Precisely timed dopamine signals establish distinct kinematic representations of skilled movements
- Neuroscience Graduate Program, University of Michigan, United States
- Department of Neurology, University of Michigan, United States
- Department of Biomedical Engineering, University of Michigan, United States
- Parkinson Disease Foundation Research Center of Excellence, University of Michigan, United States
- Department of Neurology, VA Ann Arbor Health System, United States
Figures
Figure 1 with 3 supplements
Experimental framework.
(A) Timeline for a single experiment. AIMs Test – Abnormal Involuntary Movement testing (see ‘Dopamine neuron stimulation induces context- and history-dependent abnormal involuntary movements’). The ‘ChR2 between’ group also received ‘during reach’ stimulation after ‘occlusion’ sessions (see Figure 11). (B) Light was physically occluded from entering the brain by obstructing the connection between the optical fiber and patch cable during ‘occlusion’ sessions. (C) Rats were assigned to one of five groups based on virus injected and timing of optogenetic manipulation. n is the number of rats included in the analysis for each group (see Materials and methods). Dot colors correspond with the color used to represent each group in subsequent figures. (D) A single skilled reaching trial. 1 – rat breaks IR beam at the back of the chamber to request a sugar pellet (‘beam break’). 2 – Real-time analysis detects the paw breaching the reaching slot to trigger 300 fps video from 1 s before to 3.33 s after the trigger event (‘video trigger’). 3 – 2 s after the trigger event, the pellet delivery rod resets and the rat can initiate a new trial (‘intertrial interval’). Optogenetic manipulations occurred either during reaching (beam break to 3 s after ‘video trigger’) or between reaches (beginning 4 s after ‘video trigger’ and lasting 5 s). Figure 1—figure supplement 1 shows the distribution of the duration of ‘during reach’ laser-on epochs. (E) Double-floxed ChR2-EYFP, Arch-EYFP, or control EYFP constructs were injected bilaterally into SNc. (F) Immunohistochemistry against EYFP showing expression of a fused ChR2-EYFP construct in the nigrostriatal pathway. Optical fibers (arrow) were implanted over SNc contralateral to the rat’s preferred reaching paw. Estimated locations of all fiber tips are shown in Figure 1—figure supplement 2. Representative immunohistochemistry images from each group are shown in Figure 1—figure supplement 3. Scale bar = 1 mm.
Figure 1—figure supplement 1
The duration of ‘during reach’ and ‘between reach’ stimulation is closely matched.
(A) Distribution of the duration of ‘during reach’ stimulation for all ‘ChR2 during’ rats. The median duration of ‘during reach’ stimulation was 5.37 s compared to 5 s for ‘between reach’ stimulation (sign test: Z = 18.96, p=1.89×10−80). (B) Same as (A) for each rat individually. (C) Distribution of the duration of ‘during reach’ inhibition for all ‘Arch during’ rats. The median duration of ‘during reach’ inhibition was 5.75 s compared to 5 s for ‘between’ reach inhibition (sign test: Z = 25.46, p=2.53×10−143). (D) Same as (C) for each rat individually. Dashed lines represent median ‘during reach’ durations. Solid lines at 5 s represent duration of ‘between reach’ stimulation for comparison.
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Figure 1—figure supplement 1—source data 1
A .mat file containing the durations of each ‘laser on’ bout in the 10 ‘laser on’ sessions for each rat from ‘ChR2 During’, ‘ChR2 Between’, ‘Arch During’, and ‘Arch Between’ groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig1-figsupp1-data1-v2.mat
Figure 1—figure supplement 2
Optical fiber locations.
(A) Circles indicate optical fiber tip locations in rats analyzed from each group superimposed on coronal rat brain atlas images (Paxinos and Watson, 1998). X’s indicate optical fiber tip locations of rats excluded from the analysis due to either fiber misplacement or lack of opsin expression (see Materials and methods). (B) Optical fiber tip locations superimposed on sagittal rat brain atlas images. (C) Three-dimensinal optical fiber tip locations for each group. Small dots represent individual rats. Large dots represent average locations for each group. A-P and M-L coordinates are with respect to bregma; D-V coordinates are with respect to the brain surface. (D) Three-dimensional A-P, M-L, and D-V coordinates for each fiber tip. There were no significant differences in fiber tip locations between groups along any axes (one-way ANOVAs: A-P: F(4, 25)=0.28, p=0.89; M-L: F(4, 25)=0.38, p=0.82; D-V: F(4, 25)=0.95, p=0.45). Gray dots represent locations for individual rats.
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Figure 1—figure supplement 2—source data 1
A .xlsx file containing the estimated fiber tip locations for each rat in all groups.
Virus 1 = ‘ChR2 During’; Virus 2 = ‘ChR2 Between’; Virus 3 = ‘Arch During’; Virus 4 = ‘Arch Between’; Virus 5 = ‘EYFP’.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig1-figsupp2-data1-v2.xlsx
Figure 1—figure supplement 3
Representative immunohistochemistry against EYFP showing expression of fused opsin-EYFP constructs in the nigrostriatal pathway for all groups.
Images on the left (‘Analyzed Rats’) show examples of immunohistochemistry from rats that were included in analyses for each group. Images on the right (‘Excluded Rats’) show examples of immunohistochemistry from rats that were excluded from analyses for each group. Reasons for exclusion from top to bottom: ChR2 During – optical fiber tip ventral to SNc and weak opsin expression; ChR2 Between – optical fiber tip ventral to SNc; Arch During – optical fiber tip rostral to SNc; EYFP – optical fiber tip rostral to SNc. Scale bar = 1 mm.
Figure 2 with 2 supplements
Dopamine neuron stimulation during reaches gradually impairs skilled reaching performance.
(A) Average number of trials per session over last two ‘retraining’ sessions for each group. Black dots represent individual rats. Baseline number of reaches performed did not differ between groups. Kruskal-Wallis Test: χ2(4)=3.94, p=0.41. (B) Average number of trials per session divided by the baseline number of trials for ‘during reach’ stimulation. Gray lines represent individual rats. Linear mixed model: effect of laser: t(79) = 0.932, p=0.35; interaction between laser and session: t(584) = −0.99, p=0.32. (C) Same as (B) for control rats injected with an EYFP-only construct. Linear mixed model: effect of laser: t(79) = −0.90, p=0.37; interaction between laser and session: t(584) = 1.20, p=0.23. (D) Average first attempt success rate over the last two ‘retraining’ sessions for each group. Black dots represent individual rats. Baseline success rate did not differ between groups. Kruskal-Wallis Test: χ2(4)=6.18, p=0.19. (E) Average first attempt success rate divided by baseline success rate for ‘during reach’ stimulation. Linear mixed model: effect of laser: t(133) = −3.76, p=2.51×10−4; interaction between laser and session: t(584) = −1.50, p=0.13. (F) Same as (E) for control rats injected with an EYFP-only construct. Linear mixed model: effect of laser: t(134) = 0.63, p=0.53; interaction between laser and session: t(584) = −0.42, p=0.67. (G) Moving average of success rate within individual sessions in the last retraining session, first 5 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. Unlike panels E and F, these are not normalized to retraining sessions because they are within-session moving averages. Black bars represent statistically significant differences between groups (Wilcoxon rank sum test, p<0.01). ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Shaded colored areas in (G) and error bars in B-C and E-F represent standard errors of the mean (s.e.m). Data for individual rats are shown in Figure 2—figure supplement 1. Figure 2—figure supplement 2 shows additional performance measures for ‘during reach’ ChR2 activation and EYFP control rats (‘any reach’ success rates, number of attempts per trial, and breakdown of reach outcomes across sessions). *** Indicates p<0.001 for the laser term in the linear mixed model in panel E.
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Figure 2—source data 1
A .mat file containing number of trials (num_trials) and first reach success rate (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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-data1-v2.mat
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Figure 2—source data 2
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-data2-v2.mat
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Figure 2—source data 3
Statistics.
A.xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between ChR2 During and EYFP group averages in Figure 2G.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-data3-v2.xlsx
Figure 2—figure supplement 1
Moving average of success rate within individual sessions (ChR2 During and EYFP) for each rat.
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 2—figure supplement 1—source data 1
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-figsupp1-data1-v2.mat
Figure 2—figure supplement 2
Additional task performance measures for ‘during reach’ stimulation and EYFP controls.
