Mapping nerve changes in the hippocampus to behaviour changes during Alzheimer’s

Research project: An electrophysiological and computational analysis of hippocampal synaptic changes in the Alzheimer's disease mouse in vivo.

Lead Investigator: Dr John Gigg

Institution: University of Manchester

Grant type: PhD

Duration: 3 years

Amount: £75,000

What was the project, and what did the researchers do?

Nerve cells rely on good communication between themselves to stay healthy. We know that this communication is disrupted in Alzheimer's disease, although the mechanism is poorly understood. It is thought that the accumulation of two hallmark Alzheimer's proteins, called amyloid and tau, interferes with communication signals within and between nerve cells.

The PhD student on this project, Daniel Squirrell, measured electrical impulses in the brains of mice that showed symptoms of Alzheimer's disease. By looking at a region of the brain which experiences damage early in Alzheimer's called the hippocampus, the team aimed to map how changes in the brain cell networks related to the behaviour of the mice. To do this they stimulated certain nerve cells and monitored how the messages are passed on to other cells, then analysed them with unique complex algorithms developed by Dr Gigg.      

What were the key results and how will this benefit people with dementia?

The researchers found that the hallmarks of Alzheimer's disease did have an effect on the ability of the nerve cells in parts of the hippocampus to communicate with each other. These findings were related to the inability of the mice to store memories, a feature also seen in people affected by dementia. 

These findings shed new light on the early changes in brain cells that affect the ability to store memories. An increased understanding of the complex activity of brain cells in the earliest stages of the disease will shed light on the processes behind Alzheimer's disease development. It also provides a target area of the brain for researchers to focus on when finding ways to combat the condition. 

What happened next? Future work and additional grants

Dr Gigg is fostering collaborations with other Alzheimer's disease researchers to more fully understand how the brain changes at the cellular level in the condition, particularly focusing on the role of the immune system.

How were people told about the results? Conferences and publications

Publications:

Several publications are in preparation for submission to peer-reviewed journals, including:

Synaptic hypo-excitability in the subiculum of the 3xTg mouse model for Alzheimer's disease in vivo. 

Deficient information transfer during slow-wave ripples in the 3xTg model for Alzheimer's disease. 

Conferences:

The findings were presented at research meetings for both Alzheimer's Society and ARUK, including the Alzheimer's Society's Research conference in 2015. 

The findings have also been presented at several international and national scientific conferences, including the 2013 Spring Hippocampal Conference (Taormina, Italy), the 2014 European Brain and Behaviour Society annual meeting (Munich, Germany) and the 2014 annual meeting of the Federation of Neuroscience Societies (FENS; Milan, Italy). 

Dr Gigg has also given presentations of the work at several UK universities, including invited seminars at the University of Edinburgh (2014 and 2015) and The University of Nottingham (2015).

Dr Gigg also presented on the theme of Alzheimer's Disease at the public engagement event 'Pint of Science' in Didsbury, Manchester in May 2015.

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