Journal
JOURNAL OF NEUROSCIENCE
Volume 42, Issue 41, Pages 7733-7743Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1062-22.2022
Keywords
axon branching; barcode; corticobulbar; corticospinal; motor cortex; pyramidal tract
Categories
Funding
- National Institutes of Health-National Institute of Neurological Disorders and Stroke [R34NS116713, R01NS061963]
- National Institutes of Health-National Cancer Institute [NCI P30-CA060553]
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This study used MAPseq to investigate the diversity of brainstem branching patterns of the pyramidal tract projections from the forelimb-related areas of the motor cortex. The results showed high yet systematic diversity in PT axons at the level of brainstem projection patterns. The projections from M1 and M2 were qualitatively similar, but with quantitative differences in subclasses and clusters.
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, M2CBULB) 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.
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