Dynamic and Pathophysiology of Neuronal Networks

Leader

Research center

11 place Marcelin Berthelot
75231 Paris
Alain Prochiantz

Institution

Collège de France
CNRS
Inserm
ED158
Université Pierre et Marie Curie

Laboratory

Centre Interdisciplinaire Recherche Biologie
Phone: 01 44 27 12 26
UMR 7241 - U1050
LabEx MemoLife

Mots clefs

Synaptic plasticity
dopamine
Parkinson’s disease
neuronal networks
basal ganglia
GABAergic interneurons
endocannabinoids
Available to host a PhD student

publications

Valtcheva S, Venance L. Astrocytes gate Hebbian synaptic plasticity in the striatum. Nat Commun. 2016 Dec 20;7:13845. doi: 10.1038/ncomms13845. 

Cui Y, Paille V, Xu H, Genet S, Delord B, Fino E, Berry H, Venance L. Endocannabinoids mediate bidirectional striatal spike-timing dependent plasticity. J Physiol. 2015 Apr 15. doi: 10.1113/JP270324.

Paille V#, Fino E#, Du K, Morera-Herreras T##, Perez S#, Hellgren Kotaleski J & Venance L# (2013) GABAergic circuits control spike-timing-dependent plasticity. J Neurosci. 33:9353-9363.

Nelson MJ, Bosch C#, Venance L# & Pouget P (2013) Microscale inhomogeneity of brain tissue distorts electrical signal propagation. J Neurosci. 33(7):2821-7.

Bosch C#, Mailly P, Degos B#, Deniau JM# & Venance L #(2012) Preservation of the hyperdirect pathway of basal ganglia in a rodent brain slice. Neuroscience 215, 31-41.

Evans RC, Morera-Herreras T#, Cui Y#, Du K, Sheehan T, Kotaleski JH, Venance L# & Blackwell KT (2012) The effects of NMDA subunit composition on calcium influx and spike timing-dependent plasticity in striatal medium spiny neurons. PLoS Comput Biol. 8, e1002493.

Puente N, Cui Y#, Lassalle O, Lafourcade M, Georges F, Venance L#*, Grandes P* & Manzoni OJ* (2011) Polymodal activation of the endocannabinoid system in the extended amygdala. Nature Neuroscience 14(12), 1542-7. *: co-senior authors Pandolfo, P, Silveirinha, V, dos Santos-Rodrigues, A, Venance, L#, Ledent, C, Takahashi, RN, Cunha, RA & Köfalvi, A 2011

Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum?, Eur J Pharmacol. Vol.655(1-3), pp. 38-45.

Fields of research

Neurophysiology / systems neuroscience

Research Theme

 Our research is focused on encoding learning and memory in the basal ganglia, a set of subcortical nuclei implicated in the adaptive control of behavior. Reciprocally connected with the cerebral cortex and the limbic system, the basal ganglia participate to the detection of environmental cues and to the selection of appropriate actions based on motivation and expectancy of reward.

The pathological dysfunction of basal ganglia leads to major motor and cognitive disorders (Parkinson’s disease, OCDs Tourette’s syndrome, addiction…) for which no fully satisfying treatments are available yet.

We study various aspects of the dynamic organization and synaptic interactions underlying the dynamic properties of the basal ganglia network and the changes of these properties in animal models of human pathologies. We are using a multidisciplinary approach combining electrophysiology (in vitro multi-patch-clamp and in vivo recordings), fast-cyclic voltammetry, 2-photon imaging, single-cell RT-PCR and immunohistochemistry, using in vitro and in vivo model. The complementary conceptual and technical expertise of the members of the team together with the collaborations we already established with groups of mathematicians, molecular biologists, clinicians and pharmaceutical industry allow us to investigate the normal and pathological functions of the basal ganglia at the different levels of complexity of the neuronal network. 

1) The neuronal dynamics and synaptic plasticity (STDP) within the basal ganglia and cortical networks.

