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Gene expression mechanisms involved in brain plasticity

Our research focuses on the exploration of novel pathways for rapid gene regulation, which are important for neuronal plasticity.

We have an amazing ability to learn and adapt to our environment throughout life. This capability is supported by the exceptional plasticity of the brain. During learning and with experiences, neuronal networks are modified to support the acquisition of new skills. Our goal is to obtain a molecular understanding of how neuronal activity and modifications can trigger rapid functional changes of neuronal networks.

Storage and release of DNA copies
We know that visual stimuli can induce the expression of particular genes thereby allowing a modification of neuronal networks. But conventional gene expression pathways require hours, and many neuronal plasticity events occur on a much faster timescale.

We recently discovered a novel mechanism for the rapid regulation of gene expression in neuronal cells. It relies on the temporal storage of highly stable and almost mature RNAs in the cell nucleus and their stimulus-dependent release within few minutes. This controlled release of transcripts is enabled by a specific form of RNA processing. More precisely, the RNA storage-release is gated by the retention-excision of RNA elements called introns that have to be removed to generate a mature RNAs. We are now applying a combination of transcriptome-wide analysis, and high-resolution imaging in the mouse brain to investigate this novel mechanism.

New insights for pathological states
Our research highlighted an unexpected role for alternative RNA processing in neuronal gene regulation, in particular in activated neurons. Alterations in the ability of neurons to undergo plasticity and to modify their function during learning processes is one of the key features underlying neurological disorders. Thus, in the long term, we hope to apply our insights into this novel mechanism to the exploration of pathological states as well as the development of therapeutic interventions.

Team

PhD Students

Publications

2017

Mauger, Oriane; Scheiffele, Peter (2017). Beyond proteome diversity: alternative splicing as a regulator of neuronal transcript dynamics. Current Opinion in Neurobiology, 45, 162-168.

2016

Mauger, Oriane; Lemoine, Frédéric; Scheiffele, Peter (2016). Targeted Intron Retention and Excision for Rapid Gene Regulation in Response to Neuronal Activity. Neuron, 92 (6), 1266-1278.


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