TEAM

Cellular interactions, neurodegeneration and neuroplasticity

Group leader : L. Kerkerian – Le Goff

Our team investigates the mechanisms of cellular interactions, neurodegeneration and neuroplasticity, in particular in the context of basal ganglia-related pathologies.

FOR BEGINNERS

Neurodegeneration is a progressive pathological process that triggers dysfunction and death of nerve cells. Many neurodegenerative disorders, including Parkinson’s disease, occur as a result of neurodegenerative processes whose causes are not fully elucidated. Understanding the pathological mechanisms leading to neurodegeneration (pathogenesis) and its consequences on the functioning of neural networks is essential for the development of curative or preventive treatments.

Progressive loss of dopamine neurons in the substantia nigra pars compacta (SNc delineated by dotted lines) after dysfunction of excitatory amino acid transporters

Progressive loss of dopamine neurons in the substantia nigra pars compacta (SNc delineated by dotted lines) after dysfunction of excitatory amino acid transporters

Neuroplasticity, also known as brain plasticity, refers to the capacity of the nervous system to adapt in response to experience and to internal or external stimulations by modifying the interactions between nerve cells (such as changes in the connections between neurons called “synapses” or in the activity) or by generating new nerve cells. This phenomenon is not limited to embryonic or post-natal development, but occurs all along the life. Neuroplasticity has been notably involved in learning and memory processes. It also occurs under pathological conditions or in response to chronic treatments. Such adaptive changes can either represent compensatory mechanisms counteracting the deficits triggered by neuronal dysfunction or death, or, on the contrary, participate in or even aggravate the deficits.

Parkinson’s disease is a progressive neurodegenerative disorder with high prevalence (second most common neurodegenerative disease after Alzheimer’s disease). The disease usually begins between the ages of 45 and 70. It is characterized by a triad of severe motor symptoms but is also associated with a set of non-motor symptoms. One main neuropathological feature of Parkinson’s disease is the loss of neurons located in a deep brain region, called locus niger or substantia nigra. These neurons, which use dopamine as a neurotransmitter, notably regulate the activity of the basal ganglia, a set of brain structures involved in motor learning and movement control. The neurodegenerative process will lead to compensatory hyperactivity of dopamine neurons not yet affected, but also to a cascade of structural and functional reorganizations within the basal ganglia network and interacting brain structures, which generates the cardinal symptoms of the disease (pathophysiology). Long-term treatments can also trigger adaptive changes underlying the maintenance of their beneficial effects or, on the contrary, the appearance of side effects. Characterizing these adaptive changes in Parkinson’s disease and in response to its current treatments could provide a basis for the development of future therapeutic strategies. Our primary aim is to better understand the normal and pathological functioning of the basal ganglia with a focus on Parkinson’s disease, but also in the context of autism spectrum disorders in collaboration with Laurent Fasano’s team at the Institute, through studies on animal models (rat, mouse, Drosophila). Our work also concerns other pathologies, such as Charcot-Marie-Tooth disease or Alzheimer’s disease.

Visualisation des neurones dopaminergique de la substance noire et de leur environnement astrocytaire par double immunodetection de la tyrosine hydroxylase et du transporteur glial des acides aminés excitateurs GLT1. Illustration: Ⓒ Jean-Pierre Kessler, IBDM, Marseille

Visualisation of nigral dopaminergic neurons and their astrocytic environment by dual immunodetection of the dopamine synthetizing enzyme tyrosine hydroxylase and of the glial excitatory aminoacid transporter GLT1
Illustration: Ⓒ Jean-Pierre Kessler, IBDM, Marseille

 

FOR SPECIALISTS

The team combines multilevel expertise and skills to study synaptic transmission, neurodegeneration and neuroplasticity in the adult brain, using rodent and Drosophila models. The central interest is on basal ganglia (BG)-related functions and pathologies, with focus on the pathophysiology and treatment of Parkinson’s disease (PD), which is characterized by the degeneration of the nigrostriatal dopaminergic neurons. Ongoing research lines have three main objectives:

  1. Gain knowledge on the anatomofunctional organization of the BG network and its remodeling in pathological condition, which may help design novel symptomatic treatment; the current work is centered on striatal cholinergic interneurons and corticostriatal synaptic function/plasticity.

