A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe <i>Pet1</i> neurons.

Abstract

Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of <i>Pet1</i>-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing <i>Pet1</i> neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-<i>Pet1</i> neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that <i>P2ry1-Pet1</i> DR neurons - the most molecularly distinct subtype - possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of <i>Pet1</i> neuron subtypes.