(A) ‘Any reach’ success rate for ‘during reach’ ChR2 stimulation. Gray lines represent individual rats. Linear mixed model: effect of laser: t(144) = −3.21, p=1.66×10−3; interaction between laser and session: t(585) = −1.357, p=0.18. (B) Same as (A) for EYFP control rats. Linear mixed model: effect of laser: t(145) = 0.32, p=0.75; interaction between laser and session: t(585) = −0.22, p=0.83. (C) Number of reach attempts per trial for ‘during reach’ ChR2 stimulation. Linear mixed model: effect of laser: t(67) = 3.49, p=8.57×10−4; interaction between laser and session: t(585) = 0.37, p=0.72. (D) Same as (C) for EYFP control rats. Linear mixed model: effect of laser: t(67) = −0.05, p=0.96; interaction between laser and session: t(585) = 0.17, p=0.87. (E) Breakdown of trial outcomes by session for ‘during reach’ ChR2 stimulation (left) and EYFP control rats (right) (see Materials and methods, Number of trials and success rate for definitions of the outcomes). In addition to decreasing first reach success outcomes (Linear mixed model: effect of laser: t(106) = −3.95, p=1.43×10−4; interaction between laser and session: t(587) = −1.75, p=0.08), ChR2 stimulation during reaches increased the number of trials where the pellet remained on the pedestal (Linear mixed model: effect of laser: t(46) = 1.76, p=0.09; interaction between laser and session: t(612) = 2.09, p=0.04), the rat used its ipsilateral paw to reach (Linear mixed model: effect of laser: t(58) = −1.77, p=0.08; interaction between laser and session: t(612) = 5.90, p=5.87×10−9), and the paw was through the slot at video start (i.e. video was triggered too late, linear mixed model: effect of laser: t(272) = 0.64, p=0.52; interaction between laser and session: t(587) = 2.07, p=0.04). All other outcomes were consistent across sessions. * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001 in the linear mixed model in panels A, C, and E. The color of the * in panel E corresponds to the group with statistical significance. Blue and pink boxes in Panel E highlight ‘Laser On’ sessions.
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Figure 2—figure supplement 2—source data 1
A .mat file containing any reach success rate (anyReachSuccess) and number of reach attempts (mean_num_reaches) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-figsupp2-data1-v2.mat
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Figure 2—figure supplement 2—source data 2
A .mat file containing percentage of trials that were each outcome type for each session for each rat (fullOutcomePercent).
The field ‘fullOutcomeNames’ lists the names of each outcome type (see Materials and methods for descriptions). The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-figsupp2-data2-v2.mat
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Figure 2—figure supplement 2—source data 3
Statistics.
A .xlsx file containing the statistical output of linear mixed-effects models run for each outcome type (Figure 2—figure supplement 2E). Statistics are reported for effects of laser and interactions between laser and session number.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig2-figsupp2-data3-v2.xlsx
Figure 3 with 2 supplements
Dopamine neuron stimulation between reaches does not affect skilled reaching performance.
(A) Average number of trials per session divided by the baseline number of trials for ‘between reach’ stimulation. Gray lines represent individual rats. Linear mixed model: effect of laser: t(79) = 1.13, p=0.26; interaction between laser and session: t(584) = −0.64, p=0.52. (B) Average first attempt success rate divided by baseline success rate for ‘between reach’ stimulation. Linear mixed model: effect of laser: t(133) = −0.29, p=0.78; interaction between laser and session: t(584) = −0.94, p=0.35. (C) Moving average of success rate within individual sessions in the last retraining session, first 5 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. ‘During reach’ data from Figure 2 are shown for comparison. Unlike panel B, these are not normalized to retraining sessions because they are within-session moving averages. Black bars represent trials with a statistically significant difference between groups (Wilcoxon rank sum text, p<0.01). Data for individual rats are shown in Figure 3—figure supplement 1. Figure 3—figure supplement 2 shows additional performance measures for ‘between reach’ ChR2 activation (‘any reach’ success rates, number of attempts per trial, and breakdown of reach outcomes across sessions). Shaded colored areas in C and error bars in A-B represent s.e.m.
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Figure 3—source data 1
A .mat file containing number of trials (num_trials) and first reach success rate (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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-data1-v2.mat
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Figure 3—source data 2
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-data2-v2.mat
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Figure 3—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between ChR2 During and ChR2 Between group averages in Figure 3C.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-data3-v2.xlsx
Figure 3—figure supplement 1
Individual rat data for moving average of success rate across trials within individual sessions (‘ChR2 Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 3—figure supplement 1—source data 1
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-figsupp1-data1-v2.mat
Figure 3—figure supplement 2
Additional task performance measures for ‘between reach’ ChR2 stimulation.
(A) ‘Any reach’ success rate. Linear mixed model: effect of laser: t(144) = −0.31, p=0.76; interaction between laser and session: t(585) = −0.55, p=0.58. (B) Number of reach attempts per trial. Linear mixed model: effect of laser: t(67) = 0.46, p=0.64; interaction between laser and session: t(585) = 0.29, p=0.77. (C) Breakdown of trial outcomes by session (see Materials and methods, Number of trials and success rate for definitions of the outcomes). There was a significant increase in ‘no pellet’ (linear mixed model: effect of laser: t(607) = 2.85, p=4.45×10−3; interaction between laser and session: t(612) = −2.85, p=4.59×10−3) and ‘laser error’ (linear mixed model: effect of laser: t(389) = −0.94, p=0.35; interaction between laser and sessions: t(612) = 2.15, p=0.03) trials during ‘laser on’ sessions. All other outcomes were consistent across sessions. * indicates p<0.05 and ** indicates p<0.01 in the linear mixed model in panel C. Purple box in Panel E highlights ‘Laser On’ sessions.
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Figure 3—figure supplement 2—source data 1
A .mat file containing any reach success rate (anyReachSuccess) and number of reach attempts (mean_num_reaches) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-figsupp2-data1-v2.mat
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Figure 3—figure supplement 2—source data 2
A .mat file containing percentage of trials that were each outcome type for each session for each rat (fullOutcomePercent).
The field ‘fullOutcomeNames’ lists the names of each outcome type (see Materials and methods for descriptions). The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-figsupp2-data2-v2.mat
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Figure 3—figure supplement 2—source data 3
Statistics.
A .xlsx file containing the statistical output of linear mixed-effects models run for each outcome type (Figure 3—figure supplement 2C). Statistics are reported for effects of laser and interactions between laser and session number.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig3-figsupp2-data3-v2.xlsx
Figure 4 with 3 supplements
Dopamine neuron inhibition during reaches decreases the number of reaches performed but does not impair reach accuracy.
(A) Average number of trials per session divided by the baseline number of trials for ‘during reach’ inhibition. Gray lines represent individual rats. Linear mixed model: effect of laser: t(80) = −0.21, p=0.84; interaction between laser and session: t(584) = −2.64, p=8.47×10-3. (B) Same as (A) for ‘between reach’ inhibition. Linear mixed model: effect of laser: t(80) = 0.93, p=0.36; interaction between laser and session: t(584) = −1.52, p=0.13. (C) Average first attempt success rate divided by baseline success rate for ‘during reach’ inhibition. Linear mixed model: effect of laser: t(133) = 0.59, p=0.56; interaction between laser and session: t(584) = −0.40, p=0.69. (D) Same as (C) for ‘between reach’ inhibition. Linear mixed model: effect of laser: t(133) = −0.64, p=0.52; interaction between laser and session: t(584) = 0.10, p=0.92. (E) Moving average of success rate across trials within individual sessions in the last retraining session, first 5 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. Unlike panels C and D, these are not normalized to retraining sessions because they are within-session moving averages. Black bars represent statistically significant differences between groups (Wilcoxon rank sum test, p<0.01). ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Figure 4—figure supplement 3 shows additional performance measures for ‘during reach’ and ‘between reach’ Arch activation (‘any reach’ success rates, number of attempts per trial, and breakdown of reach outcomes across sessions). Shaded colored areas in (E) and error bars in A-D represent s.e.m. Moving average of success rate within sessions for Arch Between rats is shown in Figure 4—figure supplement 1. Data for individual Arch During and Arch Between rats are shown in Figure 4—figure supplement 2. ** indicates p<0.01 for the laser-session interaction term in panel A.
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Figure 4—source data 1
A .mat file containing number of trials (num_trials) and first reach success rate (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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-data1-v2.mat
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Figure 4—source data 2
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-data2-v2.mat
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Figure 4—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between Arch During and EYFP group averages in Figure 4E.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-data3-v2.xlsx
Figure 4—figure supplement 1
Moving average of success rate across trials within individual sessions in Arch-injected rats receiving dopamine neuron inhibition between reaches.
‘During reach’ data from Figure 4 are shown for comparison. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 4—figure supplement 1—source data 1
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp1-data1-v2.mat
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Figure 4—figure supplement 1—source data 2
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between Arch During and Arch Between group averages in Figure 4—figure supplement 1.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp1-data2-v2.xlsx
Figure 4—figure supplement 2
Individual rat data for moving average of success rate across trials within individual sessions (‘Arch During’ and ‘Arch Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 4—figure supplement 2—source data 1
A .mat file containing first reach success rate averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp2-data1-v2.mat
Figure 4—figure supplement 3
Additional task performance measures for ‘during reach’ and ‘between reach’ Arch activation.
