Intracellular signaling with cyclic nucleotides are ubiquitous signaling pathways, yet the dynamics of these signals profoundly differ in different cell types. Biosensor imaging experiments, by providing direct measurements in intact cellular environment, reveal which receptors are activated by neuromodulators and how the coincidence of different neuromodulators is integrated at various levels in the signaling cascade. Phosphodiesterases appear as one important determinant of cross-talk between different signaling pathways. Finally, analysis of signal dynamics reveal that striatal medium-sized spiny neuron obey a different logic than other brain regions such as cortex, probably in relation with the function of this brain region which efficiently detects transient dopamine.