Group leader: Julien Bouvier

Neuronal Circuits & Motor Control

In brief

Our research aims at identifying the neuronal circuits that execute movements and support their adaptive nature. We principally study breathing and locomotion, two vital behaviors that are largely conserved across species. Our current research projects aim at unveiling how breathing and locomotion are dynamically modulated according to internal or external needs, such as transition from rest to exercise, changes in posture or locomotor direction. These questions are addressed by a multidisciplinary strategy combining state-of-the-art viral-based anatomical tracings on dedicated transgenic mouse lines, neuro-anatomy, and functional investigations using electrophysiology, optogenetic and behavioral analysis.

To understand brain related diseases we need to understand the operation of the different neuronal networks that generate normal brain functions. This requires deciphering the identities and operating principles of cells executing of the function locally, as well as that of cells standing upstream its purposeful manifestation.
The team addresses this question on the motor behaviors of breathing and walking which are exquisite model systems with privileged experimental accessibility and strong translational outcomes. In these systems, tools from developmental biology are increasingly applied to manipulate – being to trace, record, kill, or modify the connectivity or activity of – subsets of neurons on the basis of their shared history of expression of specific developmental genes. This is progressively unlocking access to homogenous cell types embedded within complex architectures while informing on the intrinsic building logic of neural networks. In combination with functional investigations ex-vivo and behavior in vivo, this led rapid progress in identifying interneuronal subtypes with dedicated functions in the executive circuits for walking or breathing, often referred to as central pattern generators or CPGs. In contrast, the neuronal architecture that stand upstream the CPGs and condition their activity remains elusive. We are exploring this through two parallel projects that both touch upon the cooperative roles of clusters of brainstem and spinal cord neurons in elaborating adaptive respiratory and locomotor behaviors.

  • Anatomical and functional investigation of the neuronal substrate linking respiration and locomotion. Respiratory increase during exercise is probably the most striking example of respiratory adaptation. While a direct influence of the locomotor neuronal circuit onto the respiratory CPG has been proposed, it has remained largely uncharted. We are currently exploring the neuronal connections that originate in the locomotor circuit, being the CPG in the spinal cord and/or its upstream controllers in the brainstem, and that impinge onto the respiratory CPG and upregulate breathing during locomotor engagement.
  • Anatomical and functional investigation of reticulospinal neurons controlling locomotion. While the locomotor CPG contains all the elements necessary for producing the normal walking sequence, it is under obligatory control from descending signals conveyed by brainstem reticulospinal neurons. Yet the identities of reticulospinal neurons and that of their post-synaptic partners in the spinal CPG are still little resolved. We are currently addressing this with a particular focus on genetically-identified reticulospinal neurons that control limb movements.

Visit also our external website.

Selected publications

  • Usseglio G, Gatier E, Heuzé A, Hérent C, Bouvier J. Control of orienting movements and locomotion by projection-defined subsets of brainstem V2a neurons. Current Biology, 2020. https://doi.org/10.1016/j.cub.2020.09.014. Open-access full text.
  • Schwenkgrub J, Harrell ER, Bathellier B, Bouvier J. Deep imaging in the brainstem reveals functional heterogeneity in V2a neurons controlling locomotion. Science Advances, 2020 Dec 4;6(49):eabc6309. Open-access full text or download pdf.
  • Hérent C, Diem S, Fortin G, Bouvier J. Absent phasing of respiratory and locomotor rhythms in running mice. eLife, 2020. Dec 1;9:e61919. doi: 10.7554/eLife.61919. Full text on eLife or download pdf.
  • Skarlatou S, Hérent C, Toscano E, Mendes C, Bouvier J, Zampieri N. Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection. Cell Reports, 2020 Jun 9;31(10):107741. doi: 10.1016/j.celrep.2020.107741. Pubmed link. Open-access full text.
  • Bouvier J*#, Caggiano V*, Leiras R, Caldeira V, Bellardita C, Balueva K, Fuchs A, Kiehn O#. (*co-first and # co-corresponding). Descending Command Neurons in the Brainstem that Halt Locomotion. Cell. 2015 Nov 19;163(5):1191-1203. Full text available on Cell website.

2022



July: we organize and host the
1st pre-FENS Satellite symposium for ECRs on Neuronal Motor Circuits.

