Hélène Marie, PhD

Hélène Marie, PhD

Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

Dr Hélène Marie’s team is interested in understanding how physiological and pathological conditions shape neuronal plasticity. We have an integrated approach to delineate how molecular changes translate into behavioural outcomes. We have strong expertise in in vitro electrophysiology on brain slices (field and patch clamp recordings) and in behaviour. We use viral approaches for in vivo protein expression as well as transgenic lines to alter brain molecular mechanisms. We are also currently developing pharmacogenetic and optogenetic approaches to address our questions.

Our research focuses on 3 main axis:

1. Alzheimer's disease (AD)

AD is the most frequent neurodegenerative disorder. Chronic stress is known to be a key risk factor in the development of the pathology. We therefore seek to understand how stress and dysregulation of the corticotrope axis contributes to the onset of AD-related synaptic alterations and how these modifications translate into impaired mnemonic functions. Also, neuropathologically, AD is characterized by progressive appearance of oligomers of Amyloid beta (Aβ) peptide and plaques. Since increased Aβ load per se cannot fully account for the deficits observed in AD, we explore the functional role of other peptides produced by Amyloid precursor protein (APP) processing.

2. Epilepsy

Epilepsy is a devastating neurological disorder, which can impair brain function. In collaboration with the team of Dr. Mantegazza (IPMC), we seek to understand how synaptic function and memory are perturbed in mouse models of this disorder.

3. Social stress

When overwhelming, stress increases the morbidity for psychiatric disorders such as major depression and inability to socially perform. These aberrant behaviours are reproduced in mice repetitively exposed to social defeat stress. This results in a persistent boost of dopamine (DA) transmission. This project aims at identifying the inputs that shape DA responsiveness in response to social stress. This may form the pathophysiological basis for major psychiatric disorders.

In collaboration with computational neuroscientists, we are also interested in modelling disease-related synaptic alterations to understand how these impact the function of hippocampal neurons at the single cell level and at the network level.

Key Publications:
Pousinha PA, Mouska X, Bianchi D, Temido-Ferreira M, Rajão-Saraiva J, Gomes R, Fernandez SP, Salgueiro-Pereira AR, Gandin C, Raymond EF, Barik J, Goutagny R, Bethus I, Lopes LV, Migliore M, Marie H. The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding. Cell Rep. 2019 Oct 8;29(2):317-331.e5. doi: 10.1016/j.celrep.2019.08.103.

Kootar S, Frandemiche ML, Dhib G, Mouska X, Lorivel T, Poupon-Silvestre G, Hunt H, Tronche F, Bethus I, Barik J, Marie H. Identification of an acute functional cross-talk between amyloid-β and glucocorticoid receptors at hippocampal excitatory synapses. Neurobiol Dis. 2018;118:117-128.

Temido-Ferreira M, Ferreira DG, Batalha VL, Marques-Morgado I, Coelho JE, Pereira P, Gomes R, Pinto A, Carvalho S, Canas PM, Cuvelier L, Buée-Scherrer V, Faivre E, Baqi Y, Müller CE, Pimentel J, Schiffmann SN, Buée L, Bader M, Outeiro TF, Blum D, Cunha RA, Marie H, Pousinha PA, Lopes LV. Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors. Molecular Psychiatry. 2018;doi:10.1038/s41380-018-0110-9.

Pousinha PA, Mouska X, Raymond EF, Gwizdek C, Dhib G, Poupon G, Zaragosi LE, Giudici C, Bethus I, Pacary E, Willem M, Marie H. Physiological and pathophysiological control of synaptic GluN2B−NMDA receptors by the C−terminal domain of amyloid precursor protein. Elife. 2017;6:1–29.

Willem M, Tahirovic S, Busche MA, Ovsepian SV, Chafai M, Kootar S, Hornburg D, Evans LDB, Moore S, Daria A, Hampel H, Müller V, Giudici C, Nuscher B, Wenninger-Weinzierl A, Kremmer E, Heneka MT, Thal DR, Giedraitis V, Lannfelt L, Müller U, Livesey FJ, Meissner F, Herms J, Konnerth A, Marie H, Haass C. Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature. 2015; 526(7573):443-7.

Lanté F, Chafai M, Raymond EF, Salgueiro Pereira AR, Mouska X, Kootar S, Barik J, Bethus I, Marie H. Subchronic glucocorticoid receptor inhibition rescues early episodic memory and synaptic plasticity deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology. 2015;40:1772-81.

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