Job ID: 118109
PhD project: Oligodendrocytes: a key metabolic support for energy-voracious parvalbumin neurons?
Position: Ph.D. Student
Deadline: 14 April 2024
Employment Start Date: 10 October 2024
Contract Length: 3 years
City: Marseille
Country: France
Institution: Aix-Marseille Université
Department: MMG, INMED
Description:
The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master’s degree in a non-French university. This project is one of the 13 proposed projects. Not all proposed projects will be funded, check our website for details.
State of the art: Key orchestrators of the hippocampal network activity and related behaviors, Parvalbumin-expressing interneurons (PV-INs) innervate a large number of target neurons and discharge at high frequency and action potentials propagate along their myelinated axon with high speed and reliability. To maintain their unique properties, PV-INs are energy-intensive, particularly during metabolically costly oscillations. We believe that oligodendrocytes (OLs) could maintain PV-IN properties and more broadly hippocampal function, not only through myelination, but also by providing a critical relay energy source in the form of lactate via the transporters MCT1/MCT2 under pathological conditions or at high energy expenditure. MCT1 enables the transfer of lactate both into OLs and into the extracellular space, from where lactate is then imported by MCT2 into the neuron. Importantly, deletion of one of these transporters affects hippocampal-related learning and memory processes. However, it was not investigated whether these observations specifically implicate PV-IN dysfunction.
Objectives: The main project objective will be to determine whether the coupling between OL and PV-IN through the lactate transporters MCT1 and MCT2 is key to PV-IN properties and hippocampal functions. Specific aims will be to test whether MCT1 and MCT2 impact: (1) PV-IN discharge and hippocampal network activity, (2) PV-IN myelination, as well as PV-IN and OL integrity? (3) hippocampal-dependent learning and memory function.
Methods: We will use a combination of cellular biology, immunohistochemistry, confocal and two-photon microscopy and behavioral testing in conditions where MCT1 or MCT2 are genetically or pharmacologically manipulated, using wild-type mice or models related to neuro-psychiatric diseases associated with PV-IN dysfunction.
Expected results: We believe this project will not only bring new insights about the mechanisms supporting the energetically costly role of PV-IN especially during the metabolically voracious processes of learning and memory, but also provide insightful information regarding their vulnerability to many genetic or environmental stressors in the context of neuropsychiatric pathologies.
Feasibility: All the necessary equipment and tools (e.g., biosafety level 2 room, behavioral and imaging facility, surgical room, drugs, vectors) are available, and techniques are routinely used in either of the two labs.
Complementary between the 2 labs: This project will be supervised by 2 complementary PI (N. Bernard-Marissal, NBM, and T. Marissal, TM) in 2 labs in Marseille (MMG and INMED). NBM is expert in neuronal metabolism, neuronal-glial interaction as well as molecular biology and AAV vector design and will bring the genetic tools necessary for each project parts and supervise experiments related to aims 1 and 2. TM is expert in interneuron physiopathology, Ca2+ imaging and mouse behavior, he will supervise the experiments related to the aims 1 and 3.
Expected candidate profile: We are looking for a motivated, persevering, curious, team worker candidate. He/she must have basic knowledge in neuroscience and/or cell biology. Habilitation to work with mice as well as experience in cell culture and 2-photon imaging would be a plus.