How is information processed in the brain? How does the wiring of brain cells relate to their function? How does one brain differ from another?These are some of the most fundamental questions of neuroscience - and to answer them we need to study the functional activity of neurons in the brain in combination with their structure: their morphologies and crucially how they are connected with each other. In this LTP we will answer these questions in the mammalian brain, where we will link the physiology of a circuit in vivo with its detailed anatomy revealed by X-ray Holographic Nanotomography (XNH) and subsequent targeted volume electron microscopy (vEM) across landscapes extending beyond the >mm3 volumes required to fully contain the circuits. To this end, we will develop XNH for >mm3 volumes, new sample preparation, staining, and embedding methods for coherent X-ray imaging, and correlative pipelines to link all modalities.

How is information processed in the brain? How does the wiring of brain cells relate to their function? How does one brain differ from another? These are some of the most fundamental questions of neuroscience - and to answer them we need to study the functional activity of neurons in the brain in combination with their structure: their morphologies and crucially how they are connected with each other. In this LTP we will answer these questions in the mammalian brain, where we will link the physiology of a circuit in vivo with its detailed anatomy revealed by X-ray Holographic Nanotomography (XNH) and subsequent targeted volume electron microscopy (vEM) across landscapes extending beyond the >mm3 volumes required to fully contain the circuits. To this end, we will develop XNH for >mm3 volumes, new sample preparation, staining, and embedding methods for coherent X-ray imaging, and correlative pipelines to link all modalities.