Lights-on Locomotion: optogenetic dissection of spinal circuits underlying locomotion in Vertebrates

Leader

Research center

47 bld de l'Hôpital
75651 Paris
Alexis Brice

Institution

Inserm
CNRS
Université Pierre et Marie Curie
ED158
Université Pierre et Marie Curie

Laboratory

UMRS 1127 UMR 7225
IHU-A-ICM

Mots clefs

behavior
Optogenetics
Locomotion
Circuit-breaking
Spinal cord
 

publications

Böhm UL, Prendergast A, Djenoune L, Nunes Figueiredo S, Gomez J, Stokes C, Kaiser S, Suster M, Kawakami K, Charpentier M, Concordet JP, Rio JP, Del Bene F, Wyart C. CSF-contacting neurons regulate locomotion by relaying mechanical stimuli to spinal circuits. Nat Commun. 2016 Mar 7;7:10866. doi: 10.1038/ncomms10866.

Sternberg JR, Wyart C. Neuronal wiring: linking dendrite placement to synapse formation. Curr Biol. 2015 Mar 2;25(5):R190-1. doi: 10.1016/j.cub.2015.01.006.

Mirat O, Sternberg JR, Severi KE, Wyart C. ZebraZoom: an automated program for high-throughput behavioral analysis and categorization. Front Neural Circuits. 2013 Jun 12;7:107. doi: 10.3389/fncir.2013.00107. eCollection 2013.

Warp E, Agarwal G, Wyart C, Friedmann D, Oldfield CS, Conner A, Del Bene F, Arrenberg AB, Baier H, Isacoff EY.Current Biology. 2012;22(2):93-102.

DelBene F, Wyart C, Robles E, Tran A, Looger L, Scott EK, Isacoff EY, Baier H. Science.2010;330(6004):669-73.

Janovjak H, Szobota S, Wyart C, Trauner D, Isacoff EY.Nat Neurosciences 2010;13(8):1027-32.

Wyart C, Del Bene F, Warp E, Scott EK, Trauner D, Baier H, Isacoff EY. Nature. 2009;461(7262):407-10.

Pautot S, Wyart C, Isacoff EY. Nat Methods. 2008 Aug;5(8):735-430

Fields of research

Computational neurosciences / neural theory

Research Theme

Sensory systems transduce fluctuations in the physical world into patterns of action potentials which are integrated to control motor outputs. Locomotion relies on genetically determined circuits constituted by spinal interneurons and capable of generating oscillations. Local sensory information about the outside world or the internal state seem to alter thesemotor patterns by triggering, stopping or steering locomotion. Although the advent of modern physiology shed some light on the connections of sensory cells and interneurons, most studies were limited to paralyzed preparations where local sensory inputs could not be active. So how are local mechano-, chemo-, and thermo-sensory inputs dynamically recruited in moving animals? And how are they integrated by assemblies of interneurons during locomotion? To elucidate these questions, I propose to study dynamic sensory-motor integration in spinal circuits of the tractable genetic model organism, zebrafish. The transparency of the larva enables to measure and manipulate sensory inputs with light in moving animals. In previous work, we developed in vivo optogenetic approaches for probing spinal circuits.

We identified a new proprioceptive pathway interfacing the spinal circuits with the cerebrospinal fluid (CSF). We demonstrated that remote activation of this pathway could trigger slow locomotion. We will now combine optogenetics, population imaging, physiology and quantitative analysis of behaviour in order to elucidate this novel proprioceptive function at the molecular level (Aim 1). We will extend our approach to other sensory pathways in order to unravel when sensory inputs are recruited and how they dynamically shape motor output in moving animals (Aim 2). Aim 3 will unravel how sensory inputs project and select motor patterns at the circuit level. Our studies should solve a fundamental question in neuroscience: how do spinal circuits integrate chemo- and mechano- and thermo-sensory information to produce complex motor patterns.

Lab rotation

Investigations of neuroimmune interactions at the interface with the cerebrospinal fluid

Chercheur responsable: 

WYART Claire

Dates: 

18 September 2017 - 30 March 2018

Date limite de candidature: 

30 March 2018

Period

~ Sept-Dec 2017

~ Jan-March 2018

Project

We will investigate the molecular and cellular pathways enabling to detect pathogen invasions in the cerebrospinal fluid, and modulating locomotion and posture as a function of the inflammation.

Contact

Institut du Cerveau et de la Moelle épinière - 47, boulevard de l'Hôpital 75013 Paris - +33 1 57 27 43 02 - claire.wyart@gmail.com

Superviseur: 

PRENDERGAST Andrew & WYART Claire