Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types

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Science  13 Dec 2019:
Vol. 366, Issue 6471, pp. 1384-1389
DOI: 10.1126/science.aax8055

Cell-type identification in neural circuits

In many cases, a single molecular marker is insufficient to define a specific cell type and may label a few, or a few hundred, physiologically distinguishable cell types. Lee et al. developed a high-throughput technique, called physiological optical tagging sequencing (PhOTseq), for identifying the expression profile of cells that exhibit a particular physiological profile (see the Perspective by Renninger). They used PhOTseq to identify genes encoding vomeronasal receptors in mice, which detect pheromones and subserve social communication.

Science, this issue p. 1384; see also p. 1311


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. We developed physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression profiling of cells on the basis of their functional properties. PhOTseq was capable of selecting rare cell types and enriching them by nearly 100-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands.

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