, 2009). Instead, OFC and amygdala may be best understood as comprising at least two neural subsystems—an appetitive system and an aversive system—which exhibit different temporal dynamics. These dynamics may have arisen out of evolutionary pressure to rapidly detect and respond to threats, or selleck compound to approach potential new rewards with caution. One distinctive role for OFC may come into play only after learning about reinforcement contingencies. After learning, we found that OFC neurons consistently signal impending reinforcement more rapidly than amygdala. This may reflect the primary role of PFC in executive functions and emotional regulation with regard to both rewarding

and aversive experiences. Consistent with this idea, Granger causality analysis of LFP signals suggests a greater influence of OFC processing on amygdala than the opposite, an effect that emerges with learning. This effect was especially prominent in the beta frequency band, which has been suggested to be well suited for long-range interactions between brain areas (Kopell et al., 2000). Importantly, despite the directional effect, the analysis of LFP data suggests continuous and dynamic reciprocal interactions between OFC and amygdala during task engagement. We note that this finding does not exclude the possibility that a third brain area—such as another area of PFC—could influence both OFC and amygdala

in a consistently asymmetric manner. Likewise, these findings do not preclude the participation of other brain areas in reversal learning. The striatum is a major output target for both OFC and amygdala (Carmichael and Price, 1995, click here Fudge et al., 2002 and Haber et al., 1995), and thus a likely site of interaction and integration of signals from the

two brain areas. The striatum itself contains neurons that signal changing reinforcement contingencies during instrumental tasks (Brasted and Wise, 2004, Pasupathy and Miller, 2005 and Tremblay et al., 1998), and one study reported that signals update even more rapidly in striatum than in PFC upon repeated reversals of the visuomotor reinforcement contingencies associated with familiar stimuli (Pasupathy and Miller, 2005). This raises the possibility that as stimulus sets and their associated Megestrol Acetate possible reinforcements upon reversals become increasingly familiar, the striatum may assume a more prominent role in directing adaptive behavioral responses to the changing environment. Our results indicate that reversal learning likely involves complex interactions between anatomically intermingled neural circuits spanning the amygdala and OFC, and perhaps other brain structures. Fully testing the predictions of the current work, however, may require the development of techniques that can specifically manipulate activity in appetitive or aversive neurons in targeted structures—in contrast to, e.g., inactivating the entire structure—during task performance.