Memory dynamics: the cellular architecture of systems memory

Lead Research Organisation: University of Bristol
Department Name: Physiology and Pharmacology

Abstract

The human brain contains approximately 80 billion nerve cells (neurons). When you learn something new, which of those neurons will be involved in storing that information? Are all neurons equal, or are some more likely than others to store memories? Will a memory always involve the same neurons? Or will the memory trace (known as an 'engram') change over time, allowing you to file memories appropriately, remembering the important information and updating the engram with new knowledge?

These questions are all very challenging to answer. But if we do not answer them, we can never understand how the brain works, or how to treat memory disorders associated with illnesses such as dementia, depression and schizophrenia.

Over the past few years, technology has advanced to the point at which we can - at least in mice - "capture" the groups of neurons involved in learning a specific memory. These neurons are known as 'engram neurons', and were first discovered in a part of the brain called the hippocampus, which acts as a central indexing system for memory files in all mammals. We can activate engram neurons (to trigger recall of the memory) or silence them (to delete a memory). These methods have transformed our understanding of memory mechanisms over the past 2 years, but they are very new and evolving rapidly, as is out ability to measure brain activity from hundreds of neurons simultaneously.

In this 3-year series of experiments, we will combine capture of engram neurons with recording the activity from large populations of neurons in mouse hippocampus and connected brain regions to translate the algorithms used by engram neurons to learn, process and remember new information. This project would not be possible without the international team of neuroscientists involved, which spans the UK and Japan, uniting complementary expertise in genetics, psychology, computational analyses and electrical engineering.

We will also measure, for the first time, the activity of engram neurons during sleep. We have known for 2000 years that sleep supports healthy memory, but we still do not know precisely how. Now we have discovered engram neurons, the answers may be within reach.

Given that your entire personality and worldview are products of the many memory engrams stored by your brain, neuroscience of this type remains essential if we are to understand the fundamental biology of life and disease.

Planned Impact

This project aims to decipher the mechanisms through with the brain stores information in memory. Impacts of this work relate to Societal, Industrial, Clinical and Education domains. The key deliverables will include:

Society:
- Presentations and hands-on exhibits at neuroscience festivals in the UK and Japan, supporting public understanding of science and engaging school children in exploration of scientific methods and brain biology
- Art of science work, including working with choreographers and dancers to create a novel performance based around the nature of memory
- Media presentations on TV in Japan, the UK and the US, including work with a Hollywood actor interested in the basis of mood and memory

Industry:
- Collaborations with multinational pharmaceutical companies, supporting their efforts to design drugs that rescue memory impairments in dementias and psychiatric disorders
- Collaborations with medical devices companies, who design headsets capable of recording brain activity in the home and using sound stimuli to modulate brain waves during sleep and enhance memory

Clinical:
- Links to NHS memory clinics, who diagnose and treat patients suffering impaired memory, most notably Mild Cognitive Impairment (MCI) and Alzheimer's Dementia

Education:
- This project will provide opportunities to engage undergraduate and postgraduate students in the UK and Japan, giving seminars on state-of-the-art neurotechnology and exemplifying the value of international "team science"

Publications

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Title Neural activity-dependent gene delivery 
Description Transgenic mouse lines and viral vectors for labelling and control of neural activity in mouse brain 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact Experiments still in progress 
 
Description McHugh lab, RIKEN Brain Science Institute 
Organisation RIKEN
Department RIKEN Brain Science Institute
Country Japan 
Sector Public 
PI Contribution This is a UKRI-JSPS collaborative project. We have provided electrophysiological expertise and MATLAB code for data analysis
Collaborator Contribution The PDRA on this project spent 2 months in the host RIKEN lab in early 2020, running a series of experiments. RIKEN have also shared a range of viral gene delivery tools.
Impact Still data gathering.
Start Year 2019