(A) ‘Any reach’ success rate for ‘during reach’ Arch activation. Linear mixed model: effect of laser: t(144) = 0.32, p=0.75; interaction between laser and session: t(585) = −0.13, p=0.89. (B) Same as (A) for ‘between reach’ Arch activation. Linear mixed model: effect of laser: t(144) = −0.15, p=0.88; interaction between laser and session: t(585) = −0.41, p=0.69. (C) Number of reach attempts per trial for ‘during reach’ Arch activation. Linear mixed model: effect of laser: t(67) = −0.73, p=0.47; interaction between laser and session: t(585) = −0.42, p=0.68. (D) Same as (C) for ‘between reach’ Arch activation. Linear mixed model: effect of laser: t(67) = 0.36, p=0.72; interaction between laser and session: t(585) = −0.46, p=0.65. (E) Breakdown of trial outcomes by session for ‘during reach’ Arch activation (left) and ‘between reach’ Arch activation (right) (see Materials and methods, Number of trials and success rate for definitions of the outcomes). All outcomes remained consistent across sessions for both groups. Green and orange boxes highlight ‘Laser On’ sessions in Panel E.
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Figure 4—figure supplement 3—source data 1
A .mat file containing any reach success rate (anyReachSuccess) and number of reach attempts (mean_num_reaches) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp3-data1-v2.mat
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Figure 4—figure supplement 3—source data 2
A .mat file containing percentage of trials that were each outcome type for each session for each rat (fullOutcomePercent).
The field ‘fullOutcomeNames’ lists the names of each outcome type (see Materials and methods for descriptions). The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp3-data2-v2.mat
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Figure 4—figure supplement 3—source data 3
Statistics.
A. xlsx file containing the statistical output of linear mixed-effects models run for each outcome type (Figure 4—figure supplement 3E). Statistics are reported for effects of laser and interactions between laser and session number.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig4-figsupp3-data3-v2.xlsx
Figure 5
Paw and digit tracking with Deeplabcut.
(A) Deeplabcut identification of digits, paw dorsum, nose, and pellet in individual video frames (side mirror and direct views). X, Y, and Z coordinates are in reference to the pellet. (B) Reach extent (zdigit2) is the z-coordinate of the tip of the second digit. The end of a reach is defined as the moment zdigit2 begins to decrease (the digit tip moves back toward the box). Inset – mirror view of the palmar surface of the paw (C) Grasp aperture (a) is the Euclidian distance between the first and fourth digit tips. (D) Paw orientation is the angle (θ) between a line connecting the first and fourth digit tips and the floor. (E) Example three-dimensional reconstruction of reaching trajectories from a single ‘retraining’ session. Colored lines represent individual trials and black lines represent average trajectories of the paw dorsum and digit tips. Sugar pellet (black dot) is at (0,0,0).
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Figure 5—source data 1
A .mat file containing paw trajectories (reachData.pd_trajectory) and individual digit trajectories (reachData.dig_trajectory) for each trial in a single ‘retraining’ session for a ‘ChR2 During’ rat.
X, Y, and Z coordinates are provided for each trajectory.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig5-data1-v2.mat
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Figure 5—source data 2
A .mat file containing average paw (ratSummary.mean_pd_trajectory) and digit (ratSummary.mean_dig_trajectories) trajectories across all 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’) for the same rat as in Figure 5—source data 1.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig5-data2-v2.mat
Figure 6 with 8 supplements
Dopamine neuron stimulation induces progressive changes in reach-to-grasp kinematics.
(A) The average maximum reach extent progressively decreased across sessions with ‘during reach’ stimulation. Linear mixed model: effect of laser: t(62) = 1.70, p=0.09; interaction between laser and session: t(585) = 6.88, p=1.59×10−11. Average maximum reach extent returned to baseline within the first ‘occlusion’ session. Contrast testing (‘retraining’ session 10 vs. ‘occlusion’ session 1): t(585) = 1.62, p=0.11. (B) Same as (A) for ‘between reach’ stimulation. Linear mixed model: effect of laser: t(62) = 0.02, p=0.99; interaction between laser and session: t(585) = −0.43, p=0.67. (C) Same as (A) and (B) for ‘during reach’ illumination in control EYFP-injected rats. Linear mixed model: effect of laser: t(62) = 0.10, p=0.92; interaction between laser and session: t(585) = −0.68, p=0.50. Figure 6—figure supplement 1 shows the relationship between reach extent and fiber tip location for these groups. (D) Moving average of maximum reach extent within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. Black bars represent trials with a statistically significant difference between groups (Wilcoxon rank sum test, p<0.01). (E) Average grasp aperture at reach end for ‘during reach’ stimulation. Linear mixed model: effect of laser: t(48) = −1.34, p=0.19; interaction between laser and session: t(585) = −2.19, p=0.03. Average aperture returned to baseline within the first ‘occlusion’ session. Contrast testing (‘retraining’ session 10 vs. ‘occlusion’ session 1): t(585) = −0.87, p=0.38. (F) Moving average of aperture at reach end within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (G) Same as (E) for paw orientation. Linear mixed model: effect of laser: t(74) = −2.52, p=0.01; interaction between laser and session: t(585) = 0.19, p=0.85. Average angle returned to baseline within the first ‘occlusion’ session. Contrast testing (‘retraining’ session 10 vs. ‘occlusion’ session 1): t(585) = 1.64, p=0.10. (H) Moving average of paw angle at reach end across trials in the last (10th) ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (I) Same as (E) and (G) for maximum reach velocity. Linear mixed model: effect of laser: t(49) = −0.45, p=0.65; interaction between laser and session: t(585) = −2.45, p=0.01. Average velocity returned to baseline within the first ‘occlusion’ session. Contrast testing (‘retraining’ session 10 vs. ‘occlusion’ session 1): t(585) = −1.64, p=0.10. (J) Moving average of maximum reach velocity within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Shaded colored areas in D, F, H, J and error bars in A, B, C, E, I represent s.e.m. Similar data for ChR2 Between rats are shown in Figure 6—figure supplement 2. Individual rat data are shown in Figure 6—figure supplements 3–6. Figure 6—figure supplement 7 compares kinematic measures (final zdigit2, aperture, paw orientation, and maximum reach velocity) between successful and unsuccessful reaches for ChR2 during, ChR2 between, and EYFP rats. Figure 6—figure supplement 8 shows success rate and kinematic measures as a function of final zdigit2 for ChR2 during, ChR2 between, and EYFP rats. * indicates p<0.05 for the laser or laser-session interaction terms in panels E, G, I. *** indicates p<1.0×10−10 for the laser-session interaction term in panel A.
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Figure 6—source data 1
A .mat file containing maximum reach extent of digit2 (mean_dig2_endPt), aperture at reach end (mean_end_aperture), paw orientation at reach end (mean_end_orientations), and mean paw velocity (mean_pd_v) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-data1-v2.mat
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Figure 6—source data 2
A .mat file containing digit2 endpoint (digEnd), aperture at reach end (aperture), orientation at reach end (orientation), and velocity (velocity) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-data2-v2.mat
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Figure 6—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between ChR2 During and EYFP group averages in Figures 6D, F, H and J.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-data3-v2.xlsx
Figure 6—figure supplement 1
Maximum reach extent on laser day 10 as a function of anterior-posterior, medial-lateral, and dorsal-ventral fiber tip coordinates referenced to bregma (A–P and M–L) or brain surface (D–V).
The same symbol represents the same rat across panels within each group. r and p values are for linear regressions fit to each plot. Bold r and p-values indicate p<0.05. (A) ‘ChR2 during’ group. Note posteromedial sites tended to have stronger effects, although this may have been driven by one subject. (B) ‘ChR2 between’ group. (C) ‘EYFP’ group.
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Figure 6—figure supplement 1—source data 1
A .mat file containing digit2 endpoints (mean_dig2_endPt) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp1-data1-v2.mat
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Figure 6—figure supplement 1—source data 2
A .xlsx file containing the estimated fiber tip locations for each rat in all groups.
Virus 1 = 'ChR2 During'; Virus 2 = 'ChR2 Between'; Virus 3 = 'Arch During'; Virus 4 = 'Arch Between'; Virus 5 = 'EYFP'.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp1-data2-v2.xlsx
Figure 6—figure supplement 2
Reach-to-grasp kinematics do not change in EYFP control rats or ChR2-injected rats receiving between reach stimulation.