13 early career researchers from several laboratories worldwide including our own will cover the cell types and circuits for movement and sensory processing in the spinal cord, the organization of descending motor tracts, as well as integrated and adaptive motor control.

Registration is free, but mandatory here!

The symposium will be held within our walls, with support of the Institute.

 

 

 


March: the team receives the “Team FRM” label!

Guarantee of excellence, the “Team FRM” label is awarded by Fondation pour la Recherche Médicale for three years and aims to fund innovative work in biology, with a high potential for application in human health. In 2022, the FRM selected 50 projects including ours on reticulospinal neurons in locomotor control and recovery following spinal cord injury.

 

2021


December: Julien defends the HDR (Habilitation à Diriger des Recherches).

The HDR is a mandatory step for a PI to continue supervising PhD students. It is delivered by the University after a thesis evaluation and an oral defense. A bit like a second PhD!

 

 

July: new preprint for the lab on bioRxiv!
We just uploaded our recent findings on the linker circuits between respiratory and locomotor central networks. Brilliant work done by former PhD student Coralie Hérent!


July: 2 new projects funded by ANR in the team.

We are part of two funded projects by the french National Agency for Research, from the AAPG2021 and the CRCNS 2021 calls, dedicated to brainstem/spinal cord circuits in controlling locomotion and orientation in health and following spinal cord injury!

 


January: Coralie Hérent obtains her PhD.

Brilliant defense of her work titled: Respiratory adaptation to running exercise: a behavioural and neuronal circuits study in mice”. What an exciting day and enriching 4+ years of work in the lab !

 

2020



January: A new ANR grant starts for our lab!

The lab is part of an 3 partite collaboration to study the functional connectomics underlying postural control, funded by the National Agency for Research.

 

December 2020: the last paper of the year is out!!
DOI: 10.1126/sciadv.abc6309. Or download pdf here.
This work is from a great collaboration with Brice Bathellier’s lab. We pioneered pioneered the use of deep-brain maging with the Inscopix miniscope to image the activity of deep brainstem neurons in vivo during locomotion.

December 2020: first paper for PhD student Coralie Hérent!!
These results challenge the concept that breathing and locomotor rhythms are coupled in a relatively fixed manner during running, and introduce the mouse model as part of the toolbox to investigate how breathing is augmented during running exercise.

 

Oct. 2020: the very first published work of the lab, by PhD student Giovanni Usseglio is now online!
https://doi.org/10.1016/j.cub.2020.09.014. Get the full text here.
Using viral tracings, circuit optogenetics and chemogenetic silencing, we identify the reticulospinal neurons that command multiple motor actions linked to orientation and locomotion.

 

June 2020: the lab contributed important new findings!
Open-access full text.
The first paper with contribution from our PhD student Coralie Hérent is out!! Check out this exciting study examining the impact of axonal signaling during development on the left-right coordination of limb mouvements in mice. A fruitful collaboration with the group of Niccolò Zampieri, who led this research!

 

September 2020: PhD Student obtains a doctoral fellowship!
Edwin Gatier obtains the 3-year doctoral fellowship from our graduate school, ED568 BIOSIGNE. Welcome Edwin and let’s do great science!

 

PhD students, postdoctoral fellows and technical staff:

Undergraduate students:

  • Adrien Barralis, May-July 2022. Undergraduate (M1) student, BIP, Sorbonne University.
  • Manon Papadiamandis, April/May 2022. Undergraduate (L2) student, Chemistry & Life Sciences, University Paris-Saclay.
  • Aurélie Jouy, May/June 2021. Undergraduate (M1) student, University Paris-Saclay.
  • Alexis d’Humières, June/July 2021. Undergraduate (M1) student, Sorbonne University.
  • Clara Depond, June/July 2021. Undergraduate (L2) student, Sup’Biotech Paris.
  • Juliette Mondy, June/Juny 2019. Undergraduate (L2) student, Sup’Biotech Paris.
  • Manimega Vidjeacoumar, June 2018. Undergratuate (L2) student, UPMC Paris.

