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

• DOI: 10.7554/elife.105214
• Publication Date: 2025-02-17T15:25:12Z
• Authors: Aske L Ejdrup; Jakob K Dreyer; Matthew D Lycas; Søren H Jørgensen; Trevor W Robbins; Jeffrey W Dalley; Freja Herborg; Ulrik Gether
• Keywords: Dynamics

Striatal dopamine (DA) release regulates reward-related learning and behavioural activation is believed to consist of a short-lived phasic continuous tonic component. Here, we build three-dimensional model extracellular DA dynamics in dorsal (DS) ventral striatum (VS) that include tens thousands sites. The predicts rapid DS with little-to-no basal DA, much slower the VS enabling build-up level. These regional differences do not primarily reflect different phenomena but rather arise from differential transporter (DAT) activity. Interestingly, our simulations posit prevalent nanoclustering DAT as possible regulator this Receptor binding show D1 receptor occupancy follows concentration millisecond delay, while D2 receptors integrate signal over seconds. Summarized, distills recent experimental observations into computational framework challenge prevailing paradigms striatal signalling.