RT Journal Article
SR Electronic
T1 Single-cell molecular connectomics of intracortically-projecting neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 378760
DO 10.1101/378760
A1 Esther Klingler
A1 Julien Prados
A1 Justus M Kebschull
A1 Alexandre Dayer
A1 Anthony M Zador
A1 Denis Jabaudon
YR 2018
UL http://biorxiv.org/content/early/2018/07/27/378760.abstract
AB The neocortex is organized into distinct areas, whose interconnectivity underlies sensorimotor transformations and integration1–7. These behaviorally critical functions are mediated by intracortically-projecting neurons (ICPN), which are a heterogeneous population of cells sending axonal branches to distinct cortical areas as well as to subcortical targets8–10. Although population-based11–14 and single-cell15–19 intracortical wiring diagrams are being identified, the transcriptional signatures corresponding to single-cell axonal projections of ICPN to multiple sites remain unknown. To address this question, we developed a high-throughput approach, “ConnectID”, to link connectome and transcriptome in single neurons. ConnectID combines MAPseq projection mapping17,20 (to identify single-neuron multiplex projections) with single-cell RNA sequencing (to identify corresponding gene expression). Using primary somatosensory cortex (S1) ICPN as proof-of-principle neurons, we identify three cardinal targets: (1) the primary motor cortex (M1), (2) the secondary somatosensory cortex (S2) and (3) subcortical targets (Sub). Using ConnectID, we identify transcriptional modules whose combined activities reflect multiplex projections to these cardinal targets. Based on these findings, we propose that the combinatorial activity of connectivity-defined transcriptional modules serves as a generic molecular mechanism to create diverse axonal projection patterns within and across neuronal cell types.