Publications of the team or with team members :

  • Usseglio G, Gatier E, Heuzé A, Hérent C, Bouvier J. Control of orienting movements and locomotion by projection-defined subsets of brainstem V2a neurons. Current Biology, 2020. https://doi.org/10.1016/j.cub.2020.09.014. Open-access full text.
  • Schwenkgrub J, Harrell ER, Bathellier B, Bouvier J. Deep imaging in the brainstem reveals functional heterogeneity in V2a neurons controlling locomotion. Science Advances, 2020 Dec 4;6(49):eabc6309. Open-access full text or download pdf.
  • Hérent C, Diem S, Fortin G, Bouvier J. Absent phasing of respiratory and locomotor rhythms in running mice. eLife, 2020. Dec 1;9:e61919. doi: 10.7554/eLife.61919. Full text on eLife or download pdf.
  • Skarlatou S, Hérent C, Toscano E, Mendes C, Bouvier J, Zampieri N. Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection. Cell Reports, 2020 Jun 9;31(10):107741. doi: 10.1016/j.celrep.2020.107741. Pubmed link. Open-access full text.

Previously published work of the team leader:

  • Caggiano V*, Leiras R*, Goñi-Erro H, Masini D, Bellardita C, Bouvier J, Caldeira V, Fisone G, Kiehn O (2017). Midbrain circuits that set locomotor speed and gait selection. Nature. doi:10.1038/nature25448. Full text available from PMC. Abstract on Nature Website.
  • Wu J, Capelli P, Bouvier J, Goulding M, Arber S, Fortin G (2017). A V0 core neuronal circuit for inspiration. Nat Commun. Sep 15;8(1):544. doi: 10.1038. Full text available.
  • Bellardita C, Caggiano V, Leiras R, Caldeira V, Fuchs A, Bouvier J, Löw P, Kiehn O. (2017) Spatiotemporal correlation of spinal network dynamics underlying spasms after spinal cord injury. eLife, Feb 13 ;6. Full text available from eLIFE or PMC.
  • Hernandez-Miranda LR, Ruffault PL, Bouvier J, Murray AJ, Morin-Surun MP, Zampieri N, Cholewa-Waclaw JB, Ey E, Brunet JF, Champagnat J, Fortin G, Birchmeier, C (2017). Genetic identification of a hindbrain nucleus essential for innate vocalization. Proc. Natl. Acad. Sci U.S.A. Jul 25 ;114(30):8095-8100. Full text available.
  • Bouvier J, Caggiano V, Leiras R, Caldeira V, Bellardita C, Balueva K, Fuchs A, Kiehn O (2015). Descending Command Neurons in the Brainstem that Halt Locomotion. Cell. 2015 Nov 19 ;163(5):1191-1203. doi : 10.1016/j.cell.2015.10.074. Full text available from PMC.
  • Bouvier J (2014). Neurons in motion : genetics reveal a dual organization of locomotor networks controlling left-right alternation. Médecine/Sciences, Feb ;30(2):121-4. Full text (french) available from Médecine/Sciences.
  • Talpalar AE*, Bouvier J*, Borgius L, Fortin G, Pierani A, Kiehn O (2013). Dual-mode operation of neuronal networks involved in left-right alternation. Nature Aug 1 ;500(7460):85-8. Pubmed
  • Thoby-Brisson M, Bouvier J, Glasco DM, Stewart ME, Dean C, Murdoch JN, Champagnat J, Fortin G, Chandrasekhar A (2012). Brainstem Respiratory oscillators develop independently of neuronal migration defects in the Wnt/PCP mouse mutant looptail. PLoS ONE, 7(2) : e31140. Full text.
  • Ramanantsoa N, Hirsch MR, Thoby-Brisson M, Dubreuil V, Bouvier J, Ruffault P-L, Matrot B, Fortin G, Brunet JF, Gallego J, Goridis G (2011). Breathing without CO2 Chemosensitivity in Conditional Phox2b Mutants. Journal of Neuroscience, Sep ; 31 (36) : 12880-12888. Full text.
  • Bouvier J, Thoby-Brisson M, Renier N, Dubreuil V, Ericson J, Champagnat J, Pierani A, Chédotal A, Fortin G (2010). Hindbrain Interneurons and Axon Guidance Signaling Critical for Breathing. Nature Neuroscience, Sep ;13(9):1066-74. Pubmed
  • Bouvier J, Autran S, Dehorter N, Katz DM, Champagnat J, Fortin G, Thoby-Brisson M (2008). Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complex in vitro. European Journal of Neuroscience, Aug ;28(3):510-20. Pubmed.