Organising knowledge for flexible behaviour in the prefrontal-hippocampal circuitry (360G-Wellcome-214314_Z_18_Z)

Humans and animals can find new solutions to existing problems, and generalise existing knowledge to new situations. This flexibility relies on internal models of the relationships and causes that govern our world. Despite the importance of world-models to a wide class of behaviours and thus likely relevance to psychiatry, little is known about how they are represented in the brain. Recent evidence suggests rapid progress can be made by comparison to the field of spatial cognition. Specific neuronal mechanisms are shared between spatial and non-spatial model-based behaviours, and new theories suggest links between spatial and non-spatial knowledge. We will study and manipulate hippocampal, entorhinal and prefrontal activity in rodents performing model-based tasks bridging spatial and non-spatial domains. Using unusually rich but precisely specified tasks, we will characterise neuronal representations of world models quantitatively, enabling formal mathematical description. We will therefore provide new data describing how internal-models are represented in neuronal activity in service of flexible behaviour, and how these representations generalise knowledge across different tasks. These data will be crucial for developing theories of how our brains represent and generalise knowledge for flexible behaviour, and will lay essential groundwork for studies of how these representations go awry in clinical populations.