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Large-scale subcellular ensemble dynamics in the mouse brain revealed by adaptive optics two-photon mesoscopy

Project description

Research into fine cellular structures could enhance understanding of higher brain functions

Higher brain functions like decision-making involve coordinated activity across multiple brain regions, including neuronal and non-neuronal cells. Recent advances in two-photon (2P) mesoscopy enable high-resolution monitoring of this activity but are limited by optical aberrations at increased imaging depths. To overcome this, the AdaM project will develop and validate the first adaptive optics mesoscope, combining adaptive aberration correction with large field-of-view 2P mesoscopy. Funded by the Marie Skłodowska-Curie Actions programme, researchers will benchmark this approach by imaging Ca2+ dynamics in small brain structures in living mice at great imaging depths. Then, they will record Ca2+ signals from astrocytes during decision-making tasks. Using information theory and machine learning, the team will extract emergent properties of cellular ensembles and their behaviour correlations.

Objective

Higher brain functions, such as decision-making, are associated with the coordinated activity of multiple cellular structures (e.g. cell bodies and cellular processes of neuronal and non neuronal cells) distributed over multiple brain areas. Recent technical developments enable monitoring this ensemble activity across different brain regions with high (i.e. cellular and subcellular) resolution using large field-of-view (FOV) two-photon (2P) mesoscopy. However, optical aberrations mostly due to light scattering strongly limit the application of these technologies when the imaging depth within the brain increases. To address this limitation, I will here design, develop, and validate the first adaptive optics (AO) mesoscope, combining the strength of adaptive aberration correction with the power of large FOV 2P mesoscopy. I will first benchmark this novel approach to image ensemble Ca2+ dynamics of small brain structures (e.g. processes of neuronal and non-neuronal cells) in living mice over large FOV and at increasing imaging depths. I will then focus on recording Ca2+ signals from processes of astrocytes, the main non-neuronal cell type in the brain, which play fundamental roles in brain physiology. I will study how networks of thin astrocytic structures encode behavioural information over multiple cortical regions during a decision- making task. Finally, I will apply analytical methods based on information theory and machine learning to extract emergent properties of distributed ensembles and their correlation with behaviour. In conclusion, I will combine expertise in optical engineering, neuroscience, and computation to reveal the functional dynamics of the fine cellular structures across multiple cortical areas. This project will allow extracting details about ensemble dynamics that have long remained inaccessible, contributing to elucidate the contribution of coordinated activity of cellular and subcellular structures to higher brain function and behaviour.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA
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.

€ 172 750,08
Address
VIA MOREGO 30
16163 GENOVA
Italy

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Region
Nord-Ovest Liguria Genova
Activity type
Research Organisations
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Total cost

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