Michaël RUSSIER

Associate professor, AMU

Position and past experience

2012 – 2025 Associate professor at INSERM – Aix-Marseille université (UNIS – U1072)

2003 – 2011 Associate professor at CNRS – Université d’Aix-Marseille I (LNIA – UMR 6149)

2001 – 2003 Postdoc at INSERM U464

2001: PhD in Neursciences (CNRS UPR 9041/Université Aix-Marseille III)

Field of research:

Synaptic plasticity, plasticity of intrinsic neuronal excitability (LTP-IE), axon physiology, cellular mechanisms underlying amblyopia and epilepsy

Methods:

Patch-clamp electrophysiology, live imaging of neurons, pharmacology in acute slices and organotypic slice cultures of brain explants, immunohistochemistry.

Current research interest

Cholesterol regulation of ion channel function and plasticity: a new mechanism in amblyopia
Amblyopia is a visual deficit resulting from abnormal visual experience during postnatal development caused by strabismus, congenital cataract, anisometropia (an important difference in refractive error between the two eyes), or ptosis (partial or complete drop of the superior eyelid). In the adult, amblyopia is characterized by the irreversible loss of visual acuity that cannot be compensated by optical means. Amblyopia affects 2-5% of the population. The treatment of amblyopia is possible only during the first 6-7 years of life with the treatment of the cause of abnormal vision (removal of the strabismus, removal of the cataract, correction of refractive error, etc…) and reversed occlusion. When this sensitive period is exceeded, the visual deficit is irreversible.

Monocular deprivation (MD), an animal model of amblyopia, has two major consequences: i) strong reduction in visually evoked potentials in the cortex and ii) loss of binocular activation of visual cortical neurons. We have recently shown that MD reduces the intrinsic responsiveness of dorsal lateral geniculate nucleus (dLGN) neurons. In addition, we showed that stimulation of afferent retinal inputs spiking induces long-term potentiation of intrinsic neuronal excitability (LTP-IE) in dLGN relay neurons. LTP-IE is mediated by a calcium entry through Cav1.1 channels and involves the downregulation of Kv1.1 channels.

Plasma membranes of neurons are composed of a wide variety of lipids and highly specialized microdomains called lipid rafts that concentrate membrane proteins such as membrane receptors and ion channels. Among lipids, gangliosides and cholesterol, the main lipid compounds of lipid rafts in neurons, are known for directly interacting with membrane proteins via conserved consensus domains. The role of lipids in the regulation of voltage-gated ion channels involved in the control of intrinsic excitability has recently received increasing attention. Lipids such as ganglioside GM1 or valproic acid have been shown to reduce visual deficits in experimental amblyopia but no mechanistic link has been established between lipids and cellular mechanism involved in the visual recovery.
Our objective is to decipher the molecular mechanisms linking cholesterol and Cav1.1 and Kv1.1, to determine whether change in cholesterol interaction with Cav1.1 and Kv1.1 reverberates on LTP-IE in dLGN.

Microglia and neuronal excitability
Microglia (MG) represent the major population of immune cells of the brain and have many important functions. They are classically involved in the clearance of cellular debris and inactive synapses during development, after learning or following injury. However, MG are also essential in the formation of new excitatory synapses and in the stabilization of inhibitory synapses. In the mature brain, MG are essentially in 2 distinct states: a homeostatic state (MG sense their surroundings) or a reactive state (MG change shape, gene expression and instruct other cells by releasing inflammatory cytokines). MG occupy therefore a key position in neuroinflammatory and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.Microglial processes contact different neuronal comparments, including synapses, somata and the axon initial segment (AIS). While the nature and functional consequences of contacts between MG and synapses and soma have been the subject of numerous studies, MG-AIS interactions have been little studied. We are currently filling this gap.