This Co-Investigator Application is an interdisciplinary experimental analysis of the neurobiological mechanisms by which we acquire knowledge. Our approach builds on the foundations of contemporary cognitive neuroscience, particularly ideas about the neural mechanisms of declarative memory, and upon recent findings of the participating laboratories (Morris, Fernández) that have each addressed key issues associated with the rapid acquisition and assimilation of new associative information into existing neural ¿schemas¿. Rapid learning depends upon both novelty and prior knowledge. We propose a coordinated program of research concerning the mechanisms of both determinants. First, we will test that novelty, acting via the release of dopamine, has a direct impact on the mechanisms of cellular consolidation in the hippocampus. Second, with respect to prior knowledge, the retention of new event-related associative information requires the process of systems consolidation within declarative memory, as widely studied, but we further suggest that the organisation of knowledge requires more than just stabilising memory traces within neocortical networks. It also involves the integration of distinct memory traces into neural ¿schemas¿ that, once formed, have a major positive influence on future learning. Our experiments to date are supportive and we outline new research to examine the neurobiological basis of schemas. This will involve animal experimentation including novel behavioural tasks, optogenetics and single-cell recording; and functional magnetic resonance imaging of the human brain using new cognitive tasks combined with pharmacology, transcranial magnetic stimulation, model-free analysis methods, and a translational project reaching into real-world education.