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Redesigning brain circuits in development

Project description

Artificially redesigning the neural circuit in the brain

Optogenetics – the technique that uses light to activate neurons genetically modified to express light-sensitive ion channels – has revolutionised brain investigation. Although we are starting to understand how different parts of the brain control behaviour, how neural circuits assemble during development remains unknown. The EU-funded BrainRedesign project aims to genetically redesign specific circuits in an animal model and test the impact on innate and learned behaviour. Scientists will focus on the amygdala, a structure known for its role in processing rewarding stimuli and orchestrating behavioural responses. The investigation of this artificial circuit will unveil important insight into brain connectivity and plasticity.

Objective

In the pre-optogenetics era, molecular genetics defined the concepts of neural circuit development providing mechanistic insights into axon guidance and synapse assembly. However, this approach often revealed limited insights into the function of the circuits studied. Since 2005, optogenetics has revolutionized our approach to functionally dissect brain circuits and has tremendously increased our understanding of how they contribute to specific behaviours. However, how these circuits assemble during development remains mostly unknown. Here, I propose to combine these two approaches: to genetically redesign specific circuits during mouse development in a predictable fashion, and to test the consequences for innate and learned behaviour. This novel line of research follows concepts of synthetic biology, which aims at reconstructing cellular systems, with the intention of redesigning brain circuits to reroute information processing for new behavioural purposes. We aim to demonstrate that targeted mis-expression of connectivity signals can alter specific neural circuits and communications between circuit components along measurable hypotheses. Activation of such an artificial circuit, by either natural stimuli or optogenetics, is likely to produce a set of behavioural outcomes that will reveal general connectivity rules, the capacity for behavioural plasticity, and possible functional redundancies between circuits. Anatomical and physiological dissection of the redesigned circuit will reveal to what extent the incoming afferents instruct the target cells to produce their output responses. Our focus will be on the amygdala, a forebrain structure necessary for processing aversive and rewarding stimuli and orchestrating behavioural responses, and a brain circuit characterized by a high degree of cellular heterogeneity and interconnectivity. Overall, this work will provide important insights into the principles of developmental circuit wiring in the mammalian brain.

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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

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2019-ADG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
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.

€ 2 493 750,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
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.

€ 2 493 750,00

Beneficiaries (1)

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