Plain wording

D1 receptor occupancy trails extracellular dopamine by about 50 milliseconds and rises only during bursts, not tonic firing.

slug d1r-tracks-da-50ms-delayrole empiricalpanel fig1H, fig1I

Every simulation starts D2 occupancy at a value the model's own parameters do not predict, with no test of how much it matters.

slug d2r-initialization-unjustifiedrole methodologicalpanel fig1H

A full one-second pause in firing barely lowers D2 receptor occupancy, across a tenfold range of assumed D2 affinity.

slug d2r-insensitive-to-brief-pausesrole empiricalpanel fig1J

D2 receptor occupancy takes seconds to fall back after a burst, so it cannot separate closely spaced bursts.

slug d2r-integrates-over-secondsrole empiricalpanel fig1H

During pacemaker firing, D2 receptor occupancy is higher in ventral than dorsal striatum, matching the higher tonic dopamine.

slug d2r-occupancy-higher-in-vsrole empiricalpanel fig2G

Super-resolution imaging shows the dopamine transporter is more nanoclustered in ventral than in dorsal striatum.

slug dat-clustering-greater-in-vsrole empiricalpanel fig4M, fig4N

Dopamine transporter protein is more abundant in dorsal than ventral striatum, matching the uptake-rate ratio the model assumes.

slug dat-immunostaining-dorsoventral-gradientrole empiricalpanel fig2—supplement 1B, fig2—supplement 1C

Dense transporter nanoclusters clear dopamine about twice as slowly as evenly spread ones, because dopamine runs out around them.

slug dat-nanoclustering-slows-clearancerole empiricalpanel fig4C, fig4D, fig4E, fig4F, fig4G

During pacemaker firing, dorsal striatum holds separate dopamine hotspots with much of the volume empty, not a tonic baseline.

slug ds-lacks-pervasive-tonic-darole empiricalpanel fig1D, fig1E, fig1F

The three-to-one dorsal-to-ventral ratio of transporter uptake capacity is taken from prior literature, not measured here.

slug ds-vs-vmax-ratio-assumedrole scopepanel fig2A (implied throughout)

Simulated voltammetry reproduces published recordings where ventral striatum peaks higher than dorsal at every frequency.

slug fscv-matches-may-wightman-1989role empiricalpanel fig2E

D1 receptors detect brief dopamine bursts while D2 receptors integrate dopamine over seconds, because their kinetics differ.

slug hypothesis-d1-d2-temporal-distinctionrole hypothesispanel hypothesis

Packing transporters into dense nanoclusters lowers their effective uptake capacity even with total transporter unchanged.

slug hypothesis-nanoclustering-regulates-vmaxrole hypothesispanel hypothesis

Dorsal hotspots versus ventral tonic coverage follow from the difference in uptake capacity, not from how dopamine is released.

slug hypothesis-vmax-explains-regional-differencerole hypothesispanel hypothesis

Earlier voltammetry work established that dopamine uptake capacity is roughly three times higher in dorsal than ventral striatum.

slug interprets-cragg-rice-vmax-ratiorole literature-contextpanel fig2A (implied parameterization)

May and Wightman found in rat slices that ventral striatum reaches higher evoked dopamine peaks than dorsal at every frequency.

slug interprets-may-wightman-1989-fscvrole literature-contextpanel fig2E (explicit replication comparison)

Short low-frequency bursts keep dopamine inside the burst zone, while stronger bursts spill it into a far larger volume.

slug low-burst-no-spillover-high-burst-doesrole empiricalpanel fig1G

The nanoclustering simulations hold total uptake capacity fixed, so slower clearance would not follow if clustering added DAT.

slug nanoclustering-constant-vmax-constraintrole scopepanel fig4C, fig4D, fig4E, fig4F

The nanoclustering work uses a separate tiny-scale model never coupled back to the tissue-scale model of the other figures.

slug nanoclustering-model-varicosity-scalerole scopepanel fig4C, fig4D, fig4E, fig4F

VMAT2, which loads dopamine into vesicles, shows no dorsoventral gradient, so release capacity cannot explain the difference.

slug vmat2-gradient-absentrole controlpanel fig2—supplement 1A, fig2—supplement 1B, fig2—supplement 1C

Ventral striatum, running closer to transporter saturation, shifts its tonic dopamine far more than dorsal when uptake changes.

slug vmax-modulation-larger-impact-in-vsrole empiricalpanel fig3K

Of all the parameters swept, only uptake capacity affects dorsal and ventral striatum differently, the rest moving both alike.

slug vmax-only-parameter-driving-regional-differencerole empiricalpanel fig3B, fig3C, fig3E, fig3F, fig3G, fig3K, fig3L

Ventral striatum with a twentieth of its terminals active spreads dopamine as widely as dorsal striatum with all of them active.

slug vs-low-active-fraction-resembles-ds-distributionrole empiricalpanel fig3B

Even the lowest-concentration parts of ventral striatum stay above ten nanomolar dopamine during pacemaker firing.

slug vs-lowest-percentiles-above-10nmrole empiricalpanel fig2D

With its lower uptake capacity, ventral striatum fills the whole simulated volume with diffuse tonic dopamine, not hotspots.

slug vs-maintains-pervasive-tonic-darole empiricalpanel fig2A, fig2B, fig2C