Fig. 3: Optogenetic DA manipulations do not affect the vigor of ongoing movements.
From: Subsecond dopamine fluctuations do not specify the vigor of ongoing actions
a, Experimental setup for optogenetic inhibition of mDANs. b, Left: confocal image of ventral midbrain (coronal plane) showing stGtACR2 (red) in mDANs immunostained for TH (green). Right: mean stGtACR2 penetrance in 11,243 mDANs from N = 6 mice. c, Left: example rDA1m signal recorded in DLS during blue light delivery (470 nm, 10 mW for 2 s) in the midbrain of mice expressing stGtACR2 (opsin+) or not (opsin−). Right: summary plot of mean change in rDA1m fluorescence. d, Top: representative lever trajectories from one example session (thick line, session-wide mean) for presses occurring on trials with optogenetic light off (left) or not (right). Bottom: peak velocity and amplitude of all presses performed during that example session, separated between control trials (gray; n = 127 presses) and mDAN inhibition trials (blue; n = 55 presses; velocity: P = 0.74; amplitude: P = 0.58, two-sample t-tests). Black bar, session median. e, Left: scatter plot of median peak press velocity for trials with mDAN inhibition (30%) versus trials without (70%) within the same session. Right: same data expressed as a change in peak press velocity for each session. Blue, mDAN inhibition sessions using blue light on 30% of trials (n = 18 sessions from 6 mice, 3 sessions each); gray, sham inhibition sessions using no light (n = 18 sessions from the same 6 mice, 3 sessions each; P = 0.48, mixed-effect model). f, Same as in e for press amplitude (P = 0.70, mixed-effect model). g, Experimental setup for optogenetic activation of mDANs. h, Example rDA1m signal during reward (top) and optogenetic mDAN activation (bottom; 470 nm, 4 mW, 10-ms pulses at 30 Hz for 1 s). i, Mean (± s.e.m.) DA transient amplitude (N = 4 mice). Individual mice shown in gray. j, Same as in d for one example session in which mDANs are optogenetically activated on ~30% of trials (control: n = 165 presses; optogenetic stimulation: n = 70 presses; peak velocity: P = 0.89; amplitude: P = 0.56, two-sample t-tests). k, Same as in e for optogenetic activation of mDANs. Blue, stimulation sessions using blue light (n = 18 sessions from 6 mice, 3 sessions each); gray, sham sessions using red light (n = 18 sessions from the same 6 mice, 3 sessions each; P = 0.83, mixed-effect model). l, Same as in k for press amplitude (P = 0.53, mixed-effect model). m, Same as in e before versus after mid-session change in reward threshold. Magenta, sessions in which threshold is increased (Δ threshold > 0); gray, control sessions in which threshold is kept constant (Δ threshold = 0; P = 0.0023, mixed-effect model). n, Same as in m for press amplitude (P = 6.3 × 10−7, mixed-effect model). In b, e, f and k–n, summary data (black) are population mean ± s.e.m. Example traces in c and h are the mean ± s.e.m. of a minimum of 10 repeats. Opto., optogenetic.
