Bright, coherent and focused light to resolve neural circuits

ongoing

The overarching goal of this project is to establish a novel technique for neuroimaging to probe large tissue volumes at the nanometre scale. Currently only electron microscopes are capable of generating data with sufficient resolving power for comprehensive exploration of the neural circuits that underlie brain function. With state of the art systems, imaging just one cubic mm of brain entails years of data collection, ultra-thin sectioning which is prone to errors and data loss, and prohibitive costs. Each circuit unit spans over large distances, thus access to millimetre sized volumes of view is essential for both fundamental and therapeutic discoveries in neurosciences. Today this is an unreachable goal. In contrast, X-ray microscopy facilitates rapid imaging of large samples but the resolving power is not sufficient to visualize neural connections. Thus, at present, resolving large neural circuits is hardly imaginable. The aim of this project is to overcome these limitations and to develop an integrative approach which will open new research perspectives. X-ray holographic nano-tomography is a 3D coherent imaging technique which is capable of generating exceptional contrast in soft tissue through phase contrast. The penetrating power of X-rays and the full-field, free space propagation setup enable rapid multiscale imaging of large samples which are opaque to visible light. By combining a highly brilliant X-ray nanoprobe, a carefully designed nanopositioning system, a cutting edge detection system and cryogenics for sample preservation, isotropic 3D spatial resolution better than 30 nm is conceivable. The objectives of this interdisciplinary project are to 1) develop a system for imaging neural circuits at synaptic level in large tissue volumes, including methods for sample preparation, image acquisition and image reconstruction 2) develop an automatic image analysis tool 3) create unprecedented maps of brain circuits with immediate impact in neurosciences.