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The neurobiology of schemas: knowledge acquisition and consolidation

Final Report Summary - NEUROSCHEMA (The neurobiology of schemas: knowledge acquisition and consolidation)

The primary aim of NEUROSCHEMA was to learn more about the brain mechanisms of “knowledge” acquisition. Neurobiological insights could include where different forms of knowledge are represented in the brain, how we add new knowledge to existing knowledge structures (“schemas”), and how the acquisition and retention of new knowledge proceeds. The project was inter-disciplinary– including work on both human and animal subjects. It spanned the basic research-translational divide, with some research aimed at understanding neural mechanisms and other projects of an applied nature (in an educational setting). This inter-disciplinarity was reflected in the skills of the two teams of Postdoctoral Scientists and Ph.D students– ranging from neurophysiologists and molecular biologists to experimental psychologists and behavioural scientists. The incorporation of some translational work was motivating for the whole group, as it gave a sense that we were doing work that could not only be reported as academic papers, but might also have a more direct impact in educational settings.

The key scientific achievement in the animal neuroscience domain (Edinburgh) was the discovery that activity in the noradrenergic locus coeruleus (LC) region of the brain, an important neuromodulatory region, was critical for the previously discovered role of novelty in augmenting the retention of recently formed associative memories (Takeuchi, Duszkiewicz et al, Nature 2016; Wang et al, Proc Natl Acad. Sci. 2010). This research involved the synergistic application of behavioural, pharmacological, electrophysiological, anatomical and optogenetic tools. We also made the paradoxical observation that, although the LC is noradrenergic, these neurons may co-release dopamine in the hippocampus. This finding has led to a flurry of interest since the paper was published. A second major achievement was our finding that, in a prominent animal model of Alzheimer’s Disease, it is possible to observe faster forgetting over time (i.e. a failure of memory retention), at a stage of development prior to the deposition of overt neuropathology (Beglopoulos et al, Nature Communications, 2016).

Those in the human neuroscience domain (Nijmegen) include the findings of a series of studies probing human brain-system-level processes identifying the medial prefrontal cortex as a connecting hub interacting with the medial temporal lobe and posterior neocortex, in particular the angular gyrus. Parametrically increasing congruency between new information and existing knowledge was found to be associated with medial prefrontal encoding processes at the cost of medial temporal processes (van Kesteren et al., Neuropsychologia 2013). This balance between medial prefrontal and medial temporal encoding processes appears important for knowledge acquisition at university. Individual differences in medial prefrontal correlates of knowledge acquisition are predicting real-world study success at university (van Kesteren et al., Journal of Cognitive Neuroscience 2014). We also developed a paradigm conceptually linked to rodent studies and show that retrieval of schema-defining associations is related to activity along medial prefrontal cortex and angular gyrus (van Buuren et al., Journal of Neuroscience 2014). We found that performing exercise four hours after encoding improved memory retention over 48 hours and strengthened memory representations as assessed by multi-voxel-pattern analysis compared to the no-exercise control group (van Dongen et al., Current Biology 2016).