Our environment is constantly changing. Successful survival under these conditions implies that our behavior has to be flexible as well. We experience different places and contexts, have to conduct different tasks in a rapid sequence and need to constantly develop and re-arrange acting strategies. These abilities are not inherited, but develop with age and their regression forms the core of several pathologies. It is commonly held that in mammalian species the prefrontal cortex (PFC) is the hub brain area accounting for the flexibility of minds (i.e. cognitive flexibility). A fundamental aim of neuroscience is to decipher the dynamic principles that govern the ability to cope with a permanently changing environment. However, experimental achievement of this aim has proven notoriously difficult, since appropriate methods to monitor and selectively manipulate the activity of single neurons or neuronal ensembles in behaving animals were lacking. The impressive technological and analytical development during the last years enables now to address crucial questions: Which neuronal underpinnings control cognitive flexibility? Does the lack of stereotyped specialization or the connectivity patterns in PFC account for flexibility? Are the neural codes and computational mechanisms of flexibility common across mammalian species despite the apparent lack of prefrontal homology?

In a coordinated and interdisciplinary research effort spanning complementary research expertise in different species, concepts, and methodologies, the Research Unit 5159 “Resolving the prefrontal circuits of cognitive flexibility” aims to understand how prefrontal circuits code and compute well-defined aspects of cognitive flexibility (i.e. working memory and decision making). The working hypothesis is that, for these abilities, neuronal ensembles in functionally homologous areas of PFC from different species are formed through temporal coordination defined by outputs and inputs. Experimental results from similar monitoring and manipulation of prefrontal circuits will be integrated into computational models with the aim of revealing overarching neuro-dynamical principles of cognitive flexibility that are common to rodents, monkeys, and humans, on the one hand, and the species-specific specialization of prefrontal coding, on the other hand”