| First Author | Daroles L | Year | 2016 |
| Journal | Biol Psychiatry | Volume | 80 |
| Issue | 2 | Pages | 149-159 |
| PubMed ID | 26372002 | Mgi Jnum | J:283961 |
| Mgi Id | MGI:6378712 | Doi | 10.1016/j.biopsych.2015.07.023 |
| Citation | Daroles L, et al. (2016) 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. Biol Psychiatry 80(2):149-159 |
| abstractText | 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 (alphaCaMKII) mutant mice with altered dendritic localization of alphaCaMKII messenger RNA, as well as a reporter of alphaCaMKII 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 alphaCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of alphaCaMKII 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 alphaCaMKII 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. |
