Cellular and molecular mechanisms of plasticity and memory

Leader

Co-Leaders

Research center

Bâtiment 145, Centre d'études de Saclay
91191 Gif sur Yvette
Philippe Vernier

Institution

CNRS
Université Paris Sud 11
ED 568 BioSigNe
Université Paris Sud 11

Laboratory

Département Cognition & Comportements
UMR9197
Idex NeuroSaclay, contrat ANR

Mots clefs

Synaptic plasticity
Learning and Memory
Adult hippocampal neurogenesis
Intellectual deficiencies
Alzheimer's disease
 

publications

Chaalal A, Poirier R, Blum D, Gillet B, Le Blanc P, Basquin M, Buée L, Laroche S, Enderlin E. (2014) PTU-induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer’s disease in the hippocampus and spatial memory impairments. Hippocampus, 24(11) : 1381-1393.

Vaillend C, Chaussenot R. (2017) Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice. Hum Mol Genet, 26(6):1041-1055.

Maglorius Renkilaraj MR, Baudouin L, Wells CM, Doulazmi M, Wehrlé R, Cannaya V, Bachelin C, Barnier JV, Jia Z, Nait Oumesmar B, Dusart I, Bouslama-Oueghlani L (2017) The intellectual disability protein PAK3 regulates oligodendrocyte precursor cell differentiation. Neurobiol Dis ; 98:137-148.

Guillot F, Kemppainen S, Lavasseur G, Miettinen PO, Laroche S, Tanila H, Davis S (2016) Brain-Specific Basal and Novelty-Induced Alternations in PI3K-Akt and MAPK/ERK Signaling in a Middle-Aged AβPP/PS1 Mouse Model of Alzheimer’s Disease. J Alzheimers Dis.51(4):1157-1173.

Goyenvalle A, Griffith G, Babbs A, El Andaloussi S, Ezzat K, Avril A, Dugovic B, Chaussenot R, Ferry A, Voit T, Amthor H, Bühr C, Schürch S, Wood MJ, Davies KE, Vaillend C, Leumann C, Garcia L. (2015) Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nat Med. 21(3):270-5.

 

Fields of research

Neurophysiology / systems neuroscience

Research Theme

Research in the team focuses on the cellular and molecular mechanisms of learning and memory and on identifying mechanisms responsible for memory dysfunction in brain pathologies. Our objective is to identify in different structures of the brain such as the hippocampus and cortex the cellular and molecular mechanisms underlying brain of plasticity, to characterize their role in the formation of memories and identify networks and brain structures within which these changes occur during the laying down of memories. Our approach, from genes to function, leads to both the identification of cellular and synaptic changes linked to learning and to the functional characterisation of the role of signalling cascades, transcription factors, and the regulation of genes and proteins underlying different phases of plasticity and forms of memory. The research projects cover different facets of plasticity and memory, ranging from synaptic mechanisms to neurogenesis, complemented by the analysis of the cellular and molecular mechanisms of memory dysfunction associated with pathologies of genetic origin such as mental retardation or neurodegenerative diseases such as Alzheimer's disease. In these animal models, we explore the potential of genetic, pharmacological or behavioural therapies. The research is based on multidisciplinary approaches including cellular and molecular biology, biochemistry, functional neuroanatomy and imaging, pharmacology, in vivo electrophysiology and behavioural analyses of learning and memory in rats and genetically modified mice.

Membres de l'équipe

Sabrina Davis,Jean-Vianney Barnier, Valérie Enderlin, Roseline Poirier, Sandrine Guyon, Véronique Rousseau, Ophélie Vacca, Charlotte Castillon, Mehdi Belmaati, Kevin Duarte, Faouzi Zarrouki

Lab rotation

Thyroid dysfunction and Alzheimer’s disease

Chercheur responsable: 

LAROCHE Serge

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018

~ April-June 2018


Project

Factors impacting the risk of developing sporadic forms of Alzheimer’s disease (AD), which accounts for over 99% of the cases, remain poorly understood. Thyroid dysfunction is a risk factor for Alzheimer’s disease (AD) [Davis et al, 2008 Curr Aging Sci 1:175–81]. We showed that hypothyroidism in rats leads to early brain changes reminiscent of AD, notably hippocampal A and proinflammatory cytokine production, Tau phosphorylation associated with memory deficits [Ghenimi et al, 2010 J Neuroendocrinol 22:951; Chaalal et al, 2014 Hippocampus 24:1381]. Our recent findings indicate that thyroid hormone (TH) supplementation rescues most of these alterations. Our general objective is now to achieve new insights into the relationships between localized hypothyroidism and AD-related pathological hallmarks.Recent evidence suggests a detrimental impact of hypothyroidism on (1) synaptic transmission and memory, (2) neuronal and astrocytes survival [Cortes et al, 2012 Thyroid 22:9]. TH is also considered as an important signaling factor that affects glial changes [Noda, 2015 Front Cell Neurosci  9:194]. Changes of microglia and astrocytes functions may contribute to the early inflammatory response and modulate the level of Aβ peptide and Tau phosphorylation [Morales et al, 2015 Front Cell Neurosci 8:112]. The project will be directed at characterizing the inflammatory response and determining its potential role in the sequence of events that leads to a favorable environment for the development of AD pathology under conditions of hypothyroidism. 

Contact

Neuro PSI - Université Paris Sud 91405 Orsay - +33 1 69 15 49 88 - valerie.enderlin@u-psud.fr

Superviseur: 

ENDERLIN Valérie