Extended Data Fig. 6: Ablating the Ca²⁺ sensor Syt-1 in dopamine neurons does not disrupt in vivo dopamine dynamics or locomotor behaviors.

a–c, Analyses of motor behaviours as in Extended Data Fig. 1u–z, but for Syt-1 control and Syt-1 cKO^DA mice. For dopamine release analyses in Syt-1 cKO^DA, see⁴¹. The time spent to cross a horizontal bar (a), to climb down a vertical bar (b), or the latency to fall from a rotarod after four days of training (c) are quantified, Syt-1 control 10 mice, Syt-1 cKO^DA 10. d–i, In vivo fibre photometry performed as in Fig. 2 and Extended Data Fig. 3, but for Syt-1 cKO^DA mice with example traces (d) and quantification of variation of ΔF/F₀ of GRAB_DA (e) and of tdTomato (f) fluorescence before and after i.p. injection of the D2 receptor antagonist haloperidol (2 mg/kg), and with individual (event heatmaps, top) and average (bottom) time courses of GRAB_DA (g) and tdTomato (h) fluorescence aligned to the sensory stimulation (dashed line) and peak GRAB_DA per mouse (i). Event heatmaps are sorted by the peak GRAB_DA amplitude in g; Syt-1 control 200 events from 4 mice, Syt-1 cKO^DA 200/4. Altogether, knockout of Syt-1 from dopamine neurons did not disrupt motor function. Despite the strong impairment in dopamine release in brain slices^41,79, in vivo dopamine fluctuations were maintained, likely due to the remaining release after Syt-1 knockout, presumably asynchronous release⁸⁰, that is detected with in vivo microdialysis or in brain slices after dopamine transporter (DAT) blockade (striatum)⁴¹, or in response to stimulus trains (somatodendritic release)⁴⁴. Hence, removing the fast Ca²⁺ sensor from dopamine neurons does not suffice to abolish in vivo dopamine dynamics and Syt-1 cKO^DA mice cannot be used to test behavioural roles of these dynamics. Data are mean ± SEM; * p < 0.05, assessed by: two-sided Mann-Whitney rank-sum test for a, b, e, i; two-way ANOVA for c.