FunCoSpeedSpine · Mapping the functional connectome for speed control in spinal motor circuits
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-02-01 → 2020-01-31
- EU contribution
- €173,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Mapping the functional connectome for speed control in spinal motor circuits
Locomotion, be it by land, air or sea enables all creatures to navigate their environment. Animals move at a diverse speed to search for mates, catch prey and escape predation. A key aspect of this fundamental behavioural repertoire is the selection of an appropriate gait and speed that would guarantee the successful completion of the task at hand. While the decision to perform an action is initiated in the brain, the precise timing of motor neuron recruitment relies on neuronal networks in the spinal cord. Within the spinal cord, descending inputs are first parsed by assemblies of premotor interneurons, which convey correct patterns of excitation to pools of motor neurons innervating axial and limb muscles. An evolutionarily conserved source of ipsilateral excitatory premotor drive arises from cells called V2a neurons. These cells express the ChX10 transcription factor and have been described in terrestrial and aquatic vertebrates. V2a neurons are found both in the hindbrain and along the entire span of the spinal cord where they make direct connections with motor neurons and modulate the speed of locomotor actions. In this project, we aimed to use a combination of in vivo electrophysiology recordings, functional calcium imaging of network activity together with state of the art 3D sculped optogenetic stimulation restricted to single cells in vivo. Specifically, we wanted to tackle the following questions: 1. What are the synaptic connections among V2as and between V2a and MNs within the slow and fast range? 2. What is the degree of convergence and divergence between V2a neurons and MNs? 3. Finally, do supraspinal inputs to the spinal cord segregate based on speed? Performing this work would give us access to an unprecedented level of detail of how locomotor speed modules function in vivo, and would lead to a better understanding of the basic biological networks that allow adaptive locomotor flexibility.
Data: CORDIS, © European Union
Project objective
The study of spinal circuits underlying locomotion has a rich history, spanning over 100 years of research. Great efforts have been made to map out the connection patterns between motor neurons and different muscle targets. Yet, we know little about how premotor networks govern the recruitment of motor neurons and the control of speed. Recent advances in optogenetics, 3D light patterning and fluorescent-targeted patch clamp recordings of identified neurons now enable to map the functional connectome for speed control in spinal motor circuits. Here we will focus on the role of V2a excitatory premotor interneurons since these cells have the potential to act as a key nexus in the spinal network: i) spanning both in the hindbrain and spinal cord, ii) making direct connections with motor neurons and iii) modulating locomotor speed. Recent studies revealed piecemeal information related to the V2a to motor neurons connection pattern. By taking advantage of the optical clarity of the zebrafish larva, we will implement a comprehensive approach combining in vivo electrophysiology, state-of-the-art 3D optical stimulation of genetically targeted cells and functional calcium imaging to resolve the connectivity map of V2a neurons and answer 3 new key questions:1. What are the synaptic connections among V2as and between V2a and motor neurons within both slow and fast locomotion?2. What is the degree of convergence and divergence between V2a neurons and motor neurons? 3. Do supraspinal inputs to the spinal cord segregate based on speed?A talented young scientist, with a great track record and the right expertise to tackle these ambitious questions, will carry out the project in the prolific research environment offered by the Wyart lab at the Brain and Spine Institute in Paris. This effort will lead to high impact publications as well as to develop the necessary skills to launch an independent research career for the applicant.
Original text from CORDIS.
Participants
- INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union