Neurotransmission and signaling


Research center

17 rue du Fer à Moulin
75005 Paris


Université Pierre et Marie Curie
Université Pierre et Marie Curie


Marianne Coutures
UMRS 839
Contrat ANR, Brixham Foundation Prize (FRM, 2016)


- Pelosi A, Menardy F, Popa D, Girault JA, Hervé D. Heterozygous Gnal mice are a novel animal model to study dystonia pathophysiology. J Neurosci. 2017, 37:6253-67. 

- Giralt A, Brito V, Chevy Q, Simonnet C, Otsu Y, Cifuentes-Díaz C, de Pins B, Coura R, Alberch J, Ginés S, Poncer JC, Girault JA. Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model. Nat Commun. 2017, 8:15592.

- Engmann O, Giralt A*, Gervasi N*, Marion-Poll L, Gasmi L, Filhol O, Picciotto MR, Gilligan D, Greengard P, Nairn AC, Hervé D, Girault JA. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nature Commun, 2015, Dec 7;6:10099.

- Li L*, Gervasi N*, Girault JA.  Dendritic geometry shapes neuronal cAMP signaling to the nucleus. Nature Comm, 2015, 6:6319.

- Brami-Cherrier K, Gervasi N, Arsenieva D, Walkiewicz K, Boutterin MC, Ortega A, Leonard PG, Seantier B, Gasmi L, Bouceba T, Kadaré G, Girault JA*, Arold S*.  Dimerization controls activation of kinase-dependent functions of FAK at focal adhesions. EMBO J, 2014, 33:356-7.
*Equal contribution

Fields of research

Neuropharmacology / cell signaling

Research Theme

Our goal is to identify signaling mechanisms that underlie brain plasticity leading to long-lasting behavioral alterations. Our major model of study is the striatum that plays a crucial role in the control of movements, motivated behaviors, formation of habits, and procedural memory. The striatum is involved in several neurological and psychiatric diseases including Parkinson disease and addiction. Dopamine controls the acute function of striatal neurons and their long-lasting plasticity, thus contributing to reinforcement learning.

Drugs of abuse divert these processes by directly increasing dopamine transmission. Similar mechanisms are involved in side effects of L-DOPA in Parkinsonian patients. We study signaling pathways controlled by dopamine, glutamate, endocannabinoids and other neurotransmitters, which involve G proteins, protein kinases, phosphatases and gene expression. We attempt to identify the role of these pathways in simple behaviors and to identify assemblies of neurons in which they are activated. We also investigate other signaling pathways including non-receptor tyrosine kinases of the FAK family.

Lab rotation

Synaptic plasticity-induced ERK dynamics in striatal projection neurons

Team leader: 

GIRAULT Jean Antoine


July 9, 2018 - September 28, 2018

Application deadline: 

July 9, 2018


~ July-Sept 2018


The striatum is a major entry structure of the basal ganglia. It receives a convergent excitatory glutamate input (from cortex and thalamus), controlled by dopamine (DA) released. DA receptors are segregated into distinct neuronal populations in the striatum, D1R expressing SPN and D2R SPN. In D1-SPN, the extracellular signal-regulated kinase (ERK) kinase pathway can detects combination of glutamate and dopamine release and is essential for long-lasting modifications. In addition, striatal plasticity is significantly altered in pathological conditions in which either a loss of DA innervation (Parkinson’s disease) or aberrant DA release (drug addiction and L-DOPA induced dyskinesia) occurs. 

The spatiotemporal activation of ERK pathways in D1 SPN in responses to synaptic plasticity relevant activation is unknown. To gain deeper insights ERK pathway dynamics in SPN, we will combine multiphoton microscopy with FRET biosensors, pharmacological stimulation and/or LTP induction in adult mice striatal slices. The project will start by using pharmacological stimulation like D1R and/or glutamatergic receptor agonist to activate ERK pathway. The expected results will show that co-stimulation produce a synergistic activation of ERK pathway. The next step will be to test different long-term plasticity protocols and to record using multiphoton imaging ERK dynamics in SPN. We will also use pharmacological inhibition of the ERK pathway (by U0126) to understand if specific ERK activation are involved in LTP induction or maintenance.

The mechanisms involved in the induction of striatal LTP appears to be extremely complex. We think that imaging intracellular signalling pathways will help to understand the discrepancy between various LTP protocols. And extract the central role of ERK dynamics in the long term regulation of SPNs.


Institut du Fer à Moulin  - 17, rue du Fer à Moulin 75005 PARIS-