Uncovering the nanoscale underpinnings of cognitive decline
Even in the healthy brain, ageing is commonly associated with cognitive decline. The factors that could explain large inter-individual differences in the progression of the decline are still poorly understood. In this project, we propose to use a multidisciplinary strategy, including behavioral tests, optical microscopy, electrophysiology, and artificial intelligence, to investigate how synapses reorganize in aged animals with varying levels of cognitive impairment. Super-resolution microscopy will provide the required spatial resolution to resolve synaptic nanodomain that regulate neuronal function and molecular interactions in the brain.
We will examine how changes in the synaptic nanoarchitecture are related to variations in neuronal activity and how this could be linked to the observed cognitive decline. We hypothesize that an imbalance towards inhibitory synaptic activity is linked to the remodeling of synaptic structures at the nanoscale in animals showing increased cognitive impairments. Machine learning approaches will be integrated to analyse the detailed cartography of synaptic structures obtained with the proposed bioimaging approach.
We will address two main objectives: 1) understand how changes in the way synapses are organized (specifically when comparing excitatory and inhibitory synapses) are related to age-related cognitive decline, and 2) further develop bioimaging techniques enabling the characterization of how structural changes impact synaptic activity. The project, which is at the interface between neuroscience, microscopy, and artificial intelligence, aims at detecting detect subtle changes in synaptic structure and function in cognitively impaired animals. It could be a first step in understanding how synaptic remodelling affect cognitive abilities and could lead to the development of preventive approaches targeting synaptic health.
Flavie Lavoie-Cardinal , Université Laval
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