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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... 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. ver más
31/03/2025
TU Delft
1M€
Duración del proyecto: 64 meses Fecha Inicio: 2019-11-18
Fecha Fin: 2025-03-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2019-11-18
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG: ERC Starting Grant
Cerrada hace 6 años
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
TECHNISCHE UNIVERSITEIT DELFT No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5