 95% CI: –15.1 to 19.6Day4 paired vs Day7 unpaired p > 0.999; 95% CI: –16.5 to 18.2Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –17.5 to 17.3 |
Extended Data Figure 8-1F, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for Calb2-Cre/ChR2 mice under high power stimulation |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 7(M = 0, F = 7) |
Compartment p < 0.001, F(2,6) = 47.3Multiple comparisonsPaired vs unpaired p = 0.988; 95% CI: –8.15 to 8.97Paired vs neutral p < 0.001; 95% CI: 15.1 to 32.3Unpaired vs neutral p < 0.001; 95% CI: 14.7 to 31.8 |
Figure 8E, leftBehavioral analysis of NEX-Cre/ChR2 mice throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 5(M = 1, F = 4) |
Interaction: p < 0.001, F(12,48) = 4.63Day: p = 0.307, F(6,24) = 1.27Compartment: p < 0.001, F(2,8) = 76.8Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p > 0.999; 95% CI: –18.7 to 24.9Day3 (RT-PP)Paired vs unpaired p = 0.414; 95% CI: –5.70 to 37.9Paired vs neutral p < 0.001; 95% CI: 17.1 to 60.7Day4 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –17.5 to 26.1Paired vs neutral p < 0.001; 95% CI: 16.6 to 60.3Day5 (CR)Paired vs unpaired p > 0.999; 95% CI: 12.0 to 55.6Paired vs neutral p < 0.001; 95% CI: –5.03 to 38.6Day6 (RT-PP)Paired vs unpaired p = 0.020; 95% CI: –45.5 to –1.92Paired vs neutral p < 0.001; 95% CI: 15.1 to 58.7Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –51.8 to –8.16Paired vs neutral p < 0.001; 95% CI: 20.5 to 64.1Day8 (CR)Paired vs unpaired p = 0.937; 95% CI: –32.7 to 10.9Paired vs neutral p < 0.001; 95% CI: 16.3 to 59.9 |
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Reversal parameters:Day3 paired vs Day6 unpaired p = 0.049; 95% CI: 0.0239 to 43.6Day3 paired vs Day7 unpaired p = 0.016; 95% CI: 2.38 to 46.0Day4 paired vs Day6 unpaired p = 0.252; 95% CI: –4.06 to 39.5Day4 paired vs Day7 unpaired p = 0.105; 95% CI: –1.71 to 41.9Day5 paired vs Day8 unpaired p = 0.998; 95% CI: –14.0 to 29.6 |
Figure 8E, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for NEX-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 5(M = 1, F = 4) |
Compartment p < 0.001, F(2,6) = 39.7Multiple comparisonsPaired vs unpaired p = 0.013; 95% CI: 5.03 to 32.0Paired vs neutral p < 0.001; 95% CI: 25.7 to 52.6Unpaired vs neutral p = 0.008; 95% CI: 7.16 to 34.1 |
Extended Data Figure 8-1G, leftBehavioral analysis of NEX-Cre/ChR2 mice tested on high power, throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 1, F = 3) |
Interaction: p < 0.001, F(12,36) = 8.58Day: p = 0.252, F(6,18) = 1.44Compartment: p < 0.001, F(2,6) = 48.3Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.369; 95% CI: –25.0 to 3.62Day3 (RT-PP)Paired vs unpaired p = 0.358; 95% CI: –3.54 to 25.1Paired vs neutral p < 0.001; 95% CI: 16.0 to 44.6Day4 (RT-PP)Paired vs unpaired p = 0.003; 95% CI: 3.97 to 32.6Paired vs neutral p < 0.001; 95% CI: 24.9 to 53.5Day5 (CR)Paired vs unpaired p = 0.084; 95% CI: –0.819 to 27.8Paired vs neutral p < 0.001; 95% CI: 19.7 to 48.3Day6 (RT-PP)Paired vs unpaired