# Brainstem circuits of corticospinal neurons

> **NIH NIH R34** · NORTHWESTERN UNIVERSITY · 2020 · $693,225

## Abstract

PROJECT SUMMARY
Corticospinal axonal projections are critical for mammalian motor control. Their length and complexity makes
them vulnerable to an exceptionally wide range of neurological disease processes including cerebrovascular
disorders, demyelinating diseases, ALS, spinal cord injury, and more. Corticospinal research has naturally
focused on cortical and spinal mechanisms. However, corticospinal axons, like those of other types of pyramidal
tract neurons, can send branches to the midbrain, pons, and medulla along the way to the spinal cord. The
anatomical “projectome” of corticospinal axonal branching to brainstem targets has not been systematically
investigated. Even less is known about the synaptic “connectome”; i.e., the cellular circuits formed by
corticospinal input to postsynaptic neurons in various brainstem nuclei. Elucidating the brainstem circuits of
corticospinal axons will be important for understanding the cellular basis of mammalian motor control. For
example, there very likely are as-yet unrecognized subtypes of corticospinal neurons that, through differential
innervation of brainstem targets, mediate specific sensorimotor, neuromodulatory, or other functions essential
for motor coordination and control. We propose a two-pronged approach to investigate the brainstem branches
and circuits of corticospinal axons in the mouse. In Aim 1, we will use a high-throughput molecular barcoding
technique, MAPseq, to characterize the diversity and complexity of corticospinal projections to the brainstem,
with single-axon resolution and large-scale sampling. In Aim 2, we will use optogenetic, electrophysiological,
imaging, and viral labeling tools to characterize the cell-type-specific synaptic connectivity in these circuits. The
projections and connections of corticospinal axons’ brainstem branches will be both broadly surveyed across
regions (midbrain, pons, medulla) and analyzed in a more focused manner at the level of specific types of
projection neurons in key nuclei, including those associated with sensorimotor, neuromodulatory, and other
systems (reticular, pontine, cuneate, locus coeruleus, and more). Results from this discovery-oriented research
program will lay the groundwork for future hypothesis-oriented studies to investigate – at the mechanistically
important level of specific cell types and their synaptic connectivity – how the brainstem circuits of corticospinal
neurons contribute to mammalian motor function.

## Key facts

- **NIH application ID:** 9977340
- **Project number:** 1R34NS116713-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Gordon M Shepherd
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $693,225
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977340

## Citation

> US National Institutes of Health, RePORTER application 9977340, Brainstem circuits of corticospinal neurons (1R34NS116713-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977340. Licensed CC0.

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