The role of PV+ basket cell axon myelination in temporal synchrony of the hippocampal CA2 network

Description du projet

Comprendre le rôle de la myélinisation des axones au sein de l’hippocampe

Le stockage et la récupération de souvenirs a lieu dans l’hippocampe, la partie du cerveau responsable de l’apprentissage et de la mémoire. Dans la mesure où ces processus dépendent de la transmission précise de l’information, le projet MyeSync, financé par l’UE, s’intéresse au rôle de la myélinisation des axones dans la consolidation de la mémoire et la performance cognitive. La myélinisation des axones implique le repliement des axones neuronaux avec de la myéline, qui les isole et leur permet de transmettre rapidement des impulsions électriques. Les chercheurs entreprendront une approche pluridisciplinaire pour étudier comment des changements biophysiques dans les petits compartiments neuronaux sont susceptibles d’altérer les réseaux neuronaux, puis, en définitive, de dicter leur comportement.

Objectif

The hippocampus located in the temporal lobe of the brain is of fundamental importance for storage and retrieval of episodic memories. Such brain computations take place at a time scale of milliseconds or less, and rely on neuronal information transfer over subcellular structures which are called axons. Neuronal precision and speed can be achieved by wrapping axons with multi-lamellar membrane sheets of myelin and is of critical importance for proper brain function. Until recently, myelination was thought to be exclusive to long-range excitatory neuronal projections. This view has been drastically revised, and it is now commonly accepted that myelination can be abundant around the axons of local inhibitory interneurons as well. Parvalbumin positive basket cells (PV+ BCs) are fast spiking interneurons which are prominent in the hippocampus where they contribute to the synchrony of action potentials of large populations of neurons. They function as clockworks that drive network oscillations such as sharp wave ripples, are critical for memory consolidation, and are highly abundant in hippocampal area CA2. Whether myelination of the CA2 PV+ BC axon plays a role in their temporally precise inhibitory function, and whether this supports temporally precise neuronal encoding and cognitive performance remains obscure. In this Marie Skłodowska-Curie fellowship, I will address this question by combining my expertise in subcellular patch-clamp methods with the expertise of the host on Ca2+ imaging, myelin physiology, and in vivo electrophysiology. The proposed multimethod and multidisciplinary study will be unique in showing how biophysical changes in small neuronal compartments will lead to alterations of neuronal networks and ultimately to behavioral alterations of the organism. The fellowship is expected to provide me with transferable skills and high throughput techniques that will greatly improve my chances to become an influential leader in the field of neuroscience.