2) The neuron-glia crosstalk: we analyze the contribution of neurotransmitter uptake by astrocytes on corticostriatal information processing.

3) The physiology and pathophysiology of motor and cognitive properties link to dopamine and endocannabinoids. 

Lab rotation

Role of striatal interneurons in goal directed behavior

Chercheur responsable: 

VENANCE Laurent

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Basal ganglia are involved in goal-directed behavior and procedural learning. Striatum, the main input nucleus of basal ganglia, is composed of a majority of striatal projection neurons, but also of a variety of GABAergic interneurons which, and exert a strong feedforward inhibition. As we recently showed, GABAergic interneurons efficiently control synaptic hebbian plasticity (Paille et al., 2013, J Neurosci; Valtcheva et al., 2017, Neuropharmacol; Valtcheva and Venance, 2017, Nat Comm).

In this project we aim at optogenetically activating or inhibiting specifically each GABAergic subpopulation in dorsal striatum and observe the impact on a goal directed task and the associated procedural learning and recall. Neuronal activity in the behaving mice will be concomitantly examined with multi-channels recordings.

Techniques: in vivo optogenetics, behavioral tasks, in vivo multi-channel recordings, immunohistochemistry.

Contact

Collège de France - CIRB - 11, Place Marcelin Berthelot 75005 Paris - +33 1 44 27 12 26 - laurent.venance@college-de-france.fr

Superviseur: 

VENANCE Laurent & VANDECASTEELE Marie

Targeting GABAergic interneurons of the motor cortex as a therapeutic strategy in Parkinson's disease

Chercheur responsable: 

VENANCE Laurent

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

The target of our study is the inhibitory GABAergic neurons of the motor cortex. Indeed, recent evidence in human patients have questioned the classical model of Parkinson's disease, and indicate that cortical inhibition is reduced in PD. The potential beneficial effects of manipulating motor cortex inhibitory networks have never been directly assessed neither in humans nor in animal models of PD. Our results show that the high frequency stimulation of the subthalamic nucleus (HFS-STN), an efficient but costly therapeutic approach for Parkinson's disease which mechanisms remain largely elusive, involves the recruitment of cortical inhibitory networks. This project aims to evaluate the behavioral effect of the direct recruitment of cortical interneurons by optogenetics, as a potential alternative to HFS-STN or an adjunctive treatment.

Techniques: in vivo optogenetics, behavioral tasks, in vivo multi-channel recordings, immunohistochemistry.

Contact

Collège de France - CIRB - 11, Place Marcelin Berthelot 75005 Paris - +33 1 44 27 12 26 - laurent.venance@college-de-france.fr

Superviseur: 

VENANCE Laurent & DEGOS Bertrand

Dopaminergic control of cortical and thalamic interplay for striatal synaptic plasticity

Chercheur responsable: 

VENANCE Laurent

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018

Project

Basal ganglia are involved procedural learning and memory. Striatum, the main inputs nucleus of basal ganglia, acts as a coincidence detector of cortical and thalamic inputs. Dopamine tunes this striatal detection threshold. We have pioneered the field of spike-timing dependent plasticity, a synaptic Hebbian learning rule, at the level of basal ganglia (Fino et al., 2005, J Neurosci; Paillé et al., 2013, J Neurosci; Cui et al., 2016, eLife; Vlatcheva and Venance, 2017, Nat Comm). 

We are exploring the impact on striatal synaptic plasticity of cortical and thalamic activities timed with dopamine opto-stimulation or inhibition. This will be achieved in vitro and in vivo in physiological conditions and in a rodent model of Parkinson’s disease. This project aims at a better understanding how cortical and thalamic activity together with dopamine concurred to striatal synaptic plasticity and the engram of procedural learning.Techniques: electrophysiology (ex vivo patch-clamp), 2-photon imaging, optogenetics, multi-channel recordings.

Contact

Collège de France - CIRB - 11, Place Marcelin Berthelot 75005 Paris - +33 1 44 27 12 26 - laurent.venance@college-de-france.fr

Superviseur: 

VENANCE Laurent