Internship

Search for new functions of oligodendrocyte progenitor cells: from behavior to electrophysiology

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The objective of this project is to get insight into unknown functions of oligodendrocyte precursor cells (OPC) in the adult brain. We will characterize a new mouse line generated in the lab in which OPC can be thoroughly killed in a very specific and time-controlled manner. These mice will be submitted to a battery of behavioral tests and then sacrificed for histological and electrophysiological analyses (patch clamp on hippocampal slices).
This study will hopefully help understanding if and how OPC modulate brain function.

Description

A population of quiescent progenitors, the oligodendrocyte precursor cells (OPC) is disseminated throughout the adult brain parenchyma and represent around 5-10% of all neural cells. OPC can respond to environmental stimuli and differentiate into mature myelinating oligodendrocytes. There are thus involved in physiological and post-lesional neuroplasticity. Recent studies revealed how neuronal activity can trigger OPC differentiation and modulate myelination pattern, leading to the development of the concept of “adaptive myelination”. Yet very little is known about a potential role of OPC themselves, independently of producing oligodendrocytes. We hypothesize that if OPC can respond to neuronal signals, they may also be able to modulate neuronal excitability and thus contribute to brain homeostasis. In this project, we will take advantage of a new mouse line that we generated in our lab, in which we can specifically kill OPC in a timely controlled manner. We will characterize these mice lacking OPC at behavioral and electrophysiological levels.
Mice will be submitted to a variety of behavioral tests to assess anxiety and exploratory behaviors (Elevated-plus maze, Open field test), and more complex cognitive functions (Y-maze alternation, object location, virtual 3D orientation tests). After the behavioral tests, half of the mice will be sacrificed for histological analyses to check for OPC ablation in the different brain structures, and more specifically in hippocampus, and the other half will be dedicated to electrophysiological studies.
Electrophysiological analyses will be performed in vitro in hippocampal slices. The impact of the OPC ablation will be tested on dentate granule cells in the hippocampus. Patch-clamp recordings will allow us to compare both the intrinsic and synaptic neuronal properties; we will assess the resting membrane potential, the input resistance, the spike threshold, the firing pattern, the action potential waveform, the excitatory/inhibitory balance, and the NMDA/AMPA receptor-mediated EPSC.
The student in charge of this study will be co-directed by Myriam Cayre (IBDM- mice production, behavioral tests) and Valérie Crépel (INMED- electrophysiology).

Desired profile

The student should be familiar with animal handling, in order to have unstressed mice for behavioral testing. Beside, electrophysiology and patch-clamp experiments require meticulousness, and precision. Finally, we are looking for a student highly motivated by science and dedicated to his work.

Host institution

The project will be conducted in two laboratories both located on the Luminy campus: Institute for Developmental Biology of Marseille (IBDM) and Mediterranean Institute of Neurobiology (INMED).
In IBDM, the host team “Stem cells and brain repair” is directed by Pascale Durbec. The main research expertise of the team is myelin biology and myelin repair.
At INMED, the host team “Neuronal coding and plasticity in epilepsy” is directed by Valérie Crépel. The research focus is on neuronal computation and plasticity in normal and pathological conditions.

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