Correlative X-ray holographic nanotomography and spatial transcriptomics in the mouse brain olfactory bulb

The detection and discrimination of odours is efficiently performed by the olfactory system of most living species, yet a mechanistic understanding is not clear: the ‘olfactory code’, linking chemical identity to activated neurons - is lacking. Here we aim to reveal this code by studying a ~0.3mm^3 volume of tissue of the mouse olfactory bulb. We will for the first time correlate the spatial transcriptome of a soft tissue with its sub-500nm detailed structure brought by X-ray holographic nanotomography on fixed, frozen, unstained brain tissue. This experiment will reveal the identity of neighbouring glomerular columns, their gain and the molecular diversity of projection neurons that sample the same glomerulus. Altogether, our study will establish the first protocol to reveal subcellular structure and molecular insights on the same neuronal circuit, and pave the way for future research in systems neuroscience as well as in broader soft tissue research.