Multi-Scale Molecular Deconstruction of the Serotonin Neuron System

Benjamin W. Okaty, Morgan E. Freret, Benjamin D. Rood, Rachael D. Brust, Morgan L. Hennessy, Danielle deBairos, Jun Chul Kim, Melloni N. Cook, Susan M. Dymecki

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance.

Original languageEnglish (US)
Pages (from-to)774-791
Number of pages18
JournalNeuron
Volume88
Issue number4
DOIs
StatePublished - Nov 18 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Multi-Scale Molecular Deconstruction of the Serotonin Neuron System'. Together they form a unique fingerprint.

Cite this