Abstract
Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal tract (PT). To better understand the diversity of the brainstem branching patterns of these pyramidal tract projections, we used MAPseq, a molecular barcode technique for population-scale sampling with single-axon resolution. In experiments using mice of both sexes, we first confirmed prior results demonstrating the basic efficacy of axonal barcode identification of primary motor cortex (M1) PT-type axons, including corticobulbar (CBULB) and corticospinal (CSPI) subclasses. We then used multiplexed MAPseq to analyze projections from M1 and M2 (caudal and rostral forelimb areas). The four basic axon subclasses comprising these projections (M1-CSPI, M1-CBULB, M2-CSPI, M2-CBULB) showed a complex mix of differences and similarities in their brainstem projection profiles. This included relatively abundant branching by all classes in the dorsal midbrain, by M2 subclasses in the pons, and by CSPI subclasses in the dorsal medulla. Cluster analysis showed graded distributions of the basic subclasses within the PT class. Clusters were of diversely mixed subclass composition and showed distinct rostrocaudal and/or dorsomedial projection biases. Exemplifying these patterns was a subcluster likely enriched in corticocuneate branches. Overall, the results indicate high yet systematic PT axon diversity at the level of brainstem branching patterns; projections of M1 and M2 appear qualitatively similar, yet with quantitative differences in subclasses and clusters.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7733-7743 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 42 |
| Issue number | 41 |
| DOIs | |
| State | Published - Oct 12 2022 |
Funding
Received June 1, 2022; revised Aug. 22, 2022; accepted Aug. 25, 2022. Author contributions: G.M.G.S. designed research; F.S.H., M.E.M., H.Z., and G.M.G.S. performed research; F.S.H., J.M.B., H.Z., and G.M.G.S. analyzed data; and G.M.G.S. wrote the paper. This work was supported by National Institutes of Health–National Institute of Neurological Disorders and Stroke Grants R34NS116713 and R01NS061963 to G.M.G.S. and National Institutes of Health–National Cancer Institute Grant NCI P30-CA060553 to Robert H. Lurie Comprehensive Cancer Center of Northwestern University. We thank Kamil Wojdyla and Katherine Gruner of the Northwestern University Mouse Histology and Phenotyping Laboratory for advice and assistance with cryosectioning, the MAPseq Core facility at Cold Spring Harbor Laboratory, and Tony Zador for advice throughout the project. *F.S.H. and J.M.B. contributed equally to this work. The authors declare no competing financial interests. Correspondence should be addressed to Gordon M. G. Shepherd at [email protected]. https://doi.org/10.1523/JNEUROSCI.1062-22.2022 Copyright © 2022 the authors
Keywords
- axon branching
- barcode
- corticobulbar
- corticospinal
- motor cortex
- pyramidal tract
ASJC Scopus subject areas
- General Neuroscience