Our research:

On going Projects

Linking cellular metabolism and synapses

What signaling loops between mitochondria and synapses in the living brain?

Leaders: M Arango-Lievano, Y Dromard

J Neurosci. 2018;38(6):1335-1350. doi: 10.1523/JNEUROSCI.2793-17.2017.

Neural Plast. 2016;3985063. doi: 10.1155/2016/3985063.

J Neurosci. 2004;24(35):7614-22 PMID: 15342727

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Comorbidity between stress and Alzheimer’s disease

Role of glucocorticoid resistance on the impact of stress-induced neuropathology?

Leaders: Y Dromard, M Arango-Lievano

J Vis Exp.  2016;(118). doi: 10.3791/54796

Neurobiol Dis. 2016;88:107-17. doi: 10.1016/j.nbd.2016.01.001.

Experience & activity-dependent glucocorticoid signaling in brain networks

A mechanism to change stress response in engram cells? What physiological function for the pro-domain of neurotrophic factors?

Leaders: F Jeanneteau, Prabahan Chakraborty

Neuroendocrinology. 2019;109(3):277-284 doi: 10.1159/000496392.
Pharmacol Res. 2016;113(Pt A):1-17 doi: 10.1016/j.phrs.2016.08.005.
Neuroscience. 2013;239:173-95 doi: 10.1016/j.neuroscience.2012.09.017
Mol Cell Biol. 2013;33(18):3700-14. doi: 10.1128/MCB.00150-13
PNAS 2012;109(4):1305-10. doi: 10.1073/pnas.1114122109

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Capturing the synaptic trace of memory and plasticity to the changing environment

In vivo imaging of dendritic spines reveals plasticity rules of synaptic maps in various environmental contexts.

Leaders: M Arango-Lievano

PNAS 2015;112(51):15737-42. doi: 10.1073/pnas.1509045112.

Functional neuroanatomy of the social brain networks in autism

Is there a dialogue between oxytocin and vasopressin neurocircuit to integrate social signals?

Leaders: D Huzard, A Borie, M Desarmenien,

New fluorescent peptides to study vasopressin and oxytocin receptors

How to visualize receptors for vasopressin and oxytocin in the normal and diseased brain?

Leaders: G Guillon, M Corbani

Gen Comp Endocrinol. 2018;258:15-32. doi: 10.1016/j.ygcen.2017.10.011
Pharmacol Res. 2016;113(Pt A):257-264. doi: 10.1016/j.phrs.2016.08.027
J Neuroendocrinol 2012;24(4):609-28 doi: 10.1111/j.1365-2826.2012.02303

Brain-Fat Axis

Role of nutrition on the synaptic trace of memory?

Leaders: M Atouf Ghazi, Y Dromard

F1000Res. 2017;6:1208. doi: 10.12688/f1000research.11375.1

Past Projects:

Dopamine receptor variant in essential tremor

Prevalence and mechanism?

Leaders: F Jeanneteau

PNAS 2006;103(28):10753-8 PMID: 16809426

Biased signaling of dopamine receptors

Does the allosteric change mediated by palmitoylation influence protein-protein interaction and signaling?

Leaders: F Jeanneteau

Mol Cell Biol. 2016;36(6):1019-31. doi: 10.1128/MCB.00916-15.

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MKP-1 (dusp1) in neuronal plasticity

How a suppressor of growth factor signaling influence neuronal networks involved in behavioral adaptation to changing environment?

Leaders: F Jeanneteau, M Arango-Lievano

Sci Rep. 2016;6:37231. doi: 10.1038/srep37231.
Commun Integr Biol. 2011;4(3):281-3. doi: 10.4161/cib.4.3.14766.
Nat Neurosci. 2010;13(11):1373-9. doi: 10.1038/nn.2655.

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Imaging of pericytes functional dynamics in the living brain

Pericytosis in neuropathologies of the CNS?

Leaders: M Arango-Lievano

Cell Rep. 2018;23(4):1045-1059. doi: 10.1016/j.celrep.2018.03.110.

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Synoposis

A priority of the team is to clarify how hormones involved in cellular communication control key biological functions and how their dysfunction leads to pathological states. We perform longitudinal studies side by side in human patients as well as in new model non-human organisms for reaching predictability of disease trajectories and modification. This is a formidable challenge that depends on specific approaches to capture with minimal invasiveness, real time and multimodal observations notably in the practices of live in vivo microscopy, telemetric electrophysiological recordings, ethological inspection of behaviors and optogenetic or chemogenetic manipulations in freely behaving animal models. We developed such expertise over the years and move forward to explore the limits of brain networks remodeling plasticity at different organizational scales (e.g. molecules, cells, networks, organism).

The diversity of responses to stress hormones among individuals and within organs, tissues and cells is shaped by age, gender, genetics, metabolism, and the quality or quantity of exposure. However, such factors cannot explain the heterogeneity of responses in the brain within cells of the same lineage, or similar tissue environment, or in the same individual. We propose to investigate how the stress response is continuously updated by synchronized neural activity on large-scale brain networks. This occurs at the molecular, cellular and behavioral levels by crosstalk between activity-dependent and stress hormone signaling pathways, which shapes the diversity of responses based on prior experience. Such a Bayesian optimization determines (mal)adaptation to the demands of the brain, body and the external world.

