, 1979; Fletcher et al., 1999; Grottick et al., 2000), there are many types of serotonin receptor that have an excitatory net effect on dopamine (Alex and Pehek, 2007; Boureau and Dayan, 2011). In fact, an excitatory effect would actually be appropriate in some circumstances if the account about safety signaling is correct, as dopamine should respond

to the prospect of future safety engendered by the serotonergic report of possible aversion. Distinctions such as this may provide a route for helping understand part of the multiplicity of serotonin receptors (Cooper et al., 2002; Hoyer et al., 2002). As mentioned, whether the safety is achievable depends on the RG7204 cell line degree of controllability of the environment (Maier and Watkins, 2005; Huys and Dayan, 2009); how controllability is represented JQ1 mouse is not clear. In terms of the asymmetry, dopamine appears not to exert nearly such strong effects on 5-HT as vice-versa. Finally (K), a complex tapestry of heterogeneity is revealed, particularly within the serotonin system. We have also noted substructure in the dopamine system such as the mesocortical

dopamine neurons that are excited rather than inhibited by punishment (Brischoux et al., 2009; Lammel et al., 2011). Neuromodulatory representations of utility appear to play a central role in habitual control, not the least by controlling learning directly. Since goal-directed control is based more on predictions of specific outcomes, one might expect different neuromodulatory issues to arise. Indeed, there is direct evidence that dopamine plays little role in evaluation in the goal-directed system (Dickinson et al., 2000). Nevertheless, it can still influence the vigor of the execution of the responses which it mandates

(Palmiter, 2008). We noted that goal-directed Endonuclease (Dickinson and Balleine, 2002; Balleine, 2005) or model-based (Daw et al., 2005; Doya, 2002) control exhibits fuller flexibility in the face of factors such as changes in motivational state. This requires that the utility of predicted outcomes can be assessed under the current motivational state. In turn, this suggests a role for direct and/or indirect neuromodulatory influences over neural structures such as gustatory insular cortex or possibly the basolateral nucleus of the amygdala involved in such evaluation (Balleine, 2005, 2011) as providing information about that state. However, although we may be able to predict the values of some outcomes under expected future motivational states, there appear to be definite limits to such predictions (Loewenstein and O’Donoghue, 2004), perhaps because of constraints on the subjunctive determination of neuromodulatory state. This would limit any such prospective somatic marker (Damasio, 1994).