Neurophy Lab - Serge Schiffmann

Serge Schiffmann

M.D, PhD

The research of our team targets the cellular and network mechanisms that underlie motor control and motor skill learning or the encoding of procedural learning. The Basal Ganglia (BG) network is crucial in these processes constituting an interconnected neural network involved in adaptive control of behaviour. Basal ganglia are deeply disturbed in human diseases characterized by either movement disorders as Parkinson’s and Huntington’s diseases or by cognitive defects as in drug addiction. Our projects aim to identify the involvement in BG functions and dysfunctions of specific neuronal populations, as the Medium Spiny Neurons (iMSNs and dMSNs) in the matrix and striosomes of the striatum or the prototypical and arkypallidal neurons of the Globus pallidus. 

In this frame, we addressed the following questions: How do changes and differences in neuronal excitability, synaptic transmission and synaptic plasticity underlie functions of neurons populations in the different striatal compartments? How the globus pallidus neuronal populations’ connections and properties are modified in models of BG diseases? What are the roles and mechanisms of actions of regulatory neurotransmitter systems as adenosine and glycine and their relations to dopamine in the striatum? 

The team combines molecular, cellular and network level analysis by using ex vivo patch clamp electrophysiology, chemo- and optogenetics tools and behavioural analysis.

Selected Publications

mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice. 
Rial D., Puighermanal E., Chazalon M., Valjent E., Schiffmann* S.N., de Kerchove d´Exaerde* A. Biological Psychiatry, 88:945-954, 2020. 
Comment from the Editor: mTOR signalling regulates striatal function, Biological Psychiatry, 88:889, 2020. (*equal contribution). 
DOI 10.1016/j.biopsych.2020.05.029

Ablation of striatal somatostatin interneurons affects MSN morphology and electrophysiological properties, and increases cocaine-induced hyperlocomotion in mice. 
Gazan A., Rial D., Schiffmann S.N. European Journal of Neuroscience. 51(6):1388-1402, 2020. 
Featured Paper Commentary : Assous M., Emergence of novel functions in striatal Low Threshold Spike Interneurons. European Journal of Neuroscience, 2019 Dec 28. 
DOI 10.1111/ejn.14581

GPRIN3 controls neuronal excitability, morphology and striatal-dependent behaviors in the indirect pathway of the striatum. 
Karadurmus D., D. Rial, J.-F. De Backer, D. Communi, A. de Kerchove d´Exaerde, S.N. Schiffmann  Journal of Neuroscience, 39(38): 7513-7528, 2019. 
DOI 10.1523/JNEUROSCI.2454-18.2019

Alpha2-containing glycine receptors promote neonatal spontaneous activity of striatal medium spiny neurons and support maturation of glutamatergic inputs.  
Comhair J., J. Devoght, G. Morelli, R.J. Harvey, V. Briz, S.C. Borrie, C. Bagni, J.-M. Rigo, S.N. Schiffmann, D. Gall, B. Brone, S.M. Molchanova. Frontiers in Molecular Neuroscience, 11: 380. 2018. 
DOI 10.3389/fnmol.2018.00380

Deletion of Maged1 in mice abolishes locomotor and reinforcing effets of cocaine.  
De Backer J.-F., S. Monlezun, B. Detraux, A. Gazan, L. Vandopdenbosch, J. Cheron, G. Cannazza, S. Valverde, L. Cantacorps, M. Nassar, L. Venance, O. Valverde, P. Faure, M. Zoli, O. De Backer, D. Gall, S.N. Schiffmann, A. de Kerchove d’Exaerde. EMBO reports, 19: e45089, 1-17, 2018. 
DOI 10.15252/embr.201745089

Tonically Active α2 Subunit-Containing Glycine Receptors Regulate the Excitability of Striatal Medium Spiny Neurons. 
Molchanova S.M., Comhair J, Karadurmus D, Piccart E, Harvey R.J, Rigo J-M, Schiffmann SN, Brone B, Gall D. Frontiers in Molecular Neuroscience, 10:442. 2018. 
DOI 10.3389/fnmol.2017.00442

Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors. 
Lambot L., Chaves Rodriguez E., Houtteman D., XLi Y., Schiffmann S.N., Gall D.,Xde Kerchove d’Exaerde A. Journal of Neuroscience, 36(18):4976–4992, 2016. 
DOI 10.1523/JNEUROSCI.2717-15.2016

Modulation of ciliary phosphoinositide content regulates trafficking and Sonic Hedgehog signaling output. 
Chavez M, Ena S., Van Sande J., de Kerchove d’Exaerde A., Schurmans S., Schiffmann S.N. Developmental Cell, 34, 338-350, 2015. 
DOI 10.1016/j.devcel.2015.06.016

Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities. 
Wöhr M, Orduz D, Gregory P, Moreno H, Khan U, Vörckel Kj, Wolfer Dp, Welzl H, Gall D, Schiffmann SN, Schwaller B. Translational Psychiatry. 5:e525, 2015. 
DOI 10.1038/tp.2015.19

FACS-array profiling identifies Ecto-5’ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. 
Ena S., J.-F. De Backer, S.N. Schiffmann*,  A. de Kerchove d’Exaerde* Journal of Neuroscience, 33(20), 8794–8809, 2013. (*equal contribution). 
DOI 10.1523/JNEUROSCI.2989-12.2013

Neuronal Nogo-A negatively regulates dendritic morphology and synaptic transmission in the cerebellum. 
Petrinovic M.M., Hourez R., Aloy, E.M, Dewarrat G., Gall D., Weinmann O., J. Gaudias, L.C. Bachmann S.N. Schiffmann, K.E. Vogt, M.E. Schwab.  Proceedings of the National Academy of Sciences. USA, 110(3), 1083-1088, 2013. 
DOI 10.1073/pnas.1214255110

Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions.
Durieux P.F., S.N. Schiffmann*, A. de Kerchove d’Exaerde* EMBO Journal, 31, 640–653, 2012 (*equal contribution). 
DOI 10.1038/emboj.2011.400

Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1. 
Hourez R, Servais L, Orduz D., Gall D, Millard I, de Kerchove d’Exaerde A, Cheron G, Orr Ht, Pandolfo M, S.N. Schiffmann. Journal of Neuroscience, 31(33), 11795–11807, 2011. 
Comment from the Editor: Blocking IKA Ameliorates Spinocerebellar Ataxia, Journal of Neuroscience, 31(33), i-i, 2011.
DOI 10.1523/JNEUROSCI.0905-11.2011

D2R Striatopallidal neurons inhibit both locomotor and drug reward processes. 
Durieux P.F., Bearzatto B, Buch T, Waisman A, S.N. Schiffmann*, de Kerchove d’Exaerde* A. Nature Neuroscience, 12: 393-395, 2009 (*equal contribution). 
DOI 10.1038/nn.2286

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome. 
Servais L, Hourez R., Bearzatto B, Gall D., Schiffmann SN*, Cheron G*. Proceedings of the National Academy of Sciences. USA, 104: 9858–9863, 2007. (*equal contribution). 
Comment from the Editor: Purkinje cell abnormalities in fetal alcohol syndrome, P.N.A.S. USA, 104: 9547-9548.] 
DOI 10.1073/pnas.0607037104

Impaired motor coordination and Purkinje cells excitability in mice lacking calretinin.  
Schiffmann S.N., Cheron G., Lohof A., D’Alcantara P., Meyer M., Parmentier M., Schurmans S. Proceedings of the National Academy of Sciences. USA, 96: 5257-5262, 1999.
DOI 10.1073/pnas.96.9.5257