Establishment, maintenance and plasticity of synapses rely on the dynamic regulation cell adhesion molecules. Here, we will decipher the molecular mechanisms involved in the control of synaptic adhesion molecules investigating three levels of regulation : (i) DNA methylation, (ii) transcriptomic activity and (iii) miRNA translational inhibition. In addition, we will take advantage of recent technological developments to investigate these mechanisms at the single-cell level using the Patch-Seq approach.

 

This project is based on our expertise in the epigenetic/transcriptomic regulation of the neuronal function. Indeed, we previously demonstrated the key role of miRNAs in the regulation of neuronal activity in animal models of chronic pain (Favereaux et al. 2011) and cancer pain (Elramah et al. 2017, Lopez-Gonzalez et al. ). In addition, we showed that miRNAs can regulate the translation of AMPA receptors locally in the dendrites in response to activity changes (Letellier et al. 2014). Recently, we demonstrated the interplay between miRNAs and target mRNAs for the specification of brain areas (Soula et al. 2018).

 

We will use two models:

(i) the developing cerebellum which undergoes an intense synapse selection during the first post-natal days.

(ii) the homeostatic plasticity paradigm in the hippocampus which demonstrates dynamic and subtle adaptation of the synaptic force in response to activity modulations.

Correlating morphology, electrophysiology and transcriptomic state at the single neuron level using the Patch-Seq technique should highlight the key regulations of adhesion molecules sustaining synaptic plasticity.

 

References:

- Small RNA-Seq reveals novel miRNAs shaping the transcriptomic identity of rat brain structures. Soula A, Valere M, Lopez-Gonzalez MJ, Ury-Thiery V, Groppi A, Landry M, Nikolski M, Favereaux A. Life Sci Alliance. 2018 Sep 30;1(5):e201800018. Doi: 10.26508.

- Oxaliplatin treatment impairs extension of sensory neuron neurites in vitro through miR-204 overexpression. López-González MJ, Soula A, Landry M, Favereaux A. Neurotoxicology. 2018 Sep;68:91-100.

- Spinal miRNA-124 regulates synaptopodin and nociception in an animal model of bone cancer pain. Elramah S, López-González MJ, Bastide M, Dixmérias F, Roca-Lapirot O, Wielanek-Bachelet AC, Vital A, Leste-Lasserre T, Brochard A, Landry M, Favereaux A. Sci Rep. 2017 ;7(1):10949.

- miR-92a regulates expression of synaptic GluA1-containing AMPA receptors during homeostatic scaling. Letellier M*, Elramah S*, Mondin M, Soula A, Penn A, Choquet D, Landry M, Thoumine O*, Favereaux A*. Nat Neurosci. 2014; 17(8):1040-2.

- Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. Favereaux A, Thoumine O, Bouali-Benazzouz R, Roques V, Papon A, Abdel Salam S, Drutel G, Léger C, Calas A, Nagy F, Landry M. EMBO J. 2011; 30(18):3830-41.