(A) Average grasp aperture in EYFP control rats. Gray lines represent individual rats. Linear mixed model: effect of laser: t(48) = −0.16, p=0.88; interaction between laser and session: t(585) = −1.14, p=0.26. (B) Same as (A) but for paw orientation. Linear mixed model: effect of laser: t(75) = −0.65, p=0.52; interaction between laser and session: t(585) = 0.47, p=0.64. (C) Same as (A) and (B) but for maximum reach velocity. Linear mixed model: effect of laser: t(49) = −0.23, p=0.82; interaction between laser and session: t(585) = 0.72, p=0.47. (D) Moving average of maximum reach extent for ‘between reach’ stimulation within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. Black bars represent trials with a statistically significant difference between groups (Wilcoxon rank sum test, p<0.01). Data for ‘during reach’ stimulation from Figure 6D are shown for comparison. (E) Average grasp aperture for ‘between reach’ stimulation. Linear mixed model: effect of laser: t(48) = −0.60, p=0.55; interaction between laser and session: t(585) = 2.59, p=9.76×10−3. (F) Moving average of aperture at grasp end within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. Black bars represent trials with a statistically significant difference between groups (Wilcoxon rank sum test, p<0.01). (G) Same as (E) for paw orientation. Linear mixed model: effect of laser: t(74) = −0.67, p=0.51; interaction between laser and session: t(585) = 1.85, p=0.06. (H) Moving average of paw angle at grasp end within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. Black bars represent trials with a statistically significant difference between groups (Wilcoxon rank sum test, p<0.01). (I) Same as (E) and (G) for maximum reach velocity. Linear mixed model: effect of laser: t(49) = 0.17, p=0.87; interaction between laser and session: t(585) = −0.43, p=0.67. (J) Moving average of maximum reach velocity within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Shaded colored areas in D, F, H, J and error bars in A, B, C, E, G, I represent s.e.m. ** indicates p<0.01 for the laser-session interaction term in panel E.
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Figure 6—figure supplement 2—source data 1
A .mat file containing aperture at reach end (mean_end_aperture), paw orientation at reach end (mean_end_orientations), and mean paw velocity (mean_pd_v) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp2-data1-v2.mat
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Figure 6—figure supplement 2—source data 2
A .xlsx file containing the estimated fiber tip locations for each rat in all groups.
Virus 1 = ‘ChR2 During’; Virus 2 = ‘ChR2 Between’; Virus 3 = ‘Arch During’; Virus 4 = ‘Arch Between’; Virus 5 = ‘EYFP’.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp2-data2-v2.mat
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Figure 6—figure supplement 2—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between ChR2 During and ChR2 Between group averages in Figure 6—figure supplement 2 panels D, F, H, and J.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp2-data3-v2.xlsx
Figure 6—figure supplement 3
Individual rat data for moving average of maximum reach extent across trials within individual sessions (‘ChR2 During’, ‘ChR2 Between’ and ‘EYFP’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 6—figure supplement 3—source data 1
A .mat file containing digit2 endpoint (digEnd) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp3-data1-v2.mat
Figure 6—figure supplement 4
Individual rat data for moving average of grasp aperture across trials within individual sessions (‘ChR2 During’, ‘ChR2 Between’ and ‘EYFP’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 6—figure supplement 4—source data 1
A .mat file containing aperture at reach end averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp4-data1-v2.mat
Figure 6—figure supplement 5
Individual rat data for moving average of paw angle across trials within individual sessions (‘ChR2 During’, ‘ChR2 Between’ and ‘EYFP’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 6—figure supplement 5—source data 1
A .mat file containing orientation at reach end averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp5-data1-v2.mat
Figure 6—figure supplement 6
Individual rat data for moving average of maximum reach velocity across trials within individual sessions (‘ChR2 During’, ‘ChR2 Between’ and ‘EYFP’).
Each colored line represents the same rat across panels.
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Figure 6—figure supplement 6—source data 1
A .mat file containing reach velocity averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp6-data1-v2.mat
Figure 6—figure supplement 7
Kinematic measures separated by reach success or failure for ChR2 During (left column), ChR2 Between (middle column), and EYFP (right column) groups.
(A) Average maximum reach extent. Maximum reach extent was significantly shorter for failed reaches than successful reaches with stimulation during reaches (linear mixed model: interaction between laser and outcome: t(1188) = 0.54, p=0.59; interaction between session, laser, and outcome: t(1189) = −3.20, p=1.41×10−3). There was no significant difference in maximum reach extent by outcome during ‘Laser On’ sessions for ChR2 between (interaction between laser and outcome: t(1188) = 0.70, p=0.48; interaction between session, laser, and outcome: t(1188) = 0.26, p=0.79) or EYFP groups (interaction between laser and outcome: t(1188) = −0.91, p=0.36; interaction between session, laser, and outcome: t(1188) = 0.74, p=0.46). (B) Same as (A) for aperture at the end of the reach. Aperture was significantly smaller for failed reaches than successful reaches with stimulation during reaches (interaction between laser and outcome: t(1166) = 0.04, p=0.97; interaction between session, laser, and outcome: t(1176) = 2.05, p=0.04). There was no significant difference in aperture by outcome during ‘Laser On’ sessions for ChR2 between (interaction between laser and outcome: t(1163) = −0.71, p=0.48; interaction between session, laser, and outcome: t(1164) = 0.30, p=0.77) or EYFP groups (interaction between laser and outcome: t(1163) = 1.08, p=0.28; interaction between session, laser, and outcome: t(1163) = −0.55, p=0.58). (C) Same as (A) for reach orientation at the end of the reach. There was no significant difference in paw orientation by outcome during ‘Laser On’ sessions for ChR2 During (interaction between laser and outcome: t(1185) = 1.81, p=0.07; interaction between session, laser, and outcome: t(1190) = −1.46, p=0.14), ChR2 Between (interaction between laser and outcome: t(1184) = 1.24, p=0.21; interaction between session, laser, and outcome: t(1185) = −1.19, p=0.23), or EYFP groups (interaction between laser and outcome: t(1184) = −0.80, p=0.42; interaction between session, laser, and outcome: t(1184) = 0.92, p=0.36). (D) Same as (A) for maximum reach velocity. Velocity was significantly smaller for failed reaches than successful reaches with stimulation during reaches (interaction between laser and outcome: t(1188) = 0.04, p=0.97; interaction between session, laser, and outcome: t(1191) = 2.22, p=0.03). There was no significant difference in velocity by outcome during ‘Laser On’ sessions for ChR2 between (interaction between laser and outcome: t(1187) = 0.48, p=0.63; interaction between session, laser, and outcome: t(1187) = −0.83, p=0.41) or EYFP groups (interaction between laser and outcome: t(1187) = −0.66, p=0.51; interaction between session, laser, and outcome: t(1187) = 0.93, p=0.35). * indicates p<0.05 and ** indicates p<0.01 in the linear mixed model.
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Figure 6—figure supplement 7—source data 1
A .mat file containing digit2 endpoint (mean_dig2_endPt_z), aperture at reach end (mean_end_aperture), orientation at reach end (mean_end_orientation), and reach velocity (mean_pd_v) separated by trial outcome.
Each column is a different outcome type, which are specified in the field ‘outcomeNames’ (e.g. column two is first reach success).
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp7-data1-v2.mat
Figure 6—figure supplement 8
Differences between reaches matched for reach extent in the ChR2 during (left column), ChR2 between (middle column), and EYFP (right column) groups.
(A) Average number of trials per session with different reach extents in each group. Note skew towards shorter reaches in ChR2 during, ‘laser on’ sessions. Only reaches past the pellet were included in this analysis since shorter reaches cannot be successful. (B) Average success rate as a function of reach extent across groups. Even for extent-matched reaches, ChR2 during rats are less successful during ‘laser on’ compared to ‘occlusion’ sessions. (C) Same as (B) for aperture at reach end. (D) Same as (B) and (C) for paw orientation at reach end. * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001 for comparisons between laser on and retraining (paired t-tests). # indicates p<0.05, ## indicates p<0.01, and ### indicates p<0.001 for comparisons between laser on and occluded (paired t-tests).
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Figure 6—figure supplement 8—source data 1
A .mat file containing digit2 endpoint (digEnd), aperture at reach end (aperture), orientation at reach end (orient), and trial outcomes (outcome) for all trials across all sessions for each rat.
The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp8-data1-v2.mat
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Figure 6—figure supplement 8—source data 2
Statistics.
A .xlsx file containing statistical output for paired t-test comparisons between ‘laser on’ and ‘retraining’ sessions and between ‘laser on’ and ‘occluded’ sessions for ChR2 During, ChR2 Between, and EYFP groups. ‘Z Block’ is the 10 groups of trials stratified by their maximum zdigit2 extent.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig6-figsupp8-data2-v2.xlsx
Figure 7 with 8 supplements
Dopamine neuron inhibition induces subtle changes in reach-to-grasp kinematics.