    Optogenetic control of striatal cholinergic interneurons. Double labeling, in the striatum of transgenic mice, of the striatal output neurons expressing the dopamine D1 receptor (fused to tdTomato; red fluorescence) and the cholinergic interneurons in which halorhodopsin expression (eNpHR) allowing their photo-inhibition has been driven (fused to EYFP; green fluorescence). The electrophysiological trace illustrates the interruption, in one cholinergic interneuron, of the spontaneous spiking obtained when amber light is delivered into the striatum in these mice. Ⓒ Nicolas Maurice, IBDM, Marseille

    Optogenetic control of striatal cholinergic interneurons.
    Double labeling, in the striatum of transgenic mice, of the striatal output neurons expressing the dopamine D1 receptor (fused to tdTomato; red fluorescence) and the cholinergic interneurons in which expression of halorhodopsin (fused to EYFP; green fluorescence) has been driven to allow their photo-inhibition. The electrophysiological trace illustrates the interruption of the spontaneous spiking of one cholinergic interneuron obtained when amber light is delivered in vivo into the striatum of these mice.
    Ⓒ Nicolas Maurice, IBDM, Marseille

  2.  Identify molecular players in neuronal death processes or defense pathways against cellular stress that may represent new targets for disease-modifying strategies. Particular focus is made on the mechanisms regulating autophagy, mitochondrial dynamics and mitochondrial quality control via mitophagy, which are main players in neurodegenerative diseases. This research is performed in the context of PD, but also of Alzheimer’s disease and Charcot-Marie-Tooth disease type 2A.
  3. Identify disease-relevant anatomical targets for the surgical treatment by deep brain stimulation and evaluate the neuroprotective potential of this neurosurgical therapy.

We are also deeply involved in two collaborative projects developed by other IBDM teams.
One project aims at characterizing the neuronal substrates of the autistic syndrome linked to haploinsufficiency of TSHZ3, the gene encoding the transcription factor TSHZ3 (Laurent Fasano’s team). We are characterizing several transgenic mouse models with targeted conditional deletion of Tshz3 in components of the corticostriatal circuitry to define “where” and “when” the loss of Tshz3 is crucial for developing the core symptoms of ASD, by combining molecular, cellular, electrophysiological and behavioral approaches.

Traçage retrograde trans-synaptique d’un neurone épineux du striatum et des neurones du cortex cérébral projetant sur le striatum à l’aide du virus de la rage Ⓒ Pascal Salin, IBDM, Marseille

Retrograde transynaptic tracing of a striatal spiny neuron and of the cortical neurons projecting to the striatum using rabies virus
Ⓒ Pascal Salin, IBDM, Marseille

The other project aims at improving the efficacy and safety of the cell-based replacement therapy for PD using human induced pluripotent stem cells (hiPSCs) (Rosana Dono in Flavio Maina’s team). We are currently evaluating the potential of regulating the levels of glypican 4, a signaling modulator, as a strategy to foster hiPSCs differentiation towards the disease-relevant cell type, namely ventral midbrain dopamine neuron, and reduce their propensity to develop tumors upon brain transplantation in a rat PD model at different stages of in vitro differentiation.

Our approach combines the use or development of relevant experimental models in rodents (chronic deep brain stimulation, cell specific ablation, optogenetic or chemogenetic modulation of neuronal activity) with a variety of analytic tools, including behavioral tests, functional anatomy, tract-tracing, electrophysiology (on brain slices and in vivo), neurochemistry, and is implemented with genetics, imaging and molecular biology in Drosophila models.


Selected publications

PUBLICATION

Golgi staining-like retrograde labeling of brain circuits using rabies virus: Focus onto the striatonigral neurons

P Salin, D Blondel, L Kerkerian-Le Goff, P Coulon
J Neurosci Methods . 2020 Oct 1;344:108872. doi: 10.1016/j.jneumeth.2020.108872. https://pubmed.ncbi.nlm.nih.gov/32693000/

PUBLICATION

Reply to: Letter to the Editor by Martínez-Fernández

Yvan Vachez, Carole Carcenac, Robin Magnard, Lydia Kerkerian-Le Goff, Pascal Salin, Marc Savasta, Sebastien Carnicella, Sabrina Boulet
Mov Disord . 2020 Jun;35(6):1084-1085. doi: 10.1002/mds.28082 PMID: 32562462

PUBLICATION

Subthalamic Nucleus Stimulation Impairs Motivation: Implication for Apathy in Parkinson's Disease

Yvan Vachez, Carole Carcenac, Robin Magnard, Lydia Kerkerian-Le Goff, Pascal Salin, Marc Savasta, Sebastien Carnicella, Sabrina Boulet
Mov Disord . 2020 Apr;35(4):616-628. doi: 10.1002/mds.27953. Epub 2020 Jan 13. PMID: 31930749

PUBLICATION

Glutamate transporter 1-expressing glia in the rat substantia nigra-Morphometric analysis and relationships to synapses

Jean-Pierre Kessler, Pascal Salin, Lydia Kerkerian-Le Goff
Glia. 2020 Mar 14. doi: 10.1002/glia.23823. Online ahead of print. PMID: 32170887

PUBLICATION

Construct Validity and Cross Validity of a Test Battery Modeling Autism Spectrum Disorder (ASD) in Mice.

