In order to reveal principles of neural circuit operation, it would be useful to simultaneously examine molecular profiles of neurons and structural connectivity between neurons, ideally through an animal’s entire nervous system.  C. elegans is a suitable model for such analysis, due to its small nervous system with known stereotypical connectivity.  However, a method for profiling transcriptomic expression at single-neuron resolution over the entire animal is currently lacking.  We recently developed Expansion of C. elegans (ExCel), a method to physically expand fixed entire animals of C. elegans by ~3.3-3.8x in each dimension with high isotropy.  ExCel enables simultaneous readout of fluorescent proteins, RNAs, DNA and morphological features at a resolution of ~70 nm.  We showed that ExCel can be used to perform gene expression analyses of multiple neurons inside the same animal.  While its current form can only image up to 3-5 mRNA targets, combination with other tools developed by the group, such as in situ nucleotide sequencing of expanded tissues, could potentially enable multiplexed readout of more than hundreds or thousands of targets.  In this talk, I will discuss several expansion-mediated RNA imaging methods, their tradeoffs, and progresses on adopting them on C. elegans.