The first axis of research in the lab is to understand how the diversity of glucocorticoid response throughout brain neuronal networks is essential for supporting optimal health, while its disruption may contribute to the pathophysiology of stress-related disorders, such as major depression, and resistance to therapeutic treatments. Hypothetical framework is that chronic stress accelerates the maturation/aging of neural systems in brain regions serving proximal functions while suppressing development of systems in centers supporting functions relevant later in life. Risk vs. resilience to mental disorders depends on multi-scales, long-term changes of brain development (e.g. circuits, molecules). This has tremendous implications for predicting behavioral coping styles and treatment efficacy.

The second axis of research is the ontogeny of the social brain network particularly sensitive to developmental periods and the influence of stress. Early in life, an interaction of susceptibility gene variants with stress can lead to social anxiety later in life, imposing heavy burden on society. At present, quantitative biomarkers for early diagnosis and long-term assessment of social anxiety do not exist. Without such objective biomarkers, diagnosis, monitoring and treatment adjustments rely exclusively on suboptimal clinical examination. Our goal is to develop sensitive and reliable diagnostic tests to predict the efficacy of treatments that may take months or years to manifest.

5 major publications

1: Arango-Lievano M, Borie AM, Dromard Y, Murat M, Desarmenien MG, Garabedian MJ, Jeanneteau F. Persistence of learning-induced synapses depends on neurotrophic priming of glucocorticoid receptors. Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):13097-13106. doi: 10.1073/pnas.1903203116

2: Arango-Lievano M, Boussadia B, De Terdonck LDT, Gault C, Fontanaud P, Lafont C, Mollard P, Marchi N, Jeanneteau F. Topographic Reorganization of Cerebrovascular Mural Cells under Seizure Conditions. Cell Rep. 2018 Apr 24;23(4):1045-1059. doi: 10.1016/j.celrep.2018.03.110

3: Jeanneteau F, Barrère C, Vos M, De Vries CJM, Rouillard C, Levesque D, Dromard Y, Moisan MP, Duric V, Franklin TC, Duman RS, Lewis DA, Ginsberg SD, Arango-Lievano M. The Stress-Induced Transcription Factor NR4A1 Adjusts Mitochondrial Function and Synapse Number in Prefrontal Cortex. J Neurosci. 2018  Feb 7;38(6):1335-1350. doi: 10.1523/JNEUROSCI.2793-17.2017

4: Arango-Lievano M, Lambert WM, Bath KG, Garabedian MJ, Chao MV, Jeanneteau F. Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment. Proc Natl Acad Sci U  S A. 2015 Dec 22;112(51):15737-42. doi: 10.1073/pnas.1509045112

5: Jeanneteau F, Lambert WM, Ismaili N, Bath KG, Lee FS, Garabedian MJ, Chao MV. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1305-10. doi: 10.1073/pnas.1114122109

Current Lab members

Freddy Jeanneteau                                             Chercheur                                               CNRS

Gilles Guillon                                                       DR1-e                                                     CNRS

Pascal Colson                                                     PUPH                                                      CHU

Damien Huzard                                                   Postdoc                                                   Inserm-FRM

Yann Dromard                                                    Engineer                                                 Inserm-France Alzheimer

Fanny Andreu                                                     Pharmacy                                                CHU

Prabahan Chakraborty                                        Postdoc                                                   NIH-Inserm

Maryam Atouf Ghazi                                           Master 2                                                  Inserm-FRC

Past lab members

Michel Desarmenien                                           DR2 CNRS                                             (retired)

Maithe Corbani                                                   Chercheur CNRS                                    (retired)

Vera Boulay                                                         Engineer INSERM                                  (retired)

Margarita Arango-Lievano                                  Postdoc                                                   (now R&D at Canon)

Geraldine Petit                                                    Postdoc                                                   (now R&D at OT4B)

Elisabete Augusto                                               Postodc                                                   (now Postdoc at Magendie Bordeaux)

Amelie Borie                                                        PhD student                                            (now postdoc at Emory Univ)

Maxime Maniere                                                 PhD student                                            (now ?)

Emilie Maruhenda                                               M2 student                                              (now postdoc in Oxford U)

Matthias Catteau                                                 M2 student                                              (now PhD in Montpellier)

Cedric Bertrand                                                  M2 student                                              (now PhD in Amiens)

Maria Moreno                                                      M2 student                                              (now PhD in Montpellier)

Lucile Du Trieu De Terdonck                              M2 student                                              (now PhD in Montpellier)

Djodi Dufner                                                        Pharmacy                                                (now Pharmacy Montpellier)

Cerebrovascular research

Cerebrovascular mural cells display a topographic reorganization.

Engram & Spine plasticity

Social behaviors

State-of-the-art analysis of social behaviors in mice models.