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Assembly and plasticity of inhibitory cortical networks by early learning experience

Project description

Studying how early life experiences influence brain development

The extraordinary diversity of animal behaviours relies on the precise assembly and fine-tuning of synapses in the brain. This connectivity reaches an exceptional level of complexity in the mammalian cerebral cortex, where experience-dependent plasticity endows neural circuits with the flexibility required for adapting to a continuously changing environment. While learning occurs throughout an individual's lifetime, several studies have shown that learning during the early periods of postnatal development has a transformative effect on functional performance later in life. The goal of the EU-funded EXPERIENTIA project is to understand the mechanisms through which enhanced sensory experience during development sculpts cortical circuitries to improve behavioural performance in mice. The research will shed light on the mechanisms shaping the assembly and function of cortical circuitries during early sensory experience.

Objective

The extraordinary diversity of animal behaviors relies on the precise assembly and fine-tuning of synapses in neuronal circuits that adapt to an ever-changing environment. Hence, mature networks are the final expression of experiences accumulated throughout our life. Importantly, young brains are more amenable to learning that older brains, but the neural mechanisms underlying these differences remain largely unknown. In the cerebral cortex, for example, there are two main classes of neurons, excitatory projection neurons (pyramidal cells) and inhibitory neurons (interneurons). Interneurons have a remarkable capability to sense changes in sensory experience and therefore occupy a unique position to orchestrate circuit remodeling. The goal of this project is to understand the mechanisms through which enhanced sensory experience during development sculpts cortical circuitries to improve behavioral performance in mice. To this end, we will use: (1) a synaptic connectivity mapping strategy (e-GRASP) and an activity-dependent promoter to explore specific cell- and synaptic-specific reorganizations driven by sensory experience; (2) sensory discrimination tasks and two-photon microscopy to explore the emergence of cortical functional properties, cell ensembles and behavioral performance; (3) unbiased screenings in cell populations and specific synapses together with single-cell RNA sequencing to identify genes that regulate cell-type specific modifications; and (4) loss of function approaches (shRNA and CRISPR/Cas9) to analyze the role of the identified candidate genes. Our research will shed light on the mechanisms shaping the assembly and function of cortical circuitries during early sensory experience.

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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

KING'S COLLEGE LONDON
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.

€ 2 499 990,00
Address
STRAND
WC2R 2LS London
United Kingdom

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Region
London Inner London — West Westminster
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.

€ 2 499 990,00

Beneficiaries (1)

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