Exploring the role of de novo myelination in engram formation

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Learning and memory formation are crucial functions to adapt to outside experience. At the circuit level, memories are stored in neuronal ensembles that correspond to an engram (or memory trace). Recently glial cells have been shown to modulate memory function. Oligodendrocytes, in particular, have become a focus of research as recent studies have shown that enhancing or inhibiting oligodendrocyte precursors (OPCs) proliferation and differentiation (adult oligodendrogenesis) impacts memory formation and consolidation. In this project, I first want to elucidate the effect of adult oligodendrogenesis on engram formation by investigating how disrupting oligodendrogenesis alters the engram formed by contextual fear conditioning. Using engram tagging and optogenetic manipulation of neuronal activity I will answer the question whether adaptive myelination leads to a stronger allocation of neurons to the network or whether reactivation of the engram is promoted.My second aim is to shed light on how neuronal activity induces OPCs to start differentiating and myelinating. Which signalling pathways are the downstream effectors of neuronal activity in OPCs? Neurotransmitter receptors expressed by OPCs may transduce the signal given by neuronal activity and a possible downstream effector may be Ca2+-signalling. I will examine OPC Ca2+-dynamics induced by artificial stimulation of a specific long-range projection and during actual memory formation using two-photon and one-photon in vivo Ca2+-imaging, respectively. Furthermore, I will impair the Ca2+-dynamics in OPCs to determine whether Ca2+-signalling is the driving force behind OPC response to neuronal activity. In summary, I will shed a light on the influence of adaptive myelination on engram formation and determine whether Ca2+-signalling is a crucial factor in adult oligodendrogenesis. Elucidating the contribution of OPCs to engram formation will enhance our understanding of how learning and memory formation is facilitated at cellular and circuit level.