The consequences of a neurotransmitter-induced opening of a postsynaptic ion channel are relatively well known; the membrane conductance changes, and the intracellular voltage moves towards a new equilibrium. However, when G protein-coupled receptors are activated the intracellular cascades that may be generated are ‘Legion’. A variety of chemical chain reactions can occur that depend on the type of G protein activated, and in only a few cases is the final action on the neuronal membrane conductance. For example, in striatal neurons the action of dopamine on G protein-coupled receptors has little immediate electrophysiological consequences, but loss of dopamine causes parkinsonism. The use of an exciting technical development to display the intracellular cascades in single neurons after dopamine receptor stimulation is presented in this issue (Castro et al. 2013). A genetically encodable ‘A-kinase activity reporter’ (AKAR3) protein was used. AKAR3 is a long protein construct composed of a phosphoamino acid binding domain and protein kinase A (PKA)-specific substrate with the addition, at both ends, of fluorescent proteins. When phosphorylated by PKA, the phosphoamino acid domain changes to a conformation that leads to an increase in ‘fluorescence resonance energy transfer’ (FRET; Allen & Zhang, 2006). So far, these reporters have mainly been used in primary cultures or in cell lines where strong responses to β2-adrenergic receptors are recorded. In slices, the technique has the disadvantage of an overnight incubation to allow the penetration of the viral vector and protein expression (Gervasi et al. 2007). However, it allows real-time monitoring of PKA activation with a two-photon scanning microscope. Castro et al. (2013) have extended the use of AKAR3 to brain tissue slices from either cortex or striatum. The same group has already published on the activation of β-adrenergic receptors in cortical slices, where type 4 phosphodiesterase inhibition leads to large increases in signal (Castro et al. 2010). In striatal neurons, not only are the signals very much higher anyway (e.g. the less sensitive Epac1-camps is adequate to see the change in cAMP after dopamine) but the responses of AKAR3 are also larger and faster than in cortical neurons. The dissimilar responses between striatum and cortex could be the result of the differences in dopaminergic innervation density in the two structures. Perhaps postsynaptic actions are regulated to match the presynaptic input. A possible mechanism for the differences in striatal versus cortical responses could rest on the histochemical marker for striatal neurons, DARPP-32 (Walaas et al. 1983). DARPP-32 strongly inhibits protein phosphatase-1, which is the same protein that terminates the AKAR3 signal. Bursts of action potentials initiated in dopamine-containing neurons result in dopamine being released in short pulses onto postsynaptic targets. Dopamine released in this fashion may signal the success of predictions about the outcomes of recent actions. Changes in striatal neuronal activity as a consequence of such brief pulses of dopamine have been the source of many theoretical papers about motor learning in the striatum, but the biochemical substrate of such actions has been elusive. The rapid response of the striatal cells reported by Castro et al. (2013) in this issue demonstrates in an elegant way that a 100 ms activation of D1 receptors is sufficient to produce a half-maximal PKA activation. On the contrary, cortical cells produce only a 20% activation with a stimulus 10 times longer. In addition, the authors show that there are downstream effects to such PKA activation, because similar short pulses of dopamine activate the immediate early gene c-fos in striatal neurons. The numbers of FRET biosensors of phosphorylation have been expanding recently; because there are many kinases potentially active in neurons, this development points to interesting future explorations of the intracellular consequences of receptor activation and their effects on neuronal circuitry. However, there may be more than 500 proteins that can be phosphorylated by PKA alone, and so the answer to what is finally changed by receptor activation seems likely to remain, at least for now, ‘my name is Legion, because we are very many’. However, like the pigs in the biblical tale, candidates are rapidly eliminating themselves and so we may have a better answer before too long.