(A) Average maximum reach extent across sessions for ‘during reach’ inhibition. Linear mixed model: effect of laser: t(63) = −1.72, p=0.09; interaction between laser and session: t(585) = 0.03, p=0.98. (B) Same as (A) for ‘between reach’ inhibition. Linear mixed model: effect of laser: t(63) = −0.23, p=0.82; interaction between laser and session: t(585) = 0.99, p=0.32. Figure 7—figure supplement 1 shows the relationship between reach extent and fiber tip location for these groups. (C) Moving average of maximum reach extent within the last ‘retraining’ sessions, first 6 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. (D) Same as (A) for aperture: effect of laser: t(48) = 0.53, p=0.60; interaction between laser and session: t(585) = 1.76, p=0.08. (E) Moving average of grasp aperture at reach end within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (F) Same as (A) and (D) for paw orientation: effect of laser: t(75) = −0.20, p=0.84; interaction between laser and session: t(585) = −0.28, p=0.78. (G) Moving average of paw angle at reach end within the last ‘retraining' session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (H) Same as (A), (D), and (F) for maximum reach velocity: effect of laser: t(49) = −0.52, p=0.60; interaction between laser and session: t(585) = −1.68, p=0.09. (I) Moving average of maximum reach velocity within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Shaded colored areas in C, E, G, I and error bars in A, B, D, H represent s.e.m. Similar data for Arch Between rats are shown in Figure 7—figure supplement 2. Individual rat data are shown in Figure 7—figure supplements 3–6. Figure 7—figure supplement 7 compares kinematic measures (final zdigit2, aperture, paw orientation, and maximum reach velocity) between successful and unsuccessful reaches for Arch during and Arch between rats. Figure 7—figure supplement 8 shows success rate and kinematic measures as a function of final zdigit2 for Arch during and Arch between rats. Black bars in (E) and (G) represent trials with a statistically significant difference between groups (Wilcoxon rank sum test, p<0.01).
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Figure 7—source data 1
A .mat file containing maximum reach extent of digit2 (mean_dig2_endPt), aperture at reach end (mean_end_aperture), paw orientation at reach end (mean_end_orientations), and mean paw velocity (mean_pd_v) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-data1-v2.mat
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Figure 7—source data 2
A .mat file containing digit2 endpoint (digEnd), aperture at reach end (aperture), orientation at reach end (orientation), and velocity (velocity) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-data2-v2.mat
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Figure 7—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between Arch During and EYFP group averages in Figures 6D, F, H and J.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-data3-v2.xlsx
Figure 7—figure supplement 1
Maximum reach extent on laser day 10 as a function of anterior-posterior, medial-lateral, and dorsal-ventral fiber tip coordinates referenced to bregma (A–P and M–L) or brain surface (D–V).
The same symbol represents the same rat across panels within each group. r and p values are for linear regressions fit to each plot. (A) ‘Arch during’ group. (B) ‘Arch between’ group.
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Figure 7—figure supplement 1—source data 1
A .mat file containing digit2 endpoints (mean_dig2_endPt) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp1-data1-v2.mat
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Figure 7—figure supplement 1—source data 2
A .xlsx file containing the estimated fiber tip locations for each rat in all groups.
Virus 1 = ‘ChR2 During’; Virus 2 = ‘ChR2 Between’; Virus 3 = ‘Arch During’; Virus 4 = ‘Arch Between’; Virus 5 = ‘EYFP’.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp1-data2-v2.xlsx
Figure 7—figure supplement 2
Reach-to-grasp kinematics do not change with dopamine neuron inhibition between reaches.
(A) Moving average of maximum reach extent for ‘between reach’ inhibition within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 5 ‘occlusion’ sessions. Data for ‘during reach’ inhibition from Figure 7C are shown here for comparison. (B) Average aperture at reach end for ‘between reach’ inhibition. Linear mixed model: effect of laser: t(48) = 0.05, p=0.96; interaction between laser and session: t(585) = 0.26, p=0.80. (C) Moving average of aperture at reach end for ‘between reach’ inhibition within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (D) Same as (B) for paw orientation: effect of laser: t(75) = −0.11, p=0.91; interaction between laser and session: t(585) = 0.50, p=0.62. (E) Moving average of paw angle at reach end for ‘between reach’ inhibition within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. (F) Same as (B) and (D) for maximum reach velocity: effect of laser: t(49) = −0.19, p=0.85; interaction between laser and session: t(585) = 0.49, p=0.62. (G) Moving average of maximum reach velocity at reach end for ‘between reach’ inhibition within the last ‘retraining’ session, first 6 ‘laser on’ sessions, and first 4 ‘occlusion’ sessions. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc. Shaded colored areas in A, C, E, G and error bars in B, D, F represent s.e.m.
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Figure 7—figure supplement 2—source data 1
A .mat file containing aperture at reach end (mean_end_aperture), paw orientation at reach end (mean_end_orientations), and mean paw velocity (mean_pd_v) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp2-data1-v2.mat
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Figure 7—figure supplement 2—source data 2
A .mat file containing digit2 endpoint (digEnd), aperture at reach end (aperture), orientation at reach end (orientation), and velocity (velocity) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp2-data2-v2.mat
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Figure 7—figure supplement 2—source data 3
Statistics.
A .xlsx file containing the statistical output of Wilcoxon ranksum tests for comparisons between Arch During and Arch Between group averages in Figure 7—figure supplement 2 panels A, C, E, and G.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp2-data3-v2.xlsx
Figure 7—figure supplement 3
Individual rat data for moving average of maximum reach extent within individual sessions (‘Arch During’ and ‘Arch Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 7—figure supplement 3—source data 1
A .mat file containing digit2 endpoint (digEnd) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp3-data1-v2.mat
Figure 7—figure supplement 4
Individual rat data for moving average of grasp aperture at reach end within individual sessions (‘Arch During’ and ‘Arch Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 7—figure supplement 4—source data 1
A .mat file containing aperture at reach end averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp4-data1-v2.mat
Figure 7—figure supplement 5
Individual rat data for moving average of paw angle at reach end within individual sessions (‘Arch During’ and ‘Arch Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 7—figure supplement 5—source data 1
A .mat file containing orientation at reach end averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp5-data1-v2.mat
Figure 7—figure supplement 6
Individual rat data for moving average of maximum reach velocity within individual sessions (‘Arch During’ and ‘Arch Between’).
Each colored line represents the same rat across panels. ‘R10’, ‘L1’, ‘O1’, etc. indicate the 10th retraining session, first ‘laser on’ session, first ‘occlusion’ session, etc.
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Figure 7—figure supplement 6—source data 1
A .mat file containing reach velocity averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp6-data1-v2.mat
Figure 7—figure supplement 7
Kinematic measures separated by reach success or failure for Arch during (left column) and Arch between (right column) groups.
(A) Average maximum reach extent. There was no significant difference in maximum reach extent by outcome during ‘Laser On’ sessions for Arch during (interaction between laser and outcome: t(1188) = 1.45, p=0.15; interaction between session, laser, and outcome: t(1188) = −1.18, p=0.24) or Arch between groups (interaction between laser and outcome: t(1188) = 1.19, p=0.23; interaction between session, laser, and outcome: t(1188) = −1.16, p=0.25). (B) Same as (A) for aperture at the end of the reach. There was no significant difference in aperture by outcome during ‘Laser On’ sessions for Arch during (interaction between laser and outcome: t(1163) = −1.39, p=0.17; interaction between session, laser, and outcome: t(1164) = 1.25, p=0.21) or Arch between groups (interaction between laser and outcome: t(1163) = −1.30, p=0.19; interaction between session, laser, and outcome: t(1163) = 0.92, p=0.36). (C) Same as (A) for reach orientation at the end of the reach. There was no significant difference in orientation by outcome during ‘Laser On’ sessions for Arch during (interaction between laser and outcome: t(1184) = 0.23, p=0.82; interaction between session, laser, and outcome: t(1186) = −0.16, p=0.88) or Arch between groups (interaction between laser and outcome: t(1184) = 0.92, p=0.36; interaction between session, laser, and outcome: t(1184) = −0.76, p=0.45). (D) Same as (A) for maximum reach velocity. There was no significant difference in velocity by outcome during ‘Laser On’ sessions for Arch during (interaction between laser and outcome: t(1187) = 0.21, p=0.84; interaction between session, laser, and outcome: t(1188) = −0.72, p=0.47) or Arch between groups (interaction between laser and outcome: t(1187) = 0.18, p=0.86; interaction between session, laser, and outcome: t(1187) = −0.17, p=0.87).
