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Multiphoton Voltage Imaging

Understanding the brain is one of the great scientific challenges of our time. This pursuit fundamentally depends on advances in physical sciences and engineering to provide novel tools and methods to perturb, record and interpret... see more

31/03/2025

TU Delft

1M€

Project Budget: 1M€

Project leader

TECHNISCHE UNIVERSITEIT DELFT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2025-03-31

ERC-2019-STG: ERC Starting Grant Scope:Objectives

I+D

Cerrada does 6 years

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characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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2 Participantes

TU Delft

1.50M€ | Leader

ANDIA LACTEOS DE CANTABRIA

850.45K€ | participant

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Project duration: 64 months Date Start: 2019-11-18
End date: 2025-03-31

Project leader

TECHNISCHE UNIVERSITEIT DELFT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 1M€

participation deadline Sin fecha límite de participación.

Project description Understanding the brain is one of the great scientific challenges of our time. This pursuit fundamentally depends on advances in physical sciences and engineering to provide novel tools and methods to perturb, record and interpret brain activity. Information in the brain is encoded in changes in the voltage across the membrane of brain cells. Voltage imaging with genetically encoded voltage indicators (GEVIs) is a revolutionary method that allows faithful recording of the fast electrical dynamics of many genetically targeted cells in parallel. This provides an unprecedented means to record how patterns of change in this membrane voltage, called action potentials, manifest in subcellular compartments, cells, and networks across the brain, which is the only way to arrive at a fundamental understanding of brain functions like learning and memory, and of neurogenerative diseases. For this promise to be fulfilled, we need voltage imaging deep in the living brain of awake and behaving organisms. To achieve this, I will evolve a GEVI optimized for three-photon (3P) imaging, by screening mutant libraries of GEVIs directly for brightness and photostability under 3P-excitation, voltage sensitivity, and membrane trafficking in neurons. I will optimize the photocycle dynamics of GEVIs with temporally structured light, using a NOPA with tunable repetition rate, pockels cell and multiple optical delay lines, to create optimal 3P excitation protocols. Crucially, this optimization will not depend on spectral phase and is therefore compatible with high speed multiphoton imaging, aberration correction, and deep tissue imaging. Finally, I will investigate memory formation in a proof-of-principle experiment. I will use a custom microscope I developed, for 3P voltage imaging of cells in the cerebellum of mice trained in an eyeblink task. Memory formation in this paradigm is hypothesized to look like subtle changes in the exact shape and timing of action potentials, which I will resolve.

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