Exploring the role of de novo myelination in engram formation
Experimental and Theoretical Network Neuroscience
Final Report Abstract
In this study, we investigated the role of OPCs and adaptive myelination on memory formation at the engram level. We inhibited adaptive myelination by knocking out the transcription factor Myrf. The attempt to label the fear conditioning-formed engram using the RAM tagging system in conjunction with a Flp-ase yielded indiscriminate tagging across all transduced neurons, allowing no conclusion on the impact of how loss of adaptive myelination affects the engram. Furthermore, we theorised that Ca2+ may serve as a downstream mediator of neuronal activity in OPCs, potentially driving adaptive myelination. Leveraging the DREADD receptor HM4di known for inhibiting Ca2+ activity, we used a mouse line in which Hm4Di expression is confined to OPCs. After administering C21 or only water for four weeks, we assessed whether the rate of adaptive myelination differed in Hm4Di-expressing mice compared to control mice. Surprisingly, we did not observe any change in the rate of adaptive myelination, suggesting that Ca2+ may not play a role in this process in OPCs. There is, however, the possibility of Hm4di acting differently in OPCs compared to in neurons, potentially failing to inhibit Ca2+ signalling in OPCs. This analysis revealed a significant higher OPC density within two specific hippocampal regions, notably in the hilus of the dentate gyrus (DG) and the stratum lucidum of CA3. We postulated that OPCs in the DG and the stratum lucidum of CA3 may play a role in axon guidance and circuit integration of adult-born neurons. Indeed, we observed a tight association between OPCs and newborn neurons including synapses formed by newborn neurons onto OPCs. Presently, our ongoing efforts aim to quantify these synapses and discern potential differences in their numbers between embryonically born neurons and newborn neurons. In summary, these findings offer valuable insights into the intricate dynamics between oligodendroglial lineage, neuronal activity, and the processes underlying memory formation.
Publications
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3rd Neurogenesis Conference, Implications for Lifelong Development and Disease
Marie-Theres Wittmann
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Tagging and Manipulation of Fear Engrams. Neuromethods, 235-246. Springer US.
Wittmann, Marie-Theres; Rashid, Asim J.; Josselyn, Sheena A. & Frankland, Paul W.
