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Michel, F.

Publications and source records attributed to Michel, F..

2 recordsLinked to original sources

Mature dentate granule cells show different intrinsic properties depending on the behavioural context of their activation

The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the large majority remains silent. To date, the properties of this active subset of neurons remain poorly investigated. Using fosGFP transgenic mice, we show ex vivo that activated mDGCs, from mice maintained in their home cage, exhibit a marked lower intrinsic excitability compared to the non-activated cells. Remarkably, activated mDGCs, from mice trained in a virtual environment, are more excitable than those from mice maintained in their home cage. Therefore, we show that activated mDGCs display different intrinsic properties and excitable states depending on the context of their activation. We propose that these properties could constitute a neural signature of cell assemblies recruited in different behavioral contexts.

neuroscience

Compound signaling activates endogenous retroviruses by inducing enhancer and gene-neighborhood transcription

SummaryMultiple sclerosis (MS) is a neuroinflammatory and autoimmune disease, in which various immune cell types and autoreactive T cells exert a pathogenic activity. This disease is also associated with increased transcription of several endogenous retroviruses (HERVs) normally kept in check by heterochromatin. Here, we have uncovered an organic pollutant dieldrin that activates several HERVs associated with MS and allowing us to examine the mechanism of their activation. Dieldrin singles out by its ability to simultaneously activate the MAP kinase and the PI3K pathways, while also triggering calcium dependent peptidylarginine deiminase activity. It was this association of pathways that caused HERV activation, a phenomenon that was only part of more generally increased transcription of heterochromatic regions. The HERV transcripts were generally not polyadenylated. Some arose as a consequence of activation of HERV-based enhancers, while others were the result of unusually strong activation at some mostly transcription factor genes causing transcription to leak out of the HERV-free region that surrounds them. Altogether, our data emphasized the hazard associated with simultaneous activation of multiples signaling pathways by xenobiotics, while also providing a very general toolbox for the interpretation of HERV transcription.

molecular biology