High-throughput mapping of single-neuron projection and molecular features by retrograde barcoded labeling

• DOI: 10.7554/elife.85419
• Publication Date: 2024-02-23T12:40:05Z
• Authors: Peibo Xu; Jian Peng; Tingli Yuan; Zhaoqin Chen; Hui He; Ziyan Wu; Ting Li; Xiaodong Li; Luyue Wang; Le Gao; Jun Yan; Wu Wei; Chengyu T Li; Zhen-Ge Luo; Yuejun Chen
• Keywords: Connectomics; Tracing

Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron patterns, but with limited throughput. Barcode-based connectomics maps large numbers single-neuron projections, remains challenge for jointly analyzing single-cell transcriptomics. Here, we established rAAV2-retro barcode-based multiplexed method that simultaneously characterizes projectome and transcriptome at single neuron level. We uncovered dedicated collateral projection ventromedial prefrontal cortex (vmPFC) to five downstream targets found projection-defined vmPFC are molecularly heterogeneous. identified transcriptional signatures projection-specific neurons, verified Pou3f1 as marker gene enriched projecting lateral hypothalamus, denoting distinct subset projections both dorsomedial striatum hypothalamus. In summary, have developed new technique whose paired connectome expression data can help reveal organizational principles form neural circuits process information.