We have integrated models of receptor induced subcellular signaling into a quantitatively detailed neuron model of a striatal projection neuron to be able to investigate the underlying mechanisms of fast dopaminergic neuromodulation (Lindroos et al, 2018). In striatum, transient dopamine elevations play crucial roles when initiation of movements takes place. Behavioral effects are seen already within a couple of hundred milliseconds even though neuro- modulation typically affects membrane excitability via phosphorylation of ion channels. One model prediction made was that dopaminergic terminals likely activates excitatory ionotropic receptors, and indeed co-release of glutamate was recently found (https://doi.org/10.7554/eLife.39786.001) in this system.
The result is also illustrated in the form of a ‘live paper’ accessible via: https://www.humanbrainproject.eu/en/brain-simulation/live-papers/