Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. Here, we report photoactivated intersectional physiology sequencing (PIPseq), a technique for tagging and expression-profiling cells based on their functional properties. We demonstrate that PIPseq is capable of selecting rare cell types and enriching them by nearly one hundred-fold. We applied

more »

... PIPseq to the challenge of mapping receptor-ligand pairings among vomeronasal pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PIPseq identified the complete combinatorial receptor code for a specific set of ligands, and revealed that the primary sequence of a chemoreceptor was an unexpectedly strong predictor of functional similarity. Molecular markers have been a powerful tool for labeling and analyzing neuronal cell types. However, in many cases a single marker is insufficient to define a unique cell type, and may la-1 certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.