Multimodal Investigation of Functional and Structural Properties of the Human and Murine Hippocampus

The hippocampus is a medial temporal lobe structure critically involved in memory, spatial navigation, and emotional regulation, and is implicated in several neurological disorders. Despite its importance, a comprehensive understanding of its cytoarchitecture and neuronal organization in human and at the mesoscale level remains incomplete. The aim of this thesis is to generate high-resolution morpho-anatomical and functional datasets to support the development of single-cell–resolution computational models of human hippocampal subregions. To this end, a multimodal experimental workflow combining in vivo calcium imaging and ex vivo optical imaging techniques was developed and validated in mouse models and afterwards applied to human tissue. In vivo calcium imaging was used to characterize neuronal activity in the dorsal CA1 region, while ex vivo approaches, including immunofluorescence labeling, tissue clearing, light-sheet fluorescence microscopy, and two-photon microscopy, enabled high- resolution mapping of neuronal distribution and morphology. Overall, this work establishes an integrated pipeline for linking functional and structural data across multiple spatial scales, providing a framework for data-driven computational modeling of hippocampal organization with translational relevance to human brain tissue.