Roubertoux PL, Tordjman S, Caubit X, di Cristopharo J, Ghata A, Fasano L, Kerkerian-Le Goff L, Gubellini P, Carlier M.
Behav Genet . 2020 Jan;50(1):26-40. doi: 10.1007/s10519-019-09970-x. PMID: 31542842

PUBLICATION

Striatal Cholinergic Interneurons: How to Elucidate Their Function in Health and Disease

Nicolas Mallet, Arthur Leblois, Nicolas Maurice, Corinne Beurrier
Front Pharmacol. 2019 Dec 13;10:1488. doi: 10.3389/fphar.2019.01488. eCollection 2019. PMID: 31920670

PUBLICATION

PlexinD1 and Sema3E determine laminar positioning of heterotopically projecting callosal neurons.

Velona T, Altounian M, Roque M, Hocine M, Bellon A, Briz CG, Salin P, Nieto M, Chauvet S, Mann F.
Mol Cell Neurosci. 2019 Oct;100:103397. doi: 10.1016/j.mcn.2019.103397. PMID: 31454665

PUBLICATION

Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior

Chabbert D, Caubit X, Roubertoux PL, Carlier M, Habermann B, Jacq B, Salin P, Metwaly M, Frahm C, Fatmi A, Garratt AN, Severac D, Dubois E, Kerkerian-Le Goff L, Fasano L, Gubellini P.
Biol Psychiatry. 2019 Aug 15;86(4):274-285. doi: 10.1016/j.biopsych.2019.03.974. PMID: 31060802

PUBLICATION

Chronic fornix deep brain stimulation in a transgenic Alzheimer's rat model reduces amyloid burden, inflammation, and neuronal loss

Leplus A, Lauritzen I, Melon C, Kerkerian-Le Goff L, Fontaine D, Checler F.
Brain Struct Funct. 2019 Jan;224(1):363-372. doi: 10.1007/s00429-018-1779-x. PMID: 30341742

PUBLICATION

Opto nongenetics inhibition of neuronal firing

Ait Ouares K, Beurrier C, Canepari M, Laverne G, Kuczewski N
Eur J Neurosci. 2019 Jan;49(1):6-26. doi: 10.1111/ejn.14251. PMID: 30387216

PUBLICATION

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

Caubit X, Gubellini P, Andrieux J, Roubertoux PL, Metwaly M1, Jacq B, Fatmi A, Had-Aissouni L, Kwan KY, Salin P, Carlier M, Liedén A, Rudd E, Shinawi M, Vincent-Delorme C, Cuisset JM, Lemaitre MP10, Abderrehamane F, Duban B, Lemaitre JF, Woolf AS, Bockenhauer D, Severac D, Dubois E, Zhu Y, Sestan N, Garratt AN, Kerkerian-Le Goff L, Fasano L.
Nat Genet. 2016 Sep 26. PMID: 27668656

PUBLICATION

Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.

Ztaou S, Maurice N, Camon J, Guiraudie-Capraz G, Kerkerian-Le Goff L, Beurrier C, Liberge M, Amalric M.
J Neurosci. 2016 Aug 31;36(35):9161-72. PMID: 27581457

PUBLICATION

SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation

Zong-Bo Wei, Ye-Feng Yuan, Florence Jaouen, Mei-Sheng Ma, Chan-Juan Hao, Zhe Zhang, Quan Chen, Zengqiang Yuan, Li Yu, Corinne Beurrier, Wei Li
Autophagy . 2016 Jul 2;12(7):1168-79. doi: 10.1080/15548627.2016.1179402. PMID: 27171858

PUBLICATION

LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.

Tiveron MC, Beurrier C, Céni C, Andriambao N, Combes A, Koehl M, Maurice N, Gatti E, Abrous DN, Kerkerian-Le Goff L, Pierre P, Cremer H.
PLoS One. 2016 Jun 7;11(6):e0157052. PMID: 27272053

PUBLICATION

Metabolic, synaptic and behavioral impact of 5-week chronic deep brain stimulation in hemiparkinsonian rats.

