Unbiased Analysis of Excitatory Synaptic Connectivity in the Aging Cerebral Cortex
Description: Understanding the structural changes underlying the cognitive decline during aging has occupied neuroscientists for many years. They have relied on light and electron microscopy to understand the extent to which morphological alterations may correlate with functional deficits This decline is believed to reflect changes to the neural circuits and in particular the synaptic connections. However, existing studies have only involved either small sample areas or specific neuronal types. As a result, they have produced apparently conflicting results for different brain regions with regards to the connectivity between neurons while a comprehensive volume analysis of the aging-induced changes through the different layers of a defined region of cortex is still missing.The goal of this project is therefore to remedy this using a 3D electron microscopy imaging approach along with Computer Vision algorithms free of human bias to compare the structure of synaptic contacts, dendritic spines, and synaptic vesicle pools. This will allow us to analyse the age related synaptic changes in each layer of a single column of the cerebral cortex. This will provide important data about the fundamental elements involved in synaptic connectivity in each layer of a single cortical column. It will also show how these elements change as a result of aging. Finally, it will establish a high throughput workflow for unbiased analysis of cortical connectivity and organelle organisation. This workflow will be applicable across a number of research fields, ranging from characterizing different brain regions to exploring how sensory stimuli and behaviours shape neuronal and synaptic morphology.
Amount: CHF 369,000
Funding type: research
Funder scheme: Project funding
Start date: 2017-09-01
End date: 2020-08-31
Investigator: Knott, Graham
Institution: EPF Lausanne – EPFL
Funded outputs count: 3
Funder award ID: 170082
OpenAlex ID: G5584846495