Characterization of spinal learning in a repetitive yet skilled locomotor task

Project Information

SpiLearn

Grant agreement ID: 101067670

DOI

10.3030/101067670

Project closed

EC signature date 4 May 2022

Start date 1 June 2022

End date 31 May 2024

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 175 920,00

Coordinated by

VIB VZW
Belgium

Periodic Reporting for period 1 - SpiLearn (Characterization of spinal learning in a repetitive yet skilled locomotor task)

Reporting period: 2022-06-01 to 2024-05-31

Summary of the context and overall objectives of the project

A plethora of behavioral evidence indicates that the spinal cord, when isolated from brain inputs by a complete lesion, can still learn to adapt a motor behavior upon training. This project aimed to explore the extent to which the spinal cord can learn to adapt motor skills without involving the brain, and to understand the neuronal mechanisms involved.

Our initial objective was to demonstrate whether and how mice with spinal cord injuries can learn to perform repetitive motor tasks and find out the optimal conditions such learning. We did this by tracking their movements in detail using a motion capture system while they performed that tasks in with different set conditions.

In order to understand how neuronal circuits in the spinal cord allows mice to learn to perform motor tasks without the brain, we aimed to identify which specific types of neurons are involved in this motor learning, and what are their activity during learning, and during execution of the learned task. To do this, we used a combination of genetic techniques and virus-based methods to silence specific neurons and see their role. Finally, we analyzed the electrical activity of all the spinal neurons, and more specifically the ones that we identified as essential to perform the task. Through this approach, we aimed to understand through which mechanisms they contribute to learning.

Our findings reveal that the spinal cord has a remarkable ability to learn how to perform specific motor tasks without the brain, and this through the specific interaction of a newly identified circuit for learning and retention. Such discovery could eventually lead to new avenues of treatments for people with severe spinal cord injuries which according to the World Health Organization, impact between 250,000 and 500,000 people globally each year.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

To answer our first objective to understand the extent to which the spinal cord can learn to adapt motor skills without involving the brain, we used mice with severed spinal cords, effectively isolating their spinal cords from brain inputs. We took advantage of our motion capture kinematic tracking setup to analyze the strategies employed by these mice to perform repetitive motor tasks and conditioning tasks.
Remarkably, we found that mice with transected spinal cords can learn specific motor sequences without brain involvement and even navigate obstacles based solely on frequency of occurrence information.
Additionally, through cell-specific manipulations of chosen sensory and motor neurons of the spinal cord, we evaluated which neuronal types was essential in the learning and/or in the retention of motor tasks. We successfully identified two inhibitory spinal populations which are crucial for brain-independent learning and memory retention during that task.
Finally we performed, for the first time in vivo spinal cord recordings in awake, behaving mice while simultaneously tracking the 3D kinematics of their hindlimb, which allowed us to uncover the mechanisms behind spinal learning of a conditioning task in distinct cell types.

Through this project, we developed novel methods for spinal cord studies, enabling spinal neuronal recordings during treadmill locomotion with a stabilized spinal cord. This innovative methodology significantly advances the study of spinal cord function, particularly in the context of spinal cord injury, by providing a powerful new tool to understand how neural circuits are altered by such conditions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The project tackled fundamental questions in basic neuroscience, specifically exploring motor learning in the spinal cord independently of brain inputs. The findings shed new light on spinal cord physiology, revealing its capacity to learn specific motor sequences without brain involvement and even to avoid obstacles using only frequency of occurrence information. Additionally, we developed innovative methods for spinal cord studies, including in vivo recordings in the spinal cords of awake, behaving mice. Our work not only uncovered previously unknown mechanisms that could significantly influence rehabilitation and spinal cord repair strategies, but also introduced novel recording techniques that we hope will inspire future research and pave the way for high-density channel recordings in freely moving animals.