Fig. 3: Optogenetically evoked dopamine release in DLS reinforces syllable use and increases sequence variability.
From: Spontaneous behaviour is structured by reinforcement without explicit reward
a, The closed-loop MoSeq pipeline. b, Schematic and representative brain section of fibre cannulae over DLS dopamine axons. c, Top, normalized optogenetically evoked dLight peak magnitude distribution (n = 842 peaks). Bottom, mean waveforms from spontaneous and Opto-DA transients (Methods). Shading represents the 95% bootstrapped confidence interval. Max, maximum. d, Experimental schedule describing baseline (rec.) and stimulation (stim.) sessions for ‘target’ syllables (Methods). e, log2 fold change in target counts compared with baseline, per mouse, averaged across targets (P = 0.002, U = 197, f = 0.82, one-sided Mann–Whitney U test) (see Methods for definition of ‘learner’). f, Cumulative increase in target counts relative to baseline in Opto-DA and control mice (P = 0.007, U = 184, f = 0.77, one-sided Mann–Whitney U test). g, Cumulative counts over concatenated stimulation sessions per target. Shading indicates bootstrap s.e.m. h, The relationship between target syllable usage changes from baseline during stimulation experiments versus post-stimulation experiments per mouse (Pearson r = 0.89, P = 0.005 for learners and P = 0.082 for controls, one-sided shuffle test). NS, not significant. i, Average transition entropy following stimulation. Shading indicates bootstrap s.e.m. The light grey band indicates the 95% confidence interval of the pre-stimulation average. Data are binned using five-syllable-wide non-overlapping bins. The bar indicates significance (P < 0.05 for Opto-DA mice, P > 0.05 for controls, two-sided Mann–Whitney U test comparing stimulation with catch trials). Syll, syllable. j, Sequence context changes from baseline to post-stimulation for an example mouse–target pair. Sequences proceed from left (incoming syllables) to right (outgoing syllables). Nodes are sorted by decreasing frequency at baseline. k, Average change in inbound and outbound transitions for target syllables on stimulation day sorted by the baseline rank of the transition. Traces are smoothed with a five-point rolling average. Shading indicates bootstrap s.e.m. l, Average kinematic parameters aligned to stimulation in Opto-DA mice and controls. Shading as in i. No comparisons between stimulation and catch trials in any of the mice were significant (P > 0.05, one-sided Mann–Whitney U test). m, As in l, but following 3-s-long stimulation. The solid bar indicates significance (P < 0.05, one-sided Mann–Whitney U test).
