# Strategies to maximize the functional benefit of regenerated corticospinal tract axons

> **NIH NIH R01** · MARQUETTE UNIVERSITY · 2020 · $330,313

## Abstract

PROJECT SUMMARY
 A major effort in regenerative neuroscience is to improve axon growth after injury to the central nervous
system (CNS). Once growth is achieved, however, a second hurdle to improving function is that regenerated
axons must succeed in forming synaptic contacts with appropriate sets of post-synaptic neurons. The challenge
of restoring effective circuitry is especially acute after spinal injuries that damage the corticospinal tract (CST), a
pathway critical for fine motor control. The CST mediates descending motor control by synapsing on specific
subsets of spinal neurons, which in humans and rodents alike include a diverse set of interneurons in addition
to the direct CST-motor-neuron contacts that characterize primates. The field has achieved increasing success
in promoting CST axon growth, yet gains in behavioral recovery have lagged. This work will address the need
to monitor the connectivity of regenerated CST axons, and to optimize their behavioral output. To do so we will
employ rodent models of spinal injury and capitalize on combined stem cell bridging and viral expression of a
pro-regenerative gene called KLF6, which we recently found to evoke robust regenerative CST growth. In
addition, we will leverage a recently developed trans-synaptic viral labeling technique that enables an
unprecedented ability to visualize post-synaptic target selection. First, we will render KLF6 expression
controllable and reversible, in order to silence KLF6 after regeneration occurs in order to determine whether
prolonged KLF6 expression itself interferes with behavioral recovery. This will address the pressing question of
the degree to which pro-regenerative growth mechanisms may come at the expense of effective synaptic
refinement or target selection. Next, we will test the ability of rehabilitative training to sculpt target selection by
regenerating CSTs and improve their behavioral output. Finally, we will employ both electrical and chemogenetic
means to chronically elevate activity in regenerating CST axons, which we hypothesize will both enhance CST
sprouting and improve competition for synaptic territory. These complementary approaches will create optimal
strategies to maximize the behavioral benefit that can be extracted from regenerated CST axons.

## Key facts

- **NIH application ID:** 9948773
- **Project number:** 5R01NS107807-03
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Murray G Blackmore
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,313
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948773

## Citation

> US National Institutes of Health, RePORTER application 9948773, Strategies to maximize the functional benefit of regenerated corticospinal tract axons (5R01NS107807-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948773. Licensed CC0.

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