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Figure 7—figure supplement 7—source data 1
A .mat file containing digit2 endpoint (mean_dig2_endPt_z), aperture at reach end (mean_end_aperture), orientation at reach end (mean_end_orientation), and reach velocity (mean_pd_v) separated by trial outcome.
Each column is a different outcome type, which are specified in the field ‘outcomeNames’ (e.g. column two is first reach success).
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp7-data1-v2.mat
Figure 7—figure supplement 8
Differences between reaches matched for reach extent in the Arch during (left column) and Arch between (right column) groups.
(A) Average number of trials per session with different initial reach extents in each group. (B) Average success rate as a function of reach extent across groups. (C) Same as (B) for aperture at reach end. (D) Same as (B) and (C) for paw orientation at reach end. # indicates p<0.05 for comparisons between laser on and occluded (paired t-tests).
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Figure 7—figure supplement 8—source data 1
A .mat file containing digit2 endpoint (digEnd), aperture at reach end (aperture), orientation at reach end (orient), and trial outcomes (outcome) for all trials across all sessions for each rat.
The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp8-data1-v2.mat
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Figure 7—figure supplement 8—source data 2
Statistics.
A .xlsx file containing statistical output for paired t-test comparisons between ‘laser on’ and ‘retraining’ sessions and between ‘laser on’ and ‘occluded’ sessions for Arch During and ChR2 Between groups. ‘Z Block’ is the 10 groups of trials stratified by their maximum zdigit2 extent.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig7-figsupp8-data2-v2.xlsx
Figure 8
Dopamine neuron stimulation alters the coordination between digit movements and paw advancement.
(A) Sample frames from single reaches at the end of ‘retraining’ and ‘laser on’ sessions from the same rat. Outer columns show the mirror views corresponding to the direct camera views in the inside columns. After 10 days of ‘during reach’ stimulation, the rat pronates its paw and spreads its digits further from the pellet as the paw advances. (B) Aperture as a function of the z-coordinate of the second digit tip. Solid black and blue lines correspond to the reaches shown in (A). Thin black and blue lines are the traces for other reaches in the same sessions. Circles indicate apertures at the corresponding zdigit2 values in (A). (C) Same as (B) but for paw orientation.
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Figure 8—source data 1
A zip file containing .mat files to produce Figure 8.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig8-data1-v2.zip
Figure 9 with 5 supplements
Dopamine neuron manipulations disrupt coordination of reach-to-grasp movements.
(A) Mean aperture as a function of paw advancement (zdigit2, pellet at zdigit2 = 0) across ‘laser on’ and ‘occlusion’ sessions for exemplar rats. L1-2, O1-2, … indicate laser on sessions 1–2, occlusion sessions 1–2, etc. (B) Mean aperture as a function of paw advancement across ‘laser on’ and ‘occlusion’ sessions averaged across rats. 4 of 6 ‘ChR2 During’ rats are included because two rats’ reaches were too short in several sessions to produce a meaningful average (the average for all 6 ChR2 During rats, ChR2 Between rats, and Arch Between rats are shown in Figure 9—figure supplement 1). All rats were included for other groups. Dashed lines indicate the zdigit2 coordinate where data are sampled in (C). A more proximal zdigit2 was chosen for ‘ChR2 During’ because the majority of ‘laser on’ reaches for this group did not extend past zdigit2 = +1 mm. (C) Average grasp aperture at the zdigit2 coordinates indicated by the dashed lines in (B) across sessions. ‘During reach’ stimulation gradually increased aperture at 7 mm from the pellet (linear mixed model including all 6 ‘during reach’ rats: effect of laser: t(607) = 2.39, p=0.02; interaction between laser and session: t(607) = 2.40, p=0.02). ‘During reach’ inhibition decreased aperture at 1 mm past the pellet (linear mixed model: effect of laser: t(607) = −2.04, p=0.04; interaction between laser and session: t(607) = 0.67, p=0.51). SNc illumination in EYFP-injected rats had no effect on aperture at 1 mm past the pellet (linear mixed model: effect of laser: t(607) = −0.57, p=0.57; interaction between laser and session: t(607) = −0.61, p=0.54). Gray points indicate data from individual rats. (D) Mean paw orientation as a function of paw advancement towards the pellet across ‘laser on’ and ‘occlusion’ sessions for exemplar rats. All rats are shown in Figure 9—figure supplement 4. (E) Mean paw orientation as a function of paw advancement across ‘laser on’ and ‘occlusion’ sessions averaged across rats. Dashed lines indicate zdigit2 coordinates where data are sampled in (F) for each group. Four of 6 ‘ChR2 During’ rats are included because two rats’ reaches were too short in several sessions to produce a meaningful average (the average for all 6 ChR2 During rats, ChR2 Between rats, and Arch Between rats are shown in Figure 9—figure supplement 1). (F) Average paw orientation at zdigit2 coordinates indicated by dashed lines in (E) across all sessions. ‘During reach’ stimulation caused a gradual increase in pronation (i.e. a smaller angle) at 7 mm from the pellet (linear mixed model including all 6 ‘during reach’ rats: effect of laser: t(607) = −2.34, p=0.02; interaction between laser and session: t(607) = −2.33, p=0.02). ‘During reach’ inhibition had no effect on paw orientation at 1 mm past the pellet (linear mixed model: effect of laser: t(607) = 0.88, p=0.38; interaction between laser and session: t(607) = −0.55, p=0.58). SNc illumination in EYFP-injected rats had no effect on paw orientation at 1 mm past the pellet (linear mixed model: effect of laser: t(607) = −0.51, p=0.61; interaction between laser and session: t(607) = 0.31, p=0.76). Gray points indicate data from individual rats. * indicates p<0.05 for either the laser or laser-session interaction terms in panels C and F. Aperture and orientation as a function of zdigit2 for successful and failed reaches are shown in Figure 9—figure supplements 2,3, respectively. Aperture and orientation as a function of zdigit2 are shown for each rat individually in Figure 9—figure supplements 4,5, respectively.
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Figure 9—source data 1
A .mat file containing aperture (mean_aperture_traj) and paw orientation (mean_orientation_traj) data along reach trajectories (see Materials and methods for details of calculations) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-data1-v2.mat
Figure 9—figure supplement 1
Dopamine manipulations between reaches do not affect reach-to-grasp coordination.
(A) Mean aperture as a function of paw advancement in all ‘ChR2 During’ rats (n = 6). L1-2, O1-2, … indicate laser on sessions 1–2, occlusion sessions 1–2, etc. (B) Mean aperture as a function of paw advancement for ‘between reach’ stimulation. (C) Mean aperture as a function of paw advancement for ‘between reach’ inhibition. (D) Average aperture at zdigit2 coordinates indicated by dashed lines in (B) and (C) across all sessions. ‘Between reach’ dopamine neuron stimulation did not affect aperture 7 mm from the pellet (linear mixed model: effect of laser: t(607) = 0.37, p=0.71; interaction between laser and session: t(607) = 0.07, p=0.94) or 1 mm past the pellet (linear mixed model: effect of laser: t(607) = 0.53, p=0.60; interaction between laser and session: t(607) = −0.56, p=0.58). Dopamine neuron inhibition between reaches did not affect aperture 1 mm past the pellet (linear mixed model: effect of laser: t(607) = −0.90, p=0.37; interaction between laser and session: t(607) = 1.82, p=0.07). (E) Mean paw orientation as a function of paw advancement in all ‘ChR2 During’ rats (n = 6). (F) Mean paw orientation as a function of paw advancement for ‘between reach’ stimulation. (G) Mean paw orientation as a function of paw advancement for ‘between reach’ inhibition. (H) Average paw orientation at zdigit2-coordinates indicated by dashed lines in (F) and (G) across all sessions. ‘Between reach’ dopamine neuron stimulation did not affect paw orientation at 7 mm from the pellet (linear mixed model: effect of laser: t(607) = 0.27, p=0.79; interaction between laser and session: t(607) = 0.22, p=0.82) or 1 mm past the pellet (linear mixed model: effect of laser: t(607) = −0.41, p=0.68; interaction between laser and session: t(607) = 1.17, p=0.24). Dopamine neuron inhibition between reaches did not affect paw orientation at 1 mm past the pellet (linear mixed model: effect of laser: t(607) = 0.61, p=0.54; interaction between laser and session: t(607) = −0.36, p=0.72).
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Figure 9—figure supplement 1—source data 1
A .mat file containing aperture (mean_aperture_traj) and paw orientation (mean_orientation_traj) data along reach trajectories (see Materials and methods for details of calculations) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp1-data1-v2.mat
Figure 9—figure supplement 2
Mean aperture as a function of paw advancement separated by reach success or failure.
