Completed Brain & Nervous System Psychology & Behaviour

Physiopathology of brain-wide assemblies in adaptive memory

Funder MRC (part of UKRI)
Recipient organisation
Funding £2.3M
Period Mar 2020 — Mar 2026

In plain English

AI plain-English summary

Every decision we make draws on past experience, but the brain coordinates that memory across many regions at once—and when that coordination fails, memories become maladaptive. The hippocampus has long been known to host “cell assemblies” that link memory to behaviour, but real-life memories involve multiple brain areas processing different types of information simultaneously. How these distributed cell activities combine to form a rich, coherent memory remains poorly understood. This gap matters because breakdowns in cross-region communication are thought to underlie cognitive decline in ageing and in neurological or psychiatric conditions. The research will map the mechanistic rules by which distributed cell assemblies support complex memories, then test two specific failure modes: the re-emergence of extinguished drug-seeking behaviour driven by cross-region signals, and the neural basis of inferential reasoning—the ability to logically connect information never experienced together. This is fundamental science. It will not produce a therapy or diagnostic tool in the short term. But by revealing how the brain normally integrates memory across regions, and how that integration breaks down in maladaptive states, it aims to provide principles for future interventions that could harness or correct memory-related brain activity.

View original technical description
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.

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Researchers

David Dupret (Principal Investigator)

Related Research

Grants with similar aims, by meaning.

Dynamics of cell assemblies underlying adaptive and mal-adaptive memories
Decoding neural assemblies over multiple brain regions, extended experience and sleep-wake cycles
Circuit and cellular analysis of the lateral entorhinal cortex in associative recognition memory
Optimising neuronal plasticity for associative memory
Neural mechanisms of memory & prediction, finding structure in experience

Original classification

Intramural

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.