# The Primate Corticospinal Connectome and Transcriptome

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $630,880

## Abstract

Project Summary
Efforts to promote recovery of function after human spinal cord injury (SCI) will likely require interventions
targeting the corticospinal motor system, the most important pathway for voluntary motor control in
humans. In a series of studies over the past 4 years we have found that corticospinal tract (CST) axons
regenerate into spinal cord neural stem cell (NSC) grafts placed into sites of SCI in mice, rats and
monkeys. These regenerating CST axons form synapses with the graft, and the graft in turn extends very
large numbers of new axons from the injury site over long distances into the distal spinal cord. Neural
relays across the injury are thereby formed, supporting functional improvement. This work is on a human
translational path and IND-enabling work is in progress.
This grant proposes two new directions that will be critically important in supporting human translation.
First, we recently reported that injured adult mouse CST neurons revert to an embryonic transcriptional
state that lasts for two weeks after SCI, a time during which CST axons can regenerate. This finding
establishes a critical period for intervention after mouse SCI to support recovery. Does the same
transcriptional reversion to a pro-growth embryonic state occur in the primate brain? If so, how long does
it last? Work in Aim 1 will definitively answer this question, identifying for the first time what may be an
optimal time window for therapeutic intervention of any type to support functional recovery in primates,
including humans. We will perform RNA sequencing (RNAseq) specifically of CST neurons after SCI in
rhesus monkeys using intersectional viral approaches, based on supportive preliminary data in monkeys.
In Aim 2 we propose for the first time using novel viral vectors to anterogradely, trans-synaptically trace
primate corticospinal projections to the spinal cord. Our preliminary studies demonstrate that rodent CST
axons project nearly entirely to spinal cord interneurons, whereas in primates the vast preponderance of
CST axons terminate directly on alpha motor neurons. Knowing the precise targets of CST projections to
the spinal cord will both markedly extend our basic knowledge of motor system organization in primates,
and will allow optimization of stem cell graft properties to enhance neural relay formation across sites of
SCI. Unlike other neural stem cell programs for SCI, our work aims to directly re-form critical neural
relays across a severe injury, rather than target spared axons through grafts of OPCs; knowledge gained
from this aim could markedly improve relay formation across injury sites in the primate system.

## Key facts

- **NIH application ID:** 10650134
- **Project number:** 5R01NS104442-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MARK H. TUSZYNSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $630,880
- **Award type:** 5
- **Project period:** 2017-09-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10650134

## Citation

> US National Institutes of Health, RePORTER application 10650134, The Primate Corticospinal Connectome and Transcriptome (5R01NS104442-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10650134. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*