(A) Mean aperture as a function of paw advancement (zdigit2, pellet at zdigit2 = 0) across only ‘laser on’ sessions separated by whether the initial reach was successful (green) or not (red). Dashed lines indicate the zdigit2 coordinate where data are sampled in (B) for each group. A more proximal zdigit2 was chosen for ChR2 groups because the majority of ‘laser on’ reaches for the ‘ChR2 During’ group did not extend past zdigit2 = +1 mm. (B) Average grasp aperture at the zdigit2 coordinates indicated by the dashed lines in (A) across sessions. Aperture did not differ between successful and failed reaches for any groups in the linear mixed model (‘ChR2 During’: interaction between laser and outcome: t(1210) = 0.27, p=0.79; interaction between session, laser, and outcome: t(1210) = −1.50, p=0.13. ‘ChR2 Between’: interaction between laser and outcome: t(1210) = −0.41, p=0.68; interaction between session, laser, and outcome: t(1210) = 0.30, p=0.77. ‘Arch During’: interaction between laser and outcome: t(1210) = 0.70, p=0.49; interaction between session, laser, and outcome: t(1210) = −0.59, p=0.55. ‘Arch Between’: interaction between laser and outcome: t(1210) = 0.54, p=0.59; interaction between session, laser, and outcome: t(1210) = −0.72, p=0.47. ‘EYFP’: interaction between laser and outcome: t(1210) = 0.06, p=0.95; interaction between session, laser, and outcome: t(1210) = 0.35, p=0.73). However, contrast testing revealed differences between successful and failed reaches for ChR2 During rats in laser on sessions 3–10 (t(1210) = −2.42, p=0.02; t(1210) = −3.31, p=9.63×10−4; t(1210) = −4.17, p=3.30×10−5; t(1210) = −4.63, p=4.06×10−6; t(1210) = −4.59, p=4.86×10−6; t(1210) = −4.29, p=1.92×10−5; t(1210) = −3.95, p=8.44×10−5; t(1210) = −3.64, p=2.89×10−4) and for Arch During rats on session 6 (t(1210) = −2.00, p=0.045). * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001 for contrast tests comparing successful to failed reaches for each session.
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Figure 9—figure supplement 2—source data 1
A .mat file containing aperture (mean_aperture_traj) data along reach trajectories (see Materials and methods for details of calculations) separated according to trial outcome.
Outcome types are specified in the field ‘outcomeNames’.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp2-data1-v2.mat
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Figure 9—figure supplement 2—source data 2
Statistics.
A .xlsx file containing statistical output of post hoc contrast tests comparing mean aperture in successful and failed reaches for each group in panel B.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp2-data2-v2.xlsx
Figure 9—figure supplement 3
Mean paw orientation as a function of paw advancement separated by reach success or failure.
(A) Mean orientation as a function of paw advancement (zdigit2, pellet at zdigit2 = 0) across ‘laser on’ sessions separated by whether the initial reach was successful (green) or not (red). Dashed lines indicate the zdigit2 coordinate where data are sampled in (B) for each group. A more proximal zdigit2 was chosen for ChR2 groups because the majority of ‘laser on’ reaches for the ‘ChR2 During’ group did not extend past zdigit2 = +1 mm. (B) Average paw orientation at the zdigit2 coordinates indicated by the dashed lines in (A) across sessions. Orientation did not differ between successful and failed reaches for any groups. Linear mixed model: ‘ChR2 During’: interaction between laser and outcome: t(1210) = −0.04, p=0.97; interaction between session, laser, and outcome: t(1210) = 0.04, p=0.97. ‘ChR2 Between’: interaction between laser and outcome: t(1210) = −0.20, p=0.84; interaction between session, laser, and outcome: t(1210) = 0.71, p=0.48. ‘Arch During’: interaction between laser and outcome: t(1210) = −0.50, p=0.62; interaction between session, laser, and outcome: t(1210) = 0.77, p=0.44. ‘Arch Between’: interaction between laser and outcome: t(1210) = −0.01, p=0.99; interaction between session, laser, and outcome: t(1210) = 0.29, p=0.77. ‘EYFP’: interaction between laser and outcome: t(1210) = 0.22, p=0.83; interaction between session, laser, and outcome: t(1210) = −0.40, p=0.69.
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Figure 9—figure supplement 3—source data 1
A .mat file containing paw orientation (mean_orientation_traj) data along reach trajectories (see Materials and methods for details of calculations) separated according to trial outcome.
Outcome types are specified in the field ‘outcomeNames’.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp3-data1-v2.mat
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Figure 9—figure supplement 3—source data 2
Statistics.
A .xlsx file containing statistical output of post hoc contrast tests comparing mean orientation in successful and failed reaches for each group in panel B.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp3-data2-v2.xlsx
Figure 9—figure supplement 4
Mean aperture as a function of paw advancement for each rat.
From top to bottom: ChR2 during reach stimulation, ChR2 between reach stimulation, Arch during reach inhibition, Arch between reach inhibition and EYFP during reach stimulation. * indicates rats that were excluded from averaged data in Figure 9B (see Materials and methods). In the legend, L1-2, O1-2, … indicate laser on sessions 1–2, occlusion sessions 1–2, etc.
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Figure 9—figure supplement 4—source data 1
A .mat file containing aperture (mean_aperture_traj) data along reach trajectories (see Materials and methods for details of calculations) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp4-data1-v2.mat
Figure 9—figure supplement 5
Mean paw orientation as a function of paw advancement for each rat.
From top to bottom: ChR2 during reach stimulation, ChR2 between reach stimulation, Arch during reach inhibition, Arch between reach inhibition, and EYFP during reach stimulation. * indicates rats that were excluded from averaged data in Figure 9E (see Materials and methods). In the legend, L1-2, O1-2, … indicate laser on sessions 1–2, occlusion sessions 1–2, etc.
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Figure 9—figure supplement 5—source data 1
A .mat file containing paw orientation (mean_orientation_traj) data along reach trajectories (see Materials and methods for details of calculations) for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig9-figsupp5-data1-v2.mat
Figure 10 with 2 supplements
Dopamine neuron stimulation induces distinct reach-to-grasp kinematics that depend on current dopamine stimulation.
(A) Experimental timeline for ‘ChR2 between’ rats. After 10 sessions of testing with the laser occluded, ‘ChR2 between’ rats underwent two to eight sessions (average: 3.17 ± 0.98 sessions) with ‘during reach’ stimulation. 'AIMs 1' and 'AIMs 2' indicate the timing of abnormal involuntary movement testing. Once reaching movements were impaired (Panels B-C and Figure 10—figure supplements 1,2), rats underwent testing with laser off and on for blocks of five trials (Panels D-J). (B) Average maximum reach extent on the last day of testing with the laser occluded between reaches (O10) and the first 2 days of testing with the laser on during reaches (L1 and L2). Maximum reach extent decreased significantly between O10 and L1 (linear mixed model: t(14) = −2.58, p=0.02) and O10 and L2 (linear mixed model: t(14) = −4.33, p=6.92×10−4). (C) Moving average of maximum reach extent for last day of testing with the laser occluded between reaches and the first 2 days of testing with the laser on during reaches. Additional kinematic measures (aperture, orientation, reach velocity) are shown in Figure 10—figure supplement 1. Individual rat data are shown in Figure 10—figure supplement 2. (D) Schematic of alternating stimulation test sessions. (E) Example session from one rat with maximum reach extent plotted for every trial. Some blocks have fewer than five trials if the rat did not reach for the pellet after breaking the IR beam. (F) Average first attempt success rate during ‘laser off’ and ‘laser on’ blocks. Data are repeated to show ‘off to on’ and ‘on to off’ transitions in panels F-J. Gray lines show individual rat data. Linear mixed model: effect of laser: t(78) = −0.50, p=0.62; interaction between laser and trial within block: t(78) = −2.35, p=0.02. (G) Average maximum reach extent during ‘laser off’ and ‘laser on’ blocks. Linear mixed model: effect of laser: t(78) = 2.70, p=8.47×10−3; interaction between laser and trial within block: t(78) = 1.32, p=0.19. (H) Average aperture at reach end across ‘laser off’ and ‘laser on’ blocks. Linear mixed model: effect of laser: t(78) = −2.83, p=5.92×10−3; interaction between laser and trial within block: t(78) = −0.79, p=0.43. (I) Average paw orientation at reach end across ‘laser off’ and ‘laser on’ blocks. Linear mixed model: effect of laser: t(78) = 2.57, p=0.01; interaction between laser and trial within block: t(78) = −0.34, p=0.73. (J) Average maximum reach velocity across ‘laser off’ and ‘laser on’ blocks. Linear mixed model: effect of laser: t(78) = −1.24, p=0.22; interaction between laser and trial within block: t(78) = 0.01, p=0.99. * indicates p<0.05 for effect of laser in panel F. ** indicates p<0.01 for effect of laser in panel D.
