Descripción del proyecto
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.