FOR 5159:  Resolving the prefrontal circuits of cognitive flexibility

• Subject Area: Medicine
• Term: since 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437610067

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 und 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? Do the lack of stereotyped specialization or the connectivity patterns in PFC account for flexibility? Are the neural codes 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 aims to understand how prefrontal circuits code aspects of cognitive flexibility (i.e. working-memory and decision-making). The working hypothesis is that 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. To foster efficient binding of conceptual and methodological expertise within the consortium, common work packages (and corresponding co-worker exchange) between labs are defined in each project. On a medium- to long-term scale the Research Unit will identify the neuronal mechanisms, which control behavioral flexibility across species and life span (1st funding period) and will elucidate the link between circuit miswiring and disease-relevant cognitive deficits (2nd funding period).

• DFG Programme: Research Units
• International Connection: Austria, USA

Projects

• Choice-predicting neurons in the prelimbic cortex during a modified Iowa-gambling-task for rats (Applicant Klausberger, Thomas )
• Coordination Funds (Applicant Hanganu-Opatz, Ileana L. )
• Deciphering dynamic and stable prefrontal representation of memory contents in mice (Applicants Bartos, Marlene ;  Sauer, Jonas-Frederic )
• Intrinsic determinants of flexible prefrontal ensembles (Applicant Leibold, Christian )
• Local circuit and projection based prefrontal response diversity for action control in rats (Applicant Diester, Ilka )
• Maturation of flexible cognitive behavior as result of age-dependent formation of prefrontal ensembles in juvenile mice (Applicant Hanganu-Opatz, Ileana L. )
• Neural basis of deduced ordinal judgments in the primate prefrontal cortex (Applicant Nieder, Andreas )
• Neuro-dynamic mechanisms of cognitive flexibility at the cellular and microcircuit-level in human dorsolateral prefrontal cortex (Applicant Jacob, Simon N. )
• Reconstructing neuro-dynamical principles of prefrontal cortical computations across cognitive tasks and species (Applicant Durstewitz, Daniel )
• Resolving the diversity of prefrontal neuron activity within and across behavioral tasks in mice (Applicant Sigurdsson, Torfi )

• Spokesperson: Professorin Dr. Ileana L. Hanganu-Opatz