Physiologie et physiopathologie de la moelle épinière

Leader

Research center

45 rue des Saints Pères
75006 Paris
Daniel Zytnicki

Institution

CNRS
Université Paris Descartes
ED3C

Laboratory

UMR8119

Mots clefs

ALS
electrophysiology in vivo and in vitro
spinal cord circuitry
motoneuron
Renshaw cell
Available to host a PhD student

publications

Leroy F, Lamotte d'Incamps B, Zytnicki D. Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice. J Neurophysiol. 2015 Sep;114(3):1963-73. doi: 10.1152/jn.00193.2015. Epub 2015 Aug 12.

Leroy F#, Lamotte d'Incamps B#, Imhoff-Manuel RD#, Zytnicki D#. (2014) Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis. Elife Oct14;3. doi: 10.7554/eLife.04046.

Lamotte d’Incamps B#, Ascher P. (2014) High affinity and low affinity heteromeric nicotinic acetylcholine receptors at central synapses. J Physiol. Oct 1;592(Pt 19):4131-6

Delestrée N#, Manuel M#, Iglesias C, Elbasiouny SM, Heckman CJ, Zytnicki D#. (2014) Adult spinal motoneurones are not hyperexcitable in a mouse model of inherited amyotrophic lateral sclerosis. J. Physiol. Apr 1;592(Pt 7):1687-703

Ritter LK, Tresch MC, Heckman CJ, Manuel M#, Tysseling VM. (2014) Characterization of motor units in behaving adult mice shows a wide primary range. J Neurophysiol. Aug 1;112(3):543-51

Manuel M#, Zytnicki D#, Meunier C. (2014) The dendritic location of the L-type current and its deactivation by the somatic AHP current both contribute to firing bistability in motoneurons. Front Comput Neurosci. Jan 27;8:4.

Fields of research

Neurophysiology / systems neuroscience

Research Theme

Our team investigates the relationships between spinal motoneurons and the muscle fibers they are targeting, and how thisrelationship is altered in the context of a human degenerative disease of motoneurons (ALS). To do so, we have recently pioneeredtwo new preparations that allow studying the electrophysiological properties of identified spinal motoneurons.

Marin Manuel and Daniel Zytnicki have developed an in vivo preparation in which it is possible to study, for the first time in mice, notonly the motoneuron function but also their connection to their muscle fibers and their motor output (Manuel et al. J Neurosci 2009;Manuel et Heckman, 2011). It also allows us to understand how the electrical properties of motoneurons and the contractile propertiesof muscle fibers match each other. In addition, intracellular labelling of investigated motoneurons allow us to couple theelectrophysiological study with the study of some of them molecular properties (In Situ Hybridization, Immunocytochemistry).

At the same time, Boris Lamotte d’Incamps (in collaboration with P. Ascher, Lamotte d’Incamps et al. J Neurosci 2012) developed anin vitro preparation in which it is possible to perform patch-clamp recordings of functionally identified motoneurons (through antidromicstimulation of a ventral rootlet) and Renshaw cells (exhibiting a monosynaptic EPSC in response to the same stimulation). This wasachieved in lumbar slices of neonatal mice. Finally, the in vitro approach is also used to study the electrophysiological properties ofmotoneurons derived from IPSCs (Induced Pluripotent Stem Cells) obtained from ALS patients as well as healthy individuals(collaboration D. Bohl, I.C.M.).Thanks to our two novel preparations, we started to investigate the electrophysiological properties of mouse spinal motoneurons. Thiswork has been achieved in adults (in vivo experiments) and during the 2nd post-natal week (in vitro experiments). Our work in wildtype (WT) animals (Manuel et al. J Neurosci 2009, Iglesias et al. J Neurosci 2011) built solid ground on which we have now startedinvestigating transgenic mice, models of a human degenerative disease of motoneurons: Amyotrophic Lateral Sclerosis (ALS)(Collaborations CJ Heckman, Northwestern University, NIH-NINDS grant; George Mentis and Neil Schneider, Columbia University,Target ALS grant).

Recently, we identified the electrophysiological pattern of firing of two populations of motoneurons in neonates in vitro.Electrophysiological, electrical and molecular properties allow us to ascribe these two populations of motoneurons to innervating Fastcontracting muscle fibers and Slow contracting muscle fibers, respectively. In contrast with the generally accepted hypothesis, weshow that, in neonates, S type motoneurons (that do not degenerate in ALS) are hyperexcitable whereas the excitability of F typemotoneurons is unchanged (Leroy et al, eLife 2014). On the other hand, in adults, before the onset of neuromuscular degeneration, alarge fraction of F type motoneurons become hypoexcitable (Delestrée et al. J Physiol 2014).

Membres de l'équipe

Boris Lamotte d'Incamps,
Marin Manuel
Rebecca Manuel

Lab rotation

Electrophysiological investigation of spinal motor circuits in mouse models of Amyotrophic Lateral Sclerosis

Chercheur responsable: 

ZYTNICKI Daniel

Dates: 

1 September 2016 - 30 June 2017

Date limite de candidature: 

1 September 2016

Lab rotation proposal

~ Sep-Dec 2016 ~ Jan-March 2017 ~ Apr-June 2017

Project:

Amyotrophic Lateral Sclerosis is a neurodegenerative disease that affects motor neurons. We are investigating 1) the alterations of spinal motor circuits and electrical properties of motor neurons in this disease and 2) whether these alterations can lead to the degeneration of motor neurons. To answer these questions we are mainly using electrophysiological methods.

Address: Cen­tre de Neu­ro­physique, Phys­i­olo­gie et Patholo­gie - Uni­ver­sité Paris Descartes - 45 rue des Saints-Pères 75270 Paris cedex 06

Phone number:+33 1 42 86 22 85  ; Emaildaniel.zytnicki@parisdescartes.fr

Website

Superviseur: 

Marin MANUEL & Daniel ZYTNICKI