p = 0.087; 95% CI: –27.8 to 0.877Paired vs neutral p < 0.001; 95% CI: 17.7 to 46.4Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –34.7 to –6.03Paired vs neutral p < 0.001; 95% CI: 21.8 to 50.5Day8 (CR)Paired vs unpaired p = 0.798; 95% CI: –22.5 to 6.11Paired vs neutral p < 0.001; 95% CI: 13.7 to 42.3Reversal parameters:Day3 paired vs Day6 unpaired p = 0.203; 95% CI: –2.36 to 26.3Day3 paired vs Day7 unpaired p = 0.028; 95% CI: 0.881 to 29.5Day4 paired vs Day6 unpaired p = 0.005; 95% CI: 3.12 to 31.8Day4 paired vs Day7 unpaired p < 0.001; 95% CI: 6.36 to 35.0Day5 paired vs Day8 unpaired p = 0.202; 95% CI: –2.35 to 26.3 |
Extended Data Figure 8-1G, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for NEX-Cre/ChR2 mice under high-power stimulation |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 1, F = 3) |
Compartment p < 0.001, F(2,6) = 178Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: 10.1 to 21.3Paired vs neutral p < 0.001; 95% CI: 28.8 to 40.0Unpaired vs neutral p < 0.001; 95% CI: 13.1 to 24.3 |
Extended Data Figure 8-1H, leftBehavioral analysis of bilaterally injected NEX-Cre/ChR2 mice throughout the opto-behavioral experiments |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 0, F = 4) |
Interaction: p = 0.040, F(12,36) = 2.13Day: p = 0.384, F(6,18) = 1.13Compartment: p < 0.001, F(2,6) = 43.3Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.999; 95% CI: –50.7 to 25.1Day3 (RT-PP)Paired vs unpaired p = 0.998; 95% CI: –24.6 to 51.2Paired vs neutral p = 0.017; 95% CI: 4.27 to 80.1Day4 (RT-PP)Paired vs unpaired p = 0.768; 95% CI: –15.7 to 60.2Paired vs neutral p = 0.003; 95% CI: 10.3 to 86.1Day5 (CR)Paired vs unpaired p = 0.974; 95% CI: –21.2 to 54.7Paired vs neutral p = 0.015; 95% CI: 4.63 to 80.5Day6 (RT-PP)Paired vs unpaired p > 0.999; 95% CI: –49.6 to 26.3Paired vs neutral p = 0.029; 95% CI: 2.13 to 78.0Day7 (RT-PP)Paired vs unpaired p = 0.999; 95% CI: –52.5 to 23.3Paired vs neutral p = 0.019; 95% CI: 3.69 to 79.5Day8 (CR)Paired vs unpaired p = 0.185; 95% CI: –70.1 to 5.78Paired vs neutral p < 0.001; 95% CI: 14.2 to 90.0 |
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Reversal parameters:Day3 paired vs Day6 unpaired p = 0.999; 95% CI: –25.0 to 50.8Day3 paired vs Day7 unpaired p = 0.995; 95% CI: –23.6 to 52.3Day4 paired vs Day6 unpaired p = 0.952; 95% CI: –20.0 to 55.8Day4 paired vs Day7 unpaired p = 0.999; 95% CI: –18.6 to 57.3Day5 paired vs Day8 unpaired p = 0.668; 95% CI: –14.1 to 61.8 |
Extended Data Figure 8-1H, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for bilaterally injected NEX-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 0, F = 4) |
Compartment p < 0.001, F(2,6) = 331Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: 10.1 to 20.8Paired vs neutral p < 0.001; 95% CI: 37.7 to 48.4Unpaired vs neutral p < 0.001; 95% CI: 22.2 to 32.9 |
Figure 8F, left Behavioral analysis of bilaterally injected NEX-Cre/ChR2 mice throughout the opto-behavioral experiments, tested on high power |
Normally distributed |
