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Biol Psychiatry. 2016 Jul 15;80(2):149-159. doi: 10.1016/j.biopsych.2015.07.023. Epub 2015 Aug 7.

Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning.

Author information

1
Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 06, Centre National de la Recherche Scientifique UMR8246, INSERM U1130, IBPS, Neuroscience Paris Seine, France.
2
Université Lyon1, CNRS UMR 5292, INSERM U1028, Centre de Recherche en Neurosciences de Lyon.
3
Yale University School of Medicine, Department of Neurosurgery, New Haven, Connecticut.
4
Sorbonne Universités, Université Pierre et Marie Curie Univ Paris 06, Centre National de la Recherche Scientifique UMR8246, INSERM U1130, IBPS, Neuroscience Paris Seine, France; Sorbonne Paris Cité, Université Paris Diderot-Paris 7. Electronic address: isabelle.caille@snv.jussieu.fr.

Abstract

BACKGROUND:

In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, 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 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 alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA 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 metabotropic glutamate receptor 5 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.

CONCLUSIONS:

Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb 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 fragile X syndrome is the primary monogenic cause.

KEYWORDS:

Adult neurogenesis; Fragile X mental retardation protein; Learning; Local translation; Olfactory bulb; Structural plasticity

PMID:
26372002
DOI:
10.1016/j.biopsych.2015.07.023
[Indexed for MEDLINE]

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