A person with Alzheimer’s disease can no longer remember where they put their keys or how to find their way home because the brain’s memory circuits have broken down at a fundamental level. This research tackles a specific gap in knowledge: scientists understand how individual brain cells (neurons) store memories at the molecular scale, and they can see large-scale brain activity on scans, but they do not know how the activity of many neurons working together actually produces a coherent memory of an event or a place. The team uses virtual reality to test spatial memory in both humans and animals, allowing direct comparison of how neurons fire when navigating a large, realistic environment. Because spatial memory loss is an early and prominent symptom of Alzheimer’s disease, understanding these neural mechanisms could provide new ways to monitor disease progression or identify targets for drug treatments. If successful, the work could also explain why traumatic memories in post-traumatic stress disorder become intrusive and disconnected from their original context. This is primarily fundamental science—it seeks to understand how the brain builds memories from the ground up. Past discoveries in this area have already led to memory-enhancing drugs and brain stimulation techniques; deeper knowledge could eventually improve those interventions.
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Our memories define who we are and the loss of day-to-day (or ?episodic?) memory, for example as a result of Alzheimer?s disease (AD), temporal lobe epilepsy or stroke, has a devastating impact on one?s capacity to live independently and places a huge burden on caregivers and the state. There is an enormous potential for memory to be improved, both in health and disease, via drugs (which modulate how neurons create and store memories), technological devices and memory strategies. However, our current level of understanding of memory processes means that we are a long way from being able to fully utilize these interventions. Critically, there is a gap between our understanding of memory processes at the level of molecules and cells (the neuronal level) through to the activity of populations of cells throughout the brain (the systems level). This research is aimed at bridging this gap by providing a detailed understanding of how the actions and interactions of neurons in the brain gives rise to memory. Much of the research focusses on spatial memory, where comparable data can be collected from animals and humans. By pioneering the use of virtual reality to test memory in realistic large-scale environments we have shown that similar neuronal representations are used by humans and animals to find their way around, and that it is possible to understand memory for where things are in terms of the actions of neurons within the brain. Because loss of spatial memory is a prominent and early feature of AD, the findings will be directly relevant to understanding and monitoring the progression of this disease. As well as being a challenge in its own right, understanding the basic neuronal mechanisms by which the brain remembers the spatial context of events, will also have knock-on effects for the progress of medical and therapeutic science. For one example, it can help us to understand how new memories are triggered when a novel event occurs, and how this might go wrong so that memories are lost, and how such loss might be avoided by drugs. For another example, we will test the idea that unwanted intrusive memories in posttraumatic stress disorder occur because the representations of the sights, sounds and feelings associated with a traumatic event have become disconnected with the representations of the specific context in which they occurred.
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