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Figure 10—source data 1
A .mat file containing zdigit2 endpoint (mean_dig2_endPt) data for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-data1-v2.mat
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Figure 10—source data 2
A .mat file containing zdigt2 endpoint (mean_dig2_endPt) data for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
Data is average per session for each rat.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-data2-v2.mat
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Figure 10—source data 3
A .mat file containing digit2 endpoint (digEnd) averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-data3-v2.mat
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Figure 10—source data 4
A .mat file containing digit2 endpoint (digEnd) averages across a moving block of 10 trials for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-data4-v2.mat
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Figure 10—source data 5
A .mat file containing ‘5off/5on’ data.
Data includes digit2 endpoint (dig_endPoints), aperture, orientation, and velocity (max_pd_v).
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-data5-v2.mat
Figure 10—figure supplement 1
Additional kinematic measures for ‘during reach’ stimulation testing in ‘ChR2 between’ rats.
(A) Average aperture at reach end on the last day of testing with the laser occluded between reaches (O10) and the first 2 days of testing with the laser on during reaches. Aperture decreased significantly between O10 and L1 (linear mixed model: t(14) = −2.84, p=0.01) and O10 and L2 (linear mixed model: t(14) = −5.72, p=5.30×10−5). (B) Moving average of aperture for last day of testing with the laser occluded between reaches and the first 2 days of testing with the laser on during reaches. (C) Same as (A) for paw orientation. Paw orientation did not differ significantly between O10 and L1 (linear mixed model: t(14) = 1.89, p=0.08) and O10 and L2 (linear mixed model: t(14) = 2.06, p=0.06). (D) Same as (B) for paw orientation. (E) Same as (A) and (C) for maximum reach velocity. Velocity decreased significantly between O10 and L1 (linear mixed model: t(14) = −2.69, p=0.02) and O10 and L2 (linear mixed model: t(14) = −3.71, p=2.35×10−3). (F) Same as (B) and (D) for maximum reach velocity.
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Figure 10—figure supplement 1—source data 1
A .mat file containing aperture (mean_end_aperture), paw orientation (mean_end_orientations), and velocity (mean_pd_v) data for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
Data is average per session for each rat. The field ‘experimentInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp1-data1-v2.mat
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Figure 10—figure supplement 1—source data 2
A .mat file containing aperture (mean_end_aperture), paw orientation (mean_end_orientations), and velocity (mean_pd_v) data for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
Data is average per session for each rat.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp1-data2-v2.mat
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Figure 10—figure supplement 1—source data 3
A .mat file containing aperture, paw orientation, and velocity averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp1-data3-v2.mat
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Figure 10—figure supplement 1—source data 4
A .mat file containing aperture, paw orientation, and velocity averages across a moving block of 10 trials for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp1-data4-v2.mat
Figure 10—figure supplement 2
Individual rat data for moving average of maximum reach extent, aperture at reach end, paw orientation at reach end, and maximum reach velocity within individual sessions.
Each colored line represents the same rat across panels. ‘O10’, ‘L1’, and ‘L2’, indicate the 10th occlusion session with laser on between reaches and the first and second ‘laser on’ sessions with stimulation during reaches.
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Figure 10—figure supplement 2—source data 1
A .mat file containing digit2 endpoint, aperture, paw orientation, and velocity averages across a moving block of 10 trials for 22 testing sessions (‘retraining’, ‘laser on’, and ‘occluded’).
The field ‘exptInfo’ provides information on groups.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp2-data1-v2.mat
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Figure 10—figure supplement 2—source data 2
A .mat file containing digit2 endpoint, aperture, paw orientation, and velocity averages across a moving block of 10 trials for ‘during reach’ sessions in originally ‘ChR2 Between’ rats.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig10-figsupp2-data2-v2.mat
Figure 11 with 1 supplement
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.
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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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig11-data1-v2.mat
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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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig11-data2-v2.mat
Figure 11—figure supplement 1
Dyskinesias in the second AIMs test do not consistently predict changes in reach success rate.
(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.
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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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig11-figsupp1-data1-v2.mat
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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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig11-figsupp1-data2-v2.mat
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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.
- https://cdn.elifesciences.org/articles/61591/elife-61591-fig11-figsupp1-data3-v2.mat
Videos
Video 1
Sample reach during the last ‘retraining’ session of a ‘ChR2-During’ rat showing the direct camera view, the mirror view of the paw dorsum, and 3D skeleton reconstruction.
Two trailing points are shown for each body part/object. Video is slowed 10x.
Video 2
Sample reach during the seventh ‘laser on’ session for the same rat as in Video 1 showing the direct camera view, the mirror view of the paw dorsum, and 3D skeleton reconstruction.
Two trailing points are shown for each body part/object. Video is slowed 10x.
Video 3
Sample reach during the last ‘retraining’ session of an ‘Arch-During’ rat showing the direct camera view, the mirror view of the paw dorsum, and 3D skeleton reconstruction.
Two trailing points are shown for each body part/object. Video is slowed 10x.
Video 4
Sample reach during the tenth ‘laser on’ session for the same rat as in Video 3 showing the direct camera view, the mirror view of the paw dorsum, and 3D skeleton reconstruction.
While the reaches in Video 3 and 4 are superficially similar, the rat reaches further past the pellet after repeated dopamine neuron inhibition. Two trailing points are shown for each body part/object. Video is slowed 10x.
Video 5
Sample reaches from a rat that received ‘during reach’ stimulation in alternating trial blocks demonstrating that kinematic changes induced by dopamine neuron stimulation are enduring.
Reach 1 – at baseline, the rat extends its paw past the pellet to grasp it. Reach 2 – after several reaches with stimulation, the second digit extends just to the pellet, which is knocked off the pedestal. Reach 3 – after more reaches with stimulation, the reach comes far short of the pellet. Reach 4 – with stimulation off, reach kinematics return to baseline. Reach 5 – on the next reach, stimulation is reinstated and kinematics are markedly abnormal.
Video 6
Context-dependent AIMs.
ChR2-injected rat showing AIMs (axial and limb dyskinesias) with dopamine neuron stimulation during the second day of AIMs testing. The second segment shows a reach in which the same rat does not show AIMs when receiving the same stimulation parameters (estimated 20 mW at the fiber tip, 20 Hz) during a reach.
Video 7
AIMs during reaching in a ‘ChR2 during’ rat during ‘laser on’ session 10 (same rat as in Video 6).
The first segment shows an example of a non-dyskinetic reach. While the reach is hypometric, the motion is smooth. The last segment shows a reach during the same session in which dyskinesias interfered with the reach (limb amplitude score = 1). The red dot indicates moments when the rat is showing AIMs (paw is oscillating from left to right instead of moving towards or away from the pellet). Videos are shown at normal and 20% speed.
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (TH-Cre Long-Evans rats, male and female) | LE-Tg(TH-Cre)3.1Deis | Rat Resource and Research Center | RRRC#: 00659; RRID:RGD_10401201 | |
| Antibody | anti-GFP (Mouse monoclonal) | Millipore Sigma | Cat. #: MAB3580; RRID:AB_94936 | (1:1500) |
| Antibody | anti-TH (Rabbit polyclonal) | Millipore Sigma | Cat. #: AB152; RRID:AB_390204 | (1:2000) |
| Antibody | Alexa Fluor 488 donkey anti-mouse IgG (Donkey polyclonal) | Thermo Fisher | Cat. #: A-21202; RRID:AB_141607 | (1:500) |
| Antibody | Alexa Fluor 555 donkey anti-rabbit IgG (Donkey polyclonal) | Thermo Fisher | Cat. #: A-31572; RRID:AB_162543 | (1:500) |
| Recombinant DNA reagent | AAV5-EF1α-DIO-hChR2 (H134R)-EFYP | UNC Vector Core | ||
| Recombinant DNA reagent | AAV5-EF1α-DIO-eArch3.0-EYFP | UNC Vector Core | ||
| Recombinant DNA reagent | AAV-EF1α-DIO-EYFP | UNC Vector Core | ||
| Software, algorithm | Matlab | Mathworks | RRID:SCR_001622 | |
| Software, algorithm | RStudio | RStudio PBC | RRID:SCR_000432 | |
| Other | ProLong Diamond | Invitrogen | Cat. #: P36961 |
Additional files
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Precisely timed dopamine signals establish distinct kinematic representations of skilled movements
eLife 9:e61591.
https://doi.org/10.7554/eLife.61591
