Abstract
An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input–output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.
Highlights
High-throughput single-cell RNA-sequencing efforts are creating transcriptomic cell-type censuses for multiple brain regions[7]
MOp-ul shares its lateral border with the primary somatosensory area (SSp); seen in Nissl- and NeuroTrace-stained sections as a transition from larger layer 5 (L5) somas in MOp to smaller somas in the SSp cell-sparse L5a and cell-dense L5b sublayers (Fig. 1b, Extended Data Figs. 2a, b; see the Allen Reference Atlas[33] (ARA) and http://brainmaps.org)
MOp is classically described as agranular cortex, but we identified a ‘granular’ L4, with densely packed small somas throughout primary (MOp) and secondary (MOs) motor cortex, albeit narrower than in SSp (Fig. 1b, Extended Data Fig. 2b; see algorithmic analysis of MOp–SSp border, revealing individual variations between animals in Extended Data Fig. 2c, d, Supplementary Information)
Summary
We established an integrated cross-laboratory anatomical analysis platform comprising myriad technologies, tools, methods, data analyses, visualizations and web-based portals for open access to data and tools[3,4,8,10,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27] (Extended Data Fig. 1, Methods). Our data suggest that the sets of regions providing input to Cre- and target-defined MOp-ul neuron types are similar, a surprising result given distinct axonal lamination patterns from cortical and thalamic sources[17,45] (Extended Data Fig. 16b). This result is consistent with other recent findings that global input patterns mapped with rabies tracer methods are independent of starter cell type[46]. MY-l-ipsi MY-m-ipsi MY-l-contra MY-m-contra Sp-cervical Sp-thoracic Sp-lumbar Sp-sacral log(barcode count) Depth (μm)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
