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

Keywords

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

Publications

Veyrac A.*, Gros A.*, Bruel-Jungerman E., Rochefort C., Kleine Borgmann F.B., Jessberger S., Laroche S. (2013) Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning. Proc. Natl. Acad. Sci. USA, 110:7062-7067.

Besnard A., Caboche J., Laroche S. (2013) Comparative dynamics of MAPK/ERK signaling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval. Brain Struc. Function, [Epub ahead of print].

Morice E.*, Farley S.*, Poirier R.*, Dallerac G., Chagneau C., Pannetier S., Hanauer A., Davis S., Vaillend C., Laroche S. (2013) Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome. Neurobiol. Disease, 58:156-168.

Penke Z., Morice E., Veyrac A., Gros A., Chagneau C., Le Blanc P., Samson N., Baumgärtel K., Mansuy I.M., Davis S., Laroche S. (2013) Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory. Phil. Trans.R. Soc. B, in press.

Perronnet C., Chagneau C., Le Blanc P., Samson-Desvignes N., Mornet D., Laroche S., De La Porte S., Vaillend C. (2012) Upregulation of brain utrophin does not rescue behavioral alterations in dystrophin-deficient mice. Human Molecular Genetics,21:2263-2276.

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.

Team members

VAILLEND Cyrille
POIRIER Roselyne
DAVIS Sabrina
ENDERLIN Valérie
VEYRAC Alexandra
GROS Alexandra
LUNION Steeve
CHAUSSENOT Rémi
CHAALAL Amina

Lab rotation

Thyroid dysfunction and Alzheimer’s disease

Team leader: 

LAROCHE Serge

Dates: 

January 2, 2018 - June 29, 2018

Application deadline: 

June 29, 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

Supervisor: 

ENDERLIN Valérie