SpiLearn · Characterization of spinal learning in a repetitive yet skilled locomotor task
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2022-06-01 → 2024-05-31
- EU contribution
- €175,920
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Characterization of spinal learning in a repetitive yet skilled locomotor task
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.
Data: CORDIS, © European Union
Project objective
Animals adjust movement throughout their life to adapt to a changing environment and to learn new motor skills. The underlying mechanisms have been studied for decades, almost exclusively as a function of the brain. Interestingly, however, the spinal cord adapts and learns motor sequences without the brain, using only spinal sensory feedback. Therefore, the spinal cord must contain adequate neuronal circuitry for motor learning. This project aims to characterize brain-independent mechanisms of learning that take place within the spinal cord. With a complete thoracic transection, I will functionally isolate the lumbar spinal cord from the brain and enable hindlimb locomotion on a motorized treadmill with pharmacological stimulation. Using a skilled yet repetitive locomotor paradigm, I will identify cell-types indispensable for obstacle learning through circuit manipulation. Our preliminary data indicate that mice learn to avoid obstacles and improve their performance over weeks. We will test the integrity of this performance upon specific and acute inhibition of a selected neuronal population during the behavioral task. Furthermore, using in-vivo awake eletrophysiological recordings, I will characterize circuit dynamics that underlie motor learning capacity attributed to the spinal cord while mice perform the obstacle task. This project maximizes the synergies of the host lab’s expertise, i.e., kinematic analysis, circuit dissection, and the use of high-density Neuropixel probes, and my expertise in electrophysiological recordings in mouse spinal cord. In addition to implementing an innovative system of multichannel recordings of spinal circuits in behaving mice, knowledge gained from this project will enable linking cell-type specific activity profiles in the spinal cord to a motor learning behaviour for the first time. This link is an essential yet currently missing piece to understand how the spinal cord contributes to the acquisition of a new motor repertoire.
Original text from CORDIS.
Participants
- VIB VZW · ZWIJNAARDE - GENTCoordinatorBelgium
Links
Data: CORDIS, © European Union