Two-way RM ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 0, F = 4) |
Interaction: p < 0.001, F(12,36) = 9.03Day: p = 0.310, F(6,18) = 1.29Compartment: p < 0.001, F(2,6) = 36.5Multiple comparisons (of interest)Day2 (pre-test)Paired vs unpaired p = 0.982; 95% CI: –42.9 to 17.4Day3 (RT-PP)Paired vs unpaired p = 0.349; 95% CI: –7.34 to 53.0Paired vs neutral p < 0.001; 95% CI: 20.0 to 80.3Day4 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: 14.1 to 74.4Paired vs neutral p < 0.001; 95% CI: 30.8 to 91.1Day5 (CR)Paired vs unpaired p > 0.999; 95% CI: –29.7 to 30.6Paired vs neutral p = 0.002; 95% CI: 9.24 to 69.5Day6 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –76.1 to –15.8Paired vs neutral p < 0.001; 95% CI: 28.5 to 88.8Day7 (RT-PP)Paired vs unpaired p < 0.001; 95% CI: –74.4 to –14.1Paired vs neutral p < 0.001; 95% CI: 27.0 to 87.3Day8 (CR)Paired vs unpaired p = 0.989; 95% CI: –42.4 to 17.9Paired vs neutral p = 0.006; 95% CI: 6.19 to 66.5Reversal parameters:Day3 paired vs Day6 unpaired p = 0.009; 95% CI: 5.24 to 65.5Day3 paired vs Day7 unpaired p = 0.011; 95% CI: 4.65 to 64.9Day4 paired vs Day6 unpaired p < 0.001; 95% CI: 16.0 to 76.3Day4 paired vs Day7 unpaired p < 0.001; 95% CI: 15.4 to 75.7Day5 paired vs Day8 unpaired p > 0.999; 95% CI: –20.8 to 39.5 |
Figure 8F, rightTime spent in paired, unpaired, and neutral compartments during the four RT-PP days for NEX-Cre/ChR2 mice bilaterally injected and under high-power stimulation |
Assumed normality |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 4(M = 0, F = 4) |
Compartment p < 0.001, F(2,6) = 106Multiple comparisonsPaired vs unpaired p < 0.001; 95% CI: 27.1 to 51.6Paired vs neutral p < 0.001; 95% CI: 44.5 to 69.0Unpaired vs neutral p = 0.011; 95% CI: 5.19 to 29.7 |
Extended Data Figure 8-1IiiBehavioral analysis of Vglut2-Cre throughout the NCP experiments |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 5(M = 0, F = 5) |
Interaction: p = 0.002, F(4,16) = 6.90Day: p = 0.410, F(2,8) = 1Compartment: p < 0.001, F(2,8) = 70.9Multiple comparisons (of interest)Stimulation 1Neutral vs Paired1 p = 0.009; 95% CI: –93.5 to –10.6Neutral vs Paired2 p = 0.004; 95% CI: –98.6 to –15.7Paired 1 vs Paired2 p > 0.999; 95% CI: –36.4 to 46.5Stimulation 2Neutral vs Paired1 p < 0.001; 95% CI: –113 to –29.9Neutral vs Paired2 p < 0.001; 95% CI: –112 to –29Paired 1 vs Paired2 p > 0.999; 95% CI: –42.3 to 40.6CRNeutral vs Paired1 p = 0.998; 95% CI: –49.8 to 33.1Neutral vs Paired2 p > 0.999; 95% CI: –35.5 to 47.4Paired 1 vs Paired2 p = 0.938; 95% CI: –55.7 to 27.2 |
Extended Data Figure 8-1IiiiTime spent in paired1, paired2, and neutral compartments during the two NCP days for Vglut2-Cre/ChR2 mice |
Normally distributed |
RM one-way ANOVA followed by Tukey’s multiple comparison test |
N = 5(M = 0, F = 5) |
Compartment p = 0.018, F(2,2) = 54.2Multiple comparisonsPaired1 vs Paired2 p = 0.951; 95% CI: –38.9 to 43.2Paired1 vs Neutral p = 0.023; 95% CI: –103 to –20.7Paired2 vs Neutral p = 0.021; 95% CI: –105 to –22.8 |