Chassain C, Melon C, Salin P, Vitale F, Couraud S, Durif F, Kerkerian-Le Goff L, Gubellini P.
J Neurochem. 2016 Mar;136(5):1004-16. PMID: 26576509

PUBLICATION

Synaptic scaling up in medium spiny neurons of aged BACHD mice: A slow-progression model of Huntington's disease

Rocher AB, Gubellini P, Merienne N, Boussicault L, Petit F, Gipchtein P, Jan C, Hantraye P, Brouillet E, Bonvento G.
Neurobiol Dis. 2016 Feb;86:131-9. doi: 10.1016/j.nbd.2015.10.016. PMID: 26626081

PUBLICATION

Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex

Henry G S Martin, Axel Bernabeu, Olivier Lassalle, Clément Bouille, Corinne Beurrier, Anne-Laure Pelissier-Alicot, Olivier J Manzoni
Front Cell Neurosci . 2015 Dec 1;9:457. doi: 10.3389/fncel.2015.00457. PMID: 26648844

PUBLICATION

Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

Maurice N, Deltheil T, Melon C, Degos B, Mourre C, Amalric M, Kerkerian-Le Goff L.
PLoS One. 2015 Nov 16;10(11):e0142838. PMID: 26571268

PUBLICATION

Striatal Cholinergic Interneurons Control Motor Behavior and Basal Ganglia Function in Experimental Parkinsonism

Nicolas Maurice, Martine Liberge, Florence Jaouen, Samira Ztaou, Marwa Hanini, Jeremy Camon, Karl Deisseroth, Marianne Amalric, Lydia Kerkerian-Le Goff, Corinne Beurrier
Cell Rep. 2015 Oct 27;13(4):657-66. PMID: 26489458

PUBLICATION

Differential organization of cortical inputs to striatal projection neurons of the matrix compartment in rats.

Deng Y, Lanciego J, Goff LK, Coulon P, Salin P, Kachidian P, Lei W, Del Mar N, Reiner A.
Front Syst Neurosci. 2015 Apr 14;9:51. PMID: 25926776

PUBLICATION

Progressive brain metabolic changes under deep brain stimulation of subthalamic nucleus in parkinsonian rats.

Melon C, Chassain C, Bielicki G, Renou JP, Kerkerian-Le Goff L, Salin P, Durif F.
J Neurochem. 2015 Mar;132(6):703-12. PMID: 25533782

PUBLICATION

Reducing Glypican-4 in ES Cells Improves Recovery in a Rat Model of Parkinson's Disease by Increasing the Production of Dopaminergic Neurons and Decreasing Teratoma Formation.

Fico A, de Chevigny A, Melon C, Bohic M, Kerkerian-Le Goff L, Maina F, Dono R, Cremer H.
J Neurosci. 2014 Jun 11;34(24):8318-23. PMID: 24920634

PUBLICATION

Oxygen glucose deprivation-induced astrocyte dysfunction provokes neuronal death through oxidative stress.

Gouix E, Buisson A, Nieoullon A, Kerkerian-Le Goff L, Tauskela JS, Blondeau N, Had-Aissouni L.
Pharmacol Res. 2014 Jun 11;87C:8-17. PMID:24928737

PUBLICATION

Cellular and Behavioral Outcomes of Dorsal Striatonigral Neuron Ablation: New Insights into Striatal Functions.

Révy D, Jaouen F, Salin P, Melon C, Chabbert D, Tafi E, Concetta L, Langa F, Amalric M, Kerkerian-Le Goff L, Marie H, Beurrier C.
Neuropsychopharmacology. 2014 Jun 6. PMID:24903652

PUBLICATION

Distinct effects of mGlu4 receptor positive allosteric modulators at corticostriatal vs. striatopallidal synapses may differentially contribute to their antiparkinsonian action.

