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Synaptome architecture of the single neuron

Project description

The architecture of brain synapses

Synapses form a remarkably complex 3D network that underlies the structural and functional connectivity across the mammalian brain. Unravelling this complexity is a major challenge. Very little is known about the diversity and distribution of synapse types on individual neurons, the basic cellular building block of this network. The scope of the EU-funded SYNAPTOME project is to dissect the architecture of synapses in different types of neurons and determine their contribution to neuronal properties and functional output. Uncovering these fundamental principles of brain synaptic architecture will have important implications for neuroscience and neurological disorders.

Objective

Synapses participate in all our thoughts and actions and are damaged in over 100 genetic brain disorders. Synapses are the hallmark of brain complexity, being present in vast numbers and containing thousands of different proteins. Unravelling this complexity to get at the functional logic embedded within is a major challenge in neuroscience. We recently characterised excitatory synapse molecular diversity across the whole mammalian brain, revealing a remarkable 3D organisation of synapse types across the different regions – the ‘synaptome architecture’. This architecture is reorganised in genetic diseases, is important in structural and functional connectivity across the brain, and provides a mechanism for the storage and recall of information. But what of the fundamental, functional cellular building block of this architecture – the single neuron and its dendritic tree? Crucially, very little is known about the distribution of synapse types on individual neurons and what this actually means for brain function. The overarching goal of SYNAPTOME is to define single-neuron synaptome architecture (SNSA). We will develop new genetic labelling and computational approaches to systematically map SNSA in the mouse brain. We will identify the SNSA of specific functional types of neurons and determine whether neurons share a canonical SNSA. We will reveal how the SNSA is built during development and how it is relevant to the connections between neurons and their physiological properties and functional output. We will ask if the SNSA can direct us to the specific synapses damaged in genetic disorders. These studies will uncover fundamental design principles inherent in the building blocks of the brain that link genome, proteome and synaptome with the architecture and function of individual neurons and their organisation into brain-wide networks. The new tools, resources and knowledge that SYNAPTOME will bring will have wide application in neuroscience and disease research.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2019-ADG

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Host institution

THE UNIVERSITY OF EDINBURGH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 738 561,00
Address
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
United Kingdom

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Region
Scotland Eastern Scotland Edinburgh
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 738 561,00

Beneficiaries (1)

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