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Alzheimer’s disease : pushing the frontier of in vivo neuroimagining

Stéphane bancelin

Nationality French

Year of selection 2017

Institution Université de Bordeaux

Country France

Risk Health

Post-Doctoral Fellowship

2 years

30000 €

The elucidation of how memory formation happens in the brain is one of today’s biggest challenges in biomedical research. Success in the fight against neurodegenerative diseases, such as Alzheimer’s (AD), is conditional on acquiring this fundamental knowledge. Let’s remember that 50 million people worldwide are affected by dementia, and that there are nearly 10 million new cases every year. One of the main reasons the mechanisms underlying memory remain partly obscure is the limited spatiotemporal resolution of existing optical techniques. « Our view of the dynamics at play remain woefully fragmentary », as Dr. Stéphane Bancelin, from the Interdisciplinary Institute of NeuroSciences (IINS) in Bordeaux, explains. To remedy this problem, the researcher is working on an innovative super-resolution microscopy approach to enable live-cell observation of memory processes at the nanoscale. Specifically, his project focuses on changes happening to key components of neuronal communication : dendritic spines.

In the brain, information from one neuron flows to another neuron across a synapse. In the hippocampus, the archetypical memory center of the brain, neurons receive this synaptic input via tiny protrusions called dendritic spines. « These structures dynamically regulate synaptic transmission and, predictably, dysfunctional spines are involved in some of the most prevalent brain diseases such as AD », the head of the project summarizes. Indeed, it has been speculated that the morphological plasticity of dendritic spines is important for learning and memory, but the molecular mechanisms involved remain mysterious. « Our aim is to be able to visualize hippocampal spines in vivo through a cranial window and to look at how their structure changes during memory acquisition ».

Uncovering the role of dendritic spines in learning and memory impairments

But first, Dr. Stéphane Bancelin’s team needs to establish a new optical paradigm based on super-resolution microscopy. Leveraging on recent advances, they are developing an adaptive approach for super resolved live-cell imaging of a deep brain area based on a state-of-the-art technique called STED (Stimulated Emission Depletion) microscopy. « That’s the most crucial and trickiest part, says the researcher. MRIs, scanners and EEGs are great if you want to look at actions taking place in the brain, but they don’t provide high enough resolution to observe neurons one at a time ». Once the technique is operational, the plan is to perform chronic imaging sessions on mice with and without AD. The morphology and turnover of dendritic spine in the hippocampus will be studied and investigated with the aim of correlating structural changes with memory formation and impairment.

Uncovering the processes that govern information throughout the brain is the cutting edge of modern neuroscience. By pushing the frontiers of neuroimaging, the present project will make a significant contribution towards a better understanding of the mammalian brain, « its uniquely complex and dynamic anatomical organization, (…) like a supercomputer and the Library of Congress rolled into one », as the main investigator puts it. As for his investigation of memory formation in the hippocampus, the output aims to help earlier diagnosis of Alzheimer’s disease and the identification of new therapeutic targets.