Empowering Neurological Recovery: Light-Sheet Microscopy and Targeted Interventions

Session

Poster Session

Authors

Laura Batti (1), Newton Cho (2), Jordan Squair (2), Ivana Gantar (1), Yoseline Cabara (1), Quentin Barraud (2), Grègoire Courtine (2), Stèphane Pages (1)

Affiliations

1. 6Wyss Center for Bio and Neuroengineering, Geneva, Switzerland
2. Defitech Center for Interventional Neurotherapies (.NeuroRestore), CHUV/UNIL/EPFL, Lausanne, Switzerland

Keywords

Lightsheet

Tissue clearing

Translational neuroscience

Abstract text

Lightsheet microscopy has emerged as a powerful technology in neuroscience, providing profound insights into the structure and organization of biological circuits within intact and cleared organs. In this study, we underscore the transformative potential of lightsheet microscopy and its related techniques in driving advances in both neuroscience and medicine.

 

At the Wyss Center for Bio and Neuroengineering in Geneva, Switzerland, we've established a sophisticated pipeline integrating cutting-edge, custom-tailored tools. This pipeline is designed to enable the imaging of whole organs with high temporal or spatial resolution. Our facility boasts a customized version of the COLM/SPED for near diffraction-limited resolution imaging of large, clarified samples (ranging in size up to cm), as well as a large-scale imaging system, mesoSPIM, tailored for screening a vast number of samples at cellular resolution.

 

Through our work, we demonstrate that this integrated pipeline not only provides valuable insights into the underlying mechanisms of spinal cord injury (SCI) recovery but also serves as a guide for targeted interventions. Leveraging a combination of viral tracing, transcription factor labelling, tissue clearing, lightsheet imaging, and atlasing, we've successfully constructed an unbiassed space-time brain-wide atlas. This atlas delineates transcriptionally active neurons and spinal cord projecting neurons crucial for the recovery of walking after incomplete SCI.

 

These groundbreaking discoveries, validated through optogenetic and behavioral tests in rodent models, were subsequently translated into clinical applications. Notably, deep brain stimulation targeted at the identified brain region facilitated functional recovery in two human participants with incomplete SCI.

 

This study exemplifies the promise of innovative techniques like lightsheet microscopy on whole organ in advancing our understanding of neurological disorders and facilitating the development of targeted therapies with real-world impact.

 

References

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