Gubellini P, Melon C, Dale E, Doller D, Kerkerian-Le Goff L.
Neuropharmacology. 2014 Oct;85:166-77. PMID:24866785

PUBLICATION

Tyrosine hydroxylase expression and activity in nigrostriatal dopaminergic neurons of MPTP-treated mice at the presymptomatic and symptomatic stages of parkinsonism

Elena A Kozina, Gulnara R Khakimova, Vitaly G Khaindrava, Valeriayn G Kucheryanu, Nadezhda E Vorobyeva, Alexey N Krasnov, Sophia G Georgieva, Lidiya Kerkerian-Le Goff, Michael V Ugrumov
J Neurol Sci . 2014 May 15;340(1-2):198-207. doi: 10.1016/j.jns.2014.03.028. PMID: 24768159

PUBLICATION

Progressive Parkinsonism by acute dysfunction of excitatory amino acid transporters in the rat substantia nigra

Maxime Assous, Laurence Had-Aissouni, Paolo Gubellini, Christophe Melon, Imane Nafia, Pascal Salin, Lydia Kerkerian-Le-Goff, Philippe Kachidian
Neurobiol Dis . 2014 May;65:69-81. doi: 10.1016/j.nbd.2014.01.011. PMID: 24480091

PUBLICATION

Spatial learning, monoamines and oxidative stress in rats exposed to 900 MHz electromagnetic field in combination with iron overload

Karima Maaroufi, Laurence Had-Aissouni, Christophe Melon, Mohsen Sakly, Hafedh Abdelmelek, Bruno Poucet, Etienne Save
Behav Brain Res . 2014 Jan 1;258:80-9. doi: 10.1016/j.bbr.2013.10.016. PMID: 24144546

PUBLICATION

Striatal molecular signature of subchronic subthalamic nucleus high frequency stimulation in parkinsonian rat.

Lortet S, Lacombe E, Boulanger N, Rihet P, Nguyen C, Goff LK, Salin P.
PLoS One. 2013 Apr 4;8(4):e60447 PMID: 23593219

PUBLICATION

Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson's disease treatment and dyskinesia.

Bennouar KE, Uberti MA, Melon C, Bacolod MD, Jimenez HN, Cajina M, Kerkerian-Le Goff L, Doller D, Gubellini P.
Neuropharmacology. 2013 Mar;66:158-69. PMID: 22491024

PUBLICATION

The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.

Jean A, Laurent L, Bockaert J, Charnay Y, Dusticier N, Nieoullon A, Barrot M, Neve R, Compan V.
Transl Psychiatry. 2012 Dec 11;2:e203. PMID: 23233022

PUBLICATION

The nucleus accumbens 5-HTR₄-CART pathway ties anorexia to hyperactivity.

Jean A, Laurent L, Bockaert J, Charnay Y, Dusticier N, Nieoullon A, Barrot M, Neve R, Compan V.
Transl Psychiatry. 2012 Dec 11;2:e203. PMID: 23233022

PUBLICATION

Portable microstimulator for chronic deep brain stimulation in freely moving rats.

Forni C, Mainard O, Melon C, Goguenheim D, Kerkerian-Le Goff L, Salin P.
J Neurosci Methods. 2012 Jul 30;209(1):50-7. PMID: 22659685

PUBLICATION

Antiparkinsonian action of a selective group III mGlu receptor agonist is associated with reversal of subthalamonigral overactivity.

Lopez S, Jouve L, Turle-Lorenzo N, Kerkerian-Legoff L, Salin P, Amalric M.
Neurobiol Dis. 2012 Apr;46(1):69-77. PMID: 22245662

PUBLICATION

High frequency stimulation of the subthalamic nucleus impacts adult neurogenesis in a rat model of Parkinson's disease.

Khaindrava V, Salin P, Melon C, Ugrumov M, Kerkerian-Le-Goff L, Daszuta A.
Neurobiol Dis. 2011 Jun;42(3):284-91. PMID: 21296669

PUBLICATION

The added value of rabies virus as a retrograde tracer when combined with dual anterograde tract-tracing.

López IP, Salin P, Kachidian P, Barroso-Chinea P, Rico AJ, Gómez-Bautista V, Conte-Perales L, Coulon P, Goff LK, Lanciego JL.
J Neurosci Methods. 2010 Dec 15;194(1):21-7. PMID: 20096304

PUBLICATION

Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.

Deniau JM, Degos B, Bosch C, Maurice N.
Eur J Neurosci. 2010 Oct;32(7):1080-91. PMID: 21039947

PUBLICATION

Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate receptors.

Quintana A, Melon C, Kerkerian-Le Goff L, Salin P, Savasta M, Sgambato-Faure V.
Eur J Neurosci. 2010 Aug;32(3):423-34. PMID: 20673310

PUBLICATION

Deep brain stimulation of the center median-parafascicular complex of the thalamus has efficient anti-parkinsonian action associated with widespread cellular responses in the basal ganglia network in a rat model of Parkinson's disease.

