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Computational modelling identifies key determinants of subregion-specific dopamine dynamics in the striatum.

2026-01-23, eLife (10.7554/eLife.105214) (online)
Trevor W Robbins, Freja Herborg, Aske Lykke Ejdrup, Ulrik Gether, Jakob Kisbye Dreyer, Matthew D Lycas, Søren H Jørgensen, and Jeffrey Dalley (?)
Striatal dopamine (DA) release regulates reward-related learning and motivation and is believed to consist of a short-lived and continuous component. Here, we build a large-scale three-dimensional model of extracellular DA dynamics in dorsal (DS) and ventral striatum (VS). The model predicts rapid dynamics in DS with little to no basal DA and slower dynamics in the VS enabling build-up of DA levels. These regional differences do not reflect release-related phenomena but rather differential dopamine transporter (DAT) activity. Interestingly, our simulations posit DAT nanoclustering as a possible regulator of this activity. Receptor binding simulations show that D1 receptor occupancy follows extracellular DA concentration with milliseconds delay, while D2 receptors do not respond to brief pauses in firing but rather integrate DA signal over seconds. Summarised, our model distills recent experimental observations into a computational framework that challenges prevailing paradigms of striatal DA signalling.
This article is included in 1 public curation:

Basal Ganglia Advances
 
 
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