Physiopathology of brain-wide assemblies in adaptive memory

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When making decisions, we often draw on previous experience. This ability to inform behaviour from memory relies on the fine-grained coordination of activity between nerve cells in the brain. The hippocampus is a region of the mammalian brain where the activity of such “cell assemblies” has been related to memory-guided behaviour. However, memories of important life events are expected to span multiple brain regions, with each region processing a particular dimension of information. This organisation of information representation could be at the heart of the complexity of the cognitive disabilities associated with natural ageing and certain neurological/psychiatric diseases. Here, we will first seek to provide a comprehensive mechanistic explanation of how cell activities distributed across multiple brain regions support complex, detail-rich memories. In this work, we will further consider unwanted memories related to drugs of abuse that underpin maladaptive responses, investigating how cross-brain-region communication drives the re-emergence of behaviourally-extinguished drug memory. We will finally identify brain mechanisms of inferential reasoning, a higher-order operation that allows individuals to deduce logical links between sets of information that have not been experienced together. This work is intended to provide principles of interventions to harness brain physiopathology of maladaptive memory.