Oligodendrocytes: a key metabolic support for energy-voracious parvalbumin neurons?

GABA-releasing parvalbumin-expressing interneurons (PV-IN) are key orchestrators of the cortex and the hippocampus. A dysfunction of PV-INs, plays a causal role in phenotypes relevant to -Brain-affecting diseases- epilepsy, autism, and schizophrenia. Despite being a minority cell type in the hippocampus, PV-INs exert a powerful inhibition and finely synchronize the neuronal circuits. PV-IN locally innervate a large number of target neurons near the site of action potential initiation (each PV-IN contacts up to 2000 pyramidal neurons of the hippocampus) and tune the population activity. To sustain their unique properties, PV-IN are highly energy-voracious, particularly during metabolically costly oscillations.
A growing piece of evidence showed that hippocampal PV-IN axons are encapsulated by a myelin sheath and represents most of the myelin content in the hippocampus. Formed by the oligodendrocytes, myelin appears instrumental for the PV-IN’s electrophysiological properties, and the regulation of behavior-related oscillations in vivo. Oligodendrocyte-neuron coupling via myelination could also provide the metabolic support requested by the energy-demanding PV-INs. Oligodendrocyte supply lactate, a metabolite crucial for long-term axonal integrity, through the transporters of lactate MCT1.
Importantly, the specific reduction of MCT1 in the hippocampus, using RNA interference, caused long-term memory deficits. However, the specific impact of MCT1 on PV-IN properties has not been explored to date.
This intership objective will be to investigate how MCT1 regulates PV-IN physiological properties and myelination as well as hippocampal function, through the following specific aims:
Specific aim 1: Testing the effect of MCT1 inhibition/downregulation on PV-IN discharge and hippocampal network activity.
Specific aim 2: Testing the effect of MCT1 inhibition/downregulation on PV-IN myelination, as well as on PV-IN and Oligodendrocyte integrity and survival.
The manipulation of MCT1 (Aims 1-2) will be performed either using a selective inhibitor or via the conditional genetic depletion of MCT1 in hippocampal oligodendrocytes (using an AAV-MBP-cre and MCT1-floxed mice). Aims 1 and 2 will be performed in vitro using organotypic hippocampal cultures and calcium imaging, following by immunohistochemistry.
This internship will allow you to familiarize yourself with many techniques:
– Hippocampal organotypic culture
– Drug and AAV viral vector-based cell specific knock-down
– Calcium imaging using 2-photons microscopes
– Immunohistochemistry and confocal imaging
– Data analysis

We (Nathalie Bernard and Thomas Marissal) are looking for motivated, persevering, curious students who appreciate teamwork and who have a basic training in neuroscience and/or cell biology. Interested students should feel comfortable with the experiments on mice which will be carried out, of course, in strict compliance with ethical rules and animal welfare and in the presence of the supervisor.
In addition, we would like to welcome students wishing to pursue a PhD, and whose file shows a real potential to obtain a PhD grant via either the competition of the doctoral school 62, or the international cotutelle competition organized by NeuroSchool.
In return, we (the supervisors) guarantee the students a supportive and stimulating translational research environment, which will put them in the best possible position to progress rapidly, to learn many techniques of imaging, neurobiology, cell biology, genetics, and, if necessary, to obtain thesis funding.

This project will be a collaborative project led by two labs in two campus : the Luminy campus at INMED (70%) and the Timone campus at MMG (30%).
Organotypic cultures and calcium imaging will be performed on the supervision of Dr. Thomas Marissal at INMED, Luminy. Thomas Marissal (TM) is principal investigator (“chargé de recherche”) at the Mediterranean Institute of Neurobiology (Inmed) in the Neuronal coding and plasticity in epilepsy team. He is specialized in interneuron physiopathology, calcium imaging and mouse behavior.
Immunohistochemistry, confocal imaging and myelination analysis will be performed under the supervision of Dr. Nathalie Bernard-Marissal at MMG, Timone.
Nathalie Bernard (NBM) is chargée de recherche (INSERM) at the Marseille Medical Genetics (MMG) in the Translational Neuromyology team. She is specialized in neuronal metabolism, neuronal-glial interaction as well as molecular biology and AAV vector design.