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