Fig. 4: Optogenetic syllable reinforcement varies predictably across mice and syllables.
From: Spontaneous behaviour is structured by reinforcement without explicit reward
a, Schematic depicting the relationship between observed endogenous dopamine-syllable usage correlations and per-mouse dopamine sensitivity. Dopamine (DA) sensitivity refers to the ability of endogenous, syllable-associated dopamine peaks to influence changes in syllable counts (Endo-DA count influence) or sequencing (Endo-DA entropy influence) within an experiment (see Methods for how indices were computed). b, Top, the distribution of per mouse Endo-DA count influence (left) and Endo-DA entropy influence (right) averaged across all syllables. Bottom, scatter plot (including linear regression model fit) of per mouse average Endo-DA count influence and Endo-DA entropy influence (Pearson r = 0.69 computed from model predictions on leave-two-out held-out data; P = 0.001, P-value computed via one-sided shuffle test). Shading indicates the 95% bootstrap confidence interval. c, Scatter plot (including regression line) of per mouse average Opto-DA learning versus Endo-DA count influence (Pearson r = 0.51 (computed from model predictions on leave-two-out held-out data); P = 0.001, P-value computed via one-sided shuffle test). Shading indicates the 95% bootstrap confidence interval. d, Top, the distribution of per syllable average Endo-DA count influence (n = 296 mouse–syllable pairs). Bottom, Opto-DA learning plotted syllable-by-syllable for ‘learner’ mice (n = 9 mice). e, Top, average Endo-DA count influence across syllable categories. Bottom, average Opto-DA learning across syllable categories. f, Top, scatter plot (including regression line) of catch trial syllable-associated dLight and Opto-DA learning for each mouse–syllable pair (r = 0.32 over held-out data; P < 0.001, estimated via one-sided shuffle test). Bottom, model performance (evaluated with five times fivefold cross-validation) using actual versus shuffled data. g, Hypothesis that evoked dopamine release combines with ongoing endogenous release to alter behavioural choices. h, Model-based likelihood of predicting held-out syllable choices on Opto-DA stim experiments (blue) relative to control models (Methods) (P = 7 × 10−18 across all model comparisons relative to dLight model, U = 2,500, f = 1, two-sided Mann–Whitney U test; n = 50 model restarts; Methods). The right y-axis indicates the model performance as a fraction the of maximum correlation. i, The relationship between average model accuracy (correlation between predicted syllable usage and actual usage) and the ‘extra dopamine’ free parameter (black). Shading indicates the 95% bootstrap confidence interval. The distribution of empirically measured optically evoked dLight fluorescence is shown in blue.
