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. 2020 Nov 27;9:e61591. doi: 10.7554/eLife.61591

Figure 11. Dopamine neuron stimulation induces context- and history-dependent abnormal involuntary movements.

(A) Average AIMs scores during reaches for ‘ChR2 during’ rats on days 2 and 10 of ‘laser on’ sessions, and day 10 of ‘occlusion’ sessions. Also, AIMs scores during reaches for ‘EYFP’ rats on ‘laser on’ day 10. Global (Kruskal-Wallis: χ2(3)=9.31, p=2.54×10−2) and limb (χ2(3)=9.31, p=2.54×10−2) AIM scores were higher in ‘laser on’ session 10 for ChR2 rats. Axial AIM scores did not differ between groups (χ2(3)=2.83, p=0.42). * indicates p<0.05. (B) Experimental set-up for AIMs test. (C) Average global AIMs scores vs. estimated power at the fiber tip. Global AIMs increased with increasing laser power and from test day 1 to 2 in ChR2-injected rats (linear mixed model: interaction between test number and laser power: t(164) = 2.57, p=0.01). EYFP-injected rats did not display AIMs (linear mixed model: interaction between test number and laser power: t(164) = 0.00, p=1.00). ChR2-injected rats’ global AIMs scores did not differ significantly from EYFP-injected rats’ global AIMs scores on test day 1 (Contrast tests: 5 mW: t(164) = 1.57, p=0.12; 10 mW: t(164) = 1.71, p=0.09; 15 mW: t(164) = 1.45, p=0.15; 20 mW: t(164) = 1.17, p=0.24; 25 mW: t(164) = 0.98, p=0.33). Gray lines represent data from individual rats. Error bars represent s.e.m. across animals. (D) Average axial AIMs scores. ChR2: linear mixed model: interaction between test number and laser power: t(165) = 1.91, p=0.06. EYFP: t(165) = 0.00, p=1.00. ChR2-injected rats’ axial AIMs scores did not differ significantly from EYFP-injected rats’ axial AIMs scores on test day 1 (Contrast tests: 5 mW: t(165) = 1.36, p=0.18; 10 mW: t(165) = 1.46, p=0.15; 15 mW: t(165) = 1.22, p=0.23; 20 mW: t(165) = 0.97, p=0.33; 25 mW: t(165) = 0.80, p=0.43). (E) Average limb AIMs scores. A linear mixed-effects model found a significant interaction between test number and laser power in ChR2-injected rats: t(164) = 2.81, p=5.51×10−3. EYFP-injected rats did not display limb AIMs: t(164) = 0.00, p=1.00. ChR2-injected rats’ limb AIMs scores did not differ significantly from EYFP-injected rats’ limb AIMs scores on test day 1 (Contrast tests: 5 mW: t(164) = 1.42, p=0.16; 10 mW: t(164) = 1.55, p=0.12; 15 mW: t(164) = 1.33, p=0.19; 20 mW: t(164) = 1.08, p=0.28; 25 mW: t(164) = 0.91, p=0.37). (F) Difference between average number of contralateral and ipsilateral (relative to hemisphere implanted with optical fiber) rotations. A positive score indicates a bias toward contralateral spins and a negative score indicates a bias towards ipsilateral spins. ChR2-injected rats did not increase the number of contralateral spins between test 1 and test 2, nor did laser power affect rotational behavior. Linear mixed model: interaction between test number and laser power: t(164) = −0.39, p=0.69. EYFP-injected rats did not show a bias in either direction with laser stimulation: t(164) = 0.10, p=0.92. (*p<0.05, **p<0.01 for ChR2-injected rats). ChR2 rats had a stronger bias toward contralateral spins compared to EYFP rats at 5 mW (contrast tests: t(164) = 2.57, p=0.01), 10 (t(164) = 3.44, p=7.37×10−4), 15 (t(164) = 3.38, p=9.19×10−4), 20 mW (t(164) = 3.05, p=2.69×10−3), and 25 mW (t(164) = 2.77, p=6.29×10−3) on test day 1. ChR2 rats in panels C-F include rats from ‘ChR2 during’ (n = 5) and ‘ChR2 between’ (n = 7) groups. Figure 11—figure supplement 1 shows the relationship between AIMs scores in the cylinder and reach success rates for individual rats.

Figure 11—source data 1. A .mat file containing number of rotations to the left (leftSpin) and right (rightSpin), axial AIMs scores (axialAmplitude and axialBasis), and limb AIMs scores (limbAmplitude and limbBasic) from AIMs tests 1 and 2.
Field 1 = ChR2 During test 1; Field 2 = ChR2 Between test 1; Field 3 = EYFP test 1; Field 4 = ChR2 During test 2; Field 5 = ChR2 Between test 2; Field 6 = EYFP test 2.
Figure 11—source data 2. A .mat file containing limb and axial amplitude scores for randomly selected skilled reaching trials.
Data is scores for each trial per rat.

Figure 11.

Figure 11—figure supplement 1. Dyskinesias in the second AIMs test do not consistently predict changes in reach success rate.

Figure 11—figure supplement 1.

(A) For ‘ChR2 During’ rats, global AIMs scores from AIMs test 2 (at the 20 mW power) are plotted against the change in success rate from the last two retraining sessions to ‘laser on’ day 10. Negative numbers indicate a decrease in reach success rate. Even rats with no dyskinesias in the cylinder had a marked reduction in success rate. (B) For ‘ChR2 Between’ rats, global AIMs scores from AIMs test 2 (at the 20 mW power) are plotted against the change in success rate from the last 2 ‘occlusion’ sessions to ‘laser on during’ session 1. Note that rats with dyskinesias in the cylinder had no or mild decreases in success rate on the first day of ‘during reach’ stimulation.
Figure 11—figure supplement 1—source data 1. A.mat file containing axial AIMs scores (axialAmplitude and axialBasis) and limb AIMs scores (limbAmplitude and limbBasic) from AIMs tests 1 and 2.
Field 1 = ChR2 During test 1; Field 2 = ChR2 Between test 1; Field 3 = EYFP test 1; Field 4 = ChR2 During test 2; Field 5 = ChR2 Between test 2; Field 6 = EYFP test 2.
Figure 11—figure supplement 1—source data 2. A .mat file containing first reach success rate data (firstReachSuccess) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
Figure 11—figure supplement 1—source data 3. A .mat file containing containing first reach success rate data (firstReachSuccess) for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
Data is average per session for each rat.