FMRP and dendritic local translation of αCaMKII mRNA are required for the structural plasticity underlying olfactory learning

Laura Daroles (1) , Simona Gribaudo (1) , Mohamed Doulazmi (1) , Sophie Scotto-Lomassese (1) , Caroline Dubacq (1) , Nathalie Mandairon (2) , Charles August Greer (3) , Anne Didier (2) , Alain Trembleau (1) , Isabelle Caillé (4, 1)

1 NPS - Neuroscience Paris Seine
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 Department of neurosurgery
4 UPD7 - Université Paris Diderot - Paris 7

Background In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In Fragile X Syndrome (FXS), the absence of Fragile X Mental Retardation Protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. Methods Using an olfactory learning task requiring adult-born olfactory bulb (OB) neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used αCaMKII mutant mice with altered dendritic localization of αCaMKII mRNA as well as a reporter of αCaMKII local translation to investigate the role of this FMRP mRNA target in learning-dependent structural plasticity. Results Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an mGLUR5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. Conclusion Our results strongly suggest that FMRP mediates structural plasticity of OB adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which FXS is the primary monogenic cause.

Mots clés: Fragile X Mental Retardation Protein; local translation; adult neurogenesis; olfactory bulb; structural plasticity; learning

Domaines: Neurosciences [q-bio.NC]

Laura Daroles, Simona Gribaudo, Mohamed Doulazmi, Sophie Scotto-Lomassese, Caroline Dubacq, et al.. FMRP and dendritic local translation of αCaMKII mRNA are required for the structural plasticity underlying olfactory learning. Biological Psychiatry, 2015, 80 (2), pp.149-159. ⟨10.1016/j.biopsych.2015.07.023⟩. ⟨hal-01188827⟩