Jouve L, Salin P, Melon C, Kerkerian-Le Goff L.
J Neurosci. 2010 Jul 21;30(29):9919-28. PMID: 20660274

PUBLICATION

[Acetylcholinesterase inhibitors in Alzheimer's disease: further comments on their mechanisms of action and therapeutic consequences].

Nieoullon A.
Psychol Neuropsychiatr Vieil. 2010 Jun;8(2):123-31. [Article in French] PMID: 20525543

PUBLICATION

Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury.

Cornille E, Abou-Hamdan M, Khrestchatisky M, Nieoullon A, de Reggi M, Gharib B.
BMC Neurosci. 2010 Apr 23;11:51 PMID: 20416081

PUBLICATION

Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

Beurrier C, Faideau M, Bennouar KE, Escartin C, Kerkerian-Le Goff L, Bonvento G, Gubellini P.
PLoS One. 2010 Jan 1;5(1):e8550. PMID: 20062544

PUBLICATION

Downstream mechanisms triggered by mitochondrial dysfunction in the basal ganglia: from experimental models to neurodegenerative diseases.

Gubellini P, Picconi B, Di Filippo M, Calabresi P.
Biochim Biophys Acta. 2010 Jan;1802(1):151-61. PMID: 1968356

PUBLICATION

Effects of GPi and STN inactivation on physiological, motor, cognitive and motivational processes in animal models of Parkinson's disease.

Baunez C, Gubellini P.
Prog Brain Res. 2010;183:235-58. PMID: 20696323

PUBLICATION

Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson's disease.

Goff LK, Jouve L, Melon C, Salin P.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S167-70. PMID: 20082982

PUBLICATION

Cocaine-induced stereotypy is linked to an imbalance between the medial prefrontal and sensorimotor circuits of the basal ganglia.

Aliane V, Pérez S, Nieoullon A, Deniau JM, Kemel ML.
Eur J Neurosci. 2009 Oct;30(7):1269-79. PMID: 19769590

PUBLICATION

Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism.

Beurrier C, Lopez S, Révy D, Selvam C, Goudet C, Lhérondel M, Gubellini P, Kerkerian-LeGoff L, Acher F, Pin JP, Amalric M.
FASEB J. 2009 Oct;23(10):3619-28. PMID: 19525404

PUBLICATION

Mechanisms contributing to the phase-dependent regulation of neurogenesis by the novel antidepressant, agomelatine, in the adult rat hippocampus.

Soumier A, Banasr M, Lortet S, Masmejean F, Bernard N, Kerkerian-Le-Goff L, Gabriel C, Millan MJ, Mocaer E, Daszuta A.
Neuropsychopharmacology. 2009 Oct;34(11):2390-403. PMID: 19571795

PUBLICATION

Different functional basal ganglia subcircuits associated with anti-akinetic and dyskinesiogenic effects of antiparkinsonian therapies.

Lacombe E, Khaindrava V, Melon C, Oueslati A, Kerkerian-Le Goff L, Salin P.
Neurobiol Dis. 2009 Oct;36(1):116-25. PMID: 19615446

PUBLICATION

Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.

Gubellini P, Salin P, Kerkerian-Le Goff L, Baunez C.
Prog Neurobiol. 2009 Sep;89(1):79-123. PMID: 19559747

PUBLICATION

Changes to interneuron-driven striatal microcircuits in a rat model of Parkinson's disease.

Salin P, López IP, Kachidian P, Barroso-Chinea P, Rico AJ, Gómez-Bautista V, Coulon P, Kerkerian-Le Goff L, Lanciego JL.
Neurobiol Dis. 2009 Jun;34(3):545-52. PMID: 19341798

PUBLICATION

Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson's disease treatment.

Cuomo D, Martella G, Barabino E, Platania P, Vita D, Madeo G, Selvam C, Goudet C, Oueslati N, Pin JP, Acher F, Pisani A, Beurrier C, Melon C, Kerkerian-Le Goff L, Gubellini P.
J Neurochem. 2009 May;109(4):1096-105. PMID: 19519781

PUBLICATION

Role of glutamate transporters in corticostriatal synaptic transmission.

Beurrier C, Bonvento G, Kerkerian-Le Goff L, Gubellini P.
Neuroscience. 2009 Feb 18;158(4):1608-15. PMID: 19063944

PUBLICATION

Impact of surgery targeting the caudal intralaminar thalamic nuclei on the pathophysiological functioning of basal ganglia in a rat model of Parkinson's disease.

Kerkerian-Le Goff L, Bacci JJ, Jouve L, Melon C, Salin P.
Brain Res Bull. 2009 Feb 16;78(2-3):80-4. PMID: 18790021

PUBLICATION

Importance of circadian rhythmicity in the cholinergic treatment of Alzheimer's disease: focus on galantamine*.

Nieoullon A, Bentué-Ferrer D, Bordet R, Tsolaki M, Förstl H.
Curr Med Res Opin. 2008 Dec;24(12):3357-67. PMID: 19032118

PUBLICATION

High-resolution neuroanatomical tract-tracing for the analysis of striatal microcircuits.

Salin P, Castle M, Kachidian P, Barroso-Chinea P, López IP, Rico AJ, Kerkerian-Le Goff L, Coulon P, Lanciego JL.
Brain Res. 2008 Jul 24;1221:49-58. PMID: 18561898

PUBLICATION

Plasma membrane expression of the neuronal glutamate transporter EAAC1 is regulated by glial factors: evidence for different regulatory pathways associated with neuronal maturation.

Lortet S, Canolle B, Masmejean F, Nieoullon A.
Neurochem Int. 2008 Jun;52(7):1373-82. PMID: 18400334

PUBLICATION

Preferential vulnerability of mesencephalic dopamine neurons to glutamate transporter dysfunction.

Nafia I, Re DB, Masmejean F, Melon C, Kachidian P, Kerkerian-Le Goff L, Nieoullon A, Had-Aissouni L.
J Neurochem. 2008 Apr;105(2):484-96. PMID: 18042178

PUBLICATION

Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system.

Sage D, Salin P, Alcaraz G, Castets F, Giraud P, Crest M, Mazet B, Clerc N.
J Comp Neurol. 2007 Oct 1;504(4):363-78. PMID: 17663442

PUBLICATION

High-frequency stimulation of the subthalamic nucleus potentiates L-DOPA-induced neurochemical changes in the striatum in a rat model of Parkinson's disease.

Oueslati A, Sgambato-Faure V, Melon C, Kachidian P, Gubellini P, Amri M,Kerkerian-Le Goff L, Salin P.
J Neurosci. 2007 Feb 28;27(9):2377-86. PMID: 17329435

PUBLICATION

Deficits of glutamate transmission in the striatum of experimental hemiballism.

Centonze D, Rossi S, Gubellini P, De Chiara V, Tscherter A, Prosperetti C, Picconi B, Bernardi G, Calabresi P, Baunez C.
Neuroscience. 2006 Nov 17;143(1):213-21. PMID: 16938405

PUBLICATION

Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA treatment in experimental parkinsonism: effects on motor behaviour and striatal glutamate transmission.

Gubellini P, Eusebio A, Oueslati A, Melon C, Kerkerian-Le Goff L, Salin P.
Eur J Neurosci. 2006 Sep;24(6):1802-14. PMID: 17004943

PUBLICATION

The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?

Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S.
J Neurochem. 2006 Aug;98(4):1007-18. PMID: 16800850

PUBLICATION

Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport.

Re DB, Nafia I, Melon C, Shimamoto K, Kerkerian-Le Goff L, Had-Aissouni L.
Glia. 2006 Jul;54(1):47-57. PMID: 16673373

PUBLICATION

Ciliary neurotrophic factor activates astrocytes, redistributes their glutamate transporters GLAST and GLT-1 to raft microdomains, and improves glutamate handling in vivo.

Escartin C, Brouillet E, Gubellini P, Trioulier Y, Jacquard C, Smadja C, Knott GW,Kerkerian-Le Goff L, Déglon N, Hantraye P, Bonvento G.
J Neurosci. 2006 May 31;26(22):5978-89. PMID: 16738240

PUBLICATION

Transient hippocampal down-regulation of Kv1.1 subunit mRNA during associative learning in rats.

Kourrich S, Manrique C, Salin P, Mourre C.
Learn Mem. 2005 Sep-Oct;12(5):511-9. PMID: 16204203

PUBLICATION

Enhanced delivery of gamma-secretase inhibitor DAPT into the brain via an ascorbic acid mediated strategy.

Quéléver G, Kachidian P, Melon C, Garino C, Laras Y, Pietrancosta N, Sheha M, Louis Kraus J.
Org Biomol Chem. 2005 Jul 7;3(13):2450-7. PMID: 15976862

PUBLICATION

Glial soluble factors regulate the activity and expression of the neuronal glutamate transporter EAAC1: implication of cholesterol.

Canolle B, Masmejean F, Melon C, Nieoullon A, Pisano P, Lortet S.
J Neurochem. 2004 Mar;88(6):1521-32. PMID: 15009653

PUBLICATION

Metabotropic glutamate 5 receptor blockade alleviates akinesia by normalizing activity of selective basal-ganglia structures in parkinsonian rats.

Breysse N, Amalric M, Salin P.
J Neurosci. 2003 Sep 10;23(23):8302-9. PMID: 12967992

INPI n° 2942412 : Microstimulateur cerebral d’accessibilité aisée et méthode d’installation d’un tel microstimulateur (co-inventors: P. Salin, C. Forni, O. Mainard, C. Melon, E. Richard, and D. Goguenheim) CNRS Patent.

Interactions

IBDM
NATIONAL
  • Olga Corti, ICM, Paris
  • Alice Carrier, CRCM, Marseille
  • Abdel Ouaggazal et Marianne Amalric, LNC Marseille
  • Franck Durif, CHU de Clermont-Ferrand
  • Eduardo Gascon, INT Marseille
  • ConnectoVir platform, INT Marseille
INTERNATIONAL
  • José-Luis Lanciego, Center for Applied Medical Research (CIMA), University of Navarra, Spain

Members more

Corinne Beurrier Paolo Gubellini   Philippe Kachidian Jean-pierre Kessler Gwenaëlle Laverne Sylviane Lortet Nicolas Maurice Christophe Melon Jordan Molitor André Nieoullon Thomas Rival Amandine Ruiz Pascal Salin Olena Varuk
Lydia Kerkerian - Le Goff
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Lydia Kerkerian - Le Goff

Researcher

Corinne Beurrier
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Corinne Beurrier

Researcher

Paolo Gubellini
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Paolo Gubellini

Researcher

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Salimata diagne Houndjo

Visiting Scientist

Philippe Kachidian
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Philippe Kachidian

University lecturer

Jean-pierre Kessler
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Jean-pierre Kessler

Researcher

Gwenaëlle Laverne
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Gwenaëlle Laverne

Technical staff

Sylviane Lortet
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Sylviane Lortet

University lecturer

Nicolas Maurice
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Nicolas Maurice

Researcher

Christophe Melon
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Christophe Melon

Technical staff

Jordan Molitor
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Jordan Molitor

PhD student

André Nieoullon
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André Nieoullon

Emeritat

Thomas Rival
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Thomas Rival

University lecturer

Thomas, University lecturer, joined the team on September 2007. In addition to his teaching responsibilities at the Bachelor and Master levels, Thomas has recently decided to use the power of Drosophila genetic to decipher the molecular mechanisms that control mitochondria dynamics in vivo. He has developed tools that allow him to visualize mitochondria fusion and fission events in vivo and to identify the proteins that regulate this process.

Amandine Ruiz
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Amandine Ruiz

Others

Pascal Salin
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Pascal Salin

Researcher

Olena Varuk
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Olena Varuk

PhD student

Alumni

  • Maxime AssousCenter for Molecular and Behavioral Neuroscience, Rutger University, Newark, NJ, USA
  • Dorian Chabbert, Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA
  • Maroua Hanini-Daoud, Groupe de recherche sur le système nerveux central (GRSNC), Département de Neurosciences de l’université de Montréal, Canada
  • Abid OueslatiMolecular and Cellular Neurodegeneration Laboratory, CHU Research Center, Quebec City, Canada
  • Delphine RevySyncrosome, Marseille, France
  • Sandra RobeletSyncrosome, Marseille, France
  • Diane B RéDepartment of Environmental Health Sciences, Columbia University, New York, NY, USA.

Overview

Model organisms
Biological process studied
  • Synaptic transmission
  • Mitochondrial dynamics
  • Neurodegeneration
  • Neuroplasticity
Biological techniques
  • Behavioral tests
  • Molecular and cellular biology
  • Electrophysiology (in vivo and ex-vivo)
  • Optogenetics
  • Stereotactic surgery
  • Quantitative histological approaches (immunocytochemistry, in situ hybridization)
  • Confocal and electron microscopic imaging
Medical application
  • Basal Ganglia-related pathologies (Parkinson’s disease, Huntington’s disease, Autism Spectrum Disorder….)
  • Alzheimer’s disease
  • Charcot-Marie-Tooth disease