Role of FMRP in the differentiation and integration of adult-born neurons in the mouse olfactory bulb
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1
UPMC, Universite Paris 7, UMR 7102, Equipe Developpement et Plasticite des Reseaux Neuronaux, France
FMRP (Fragile X Mental Retardation Protein) is a key regulator of dendritic local translation in response to activity. Its absence, due to the silencing of its gene Fmr1, leads to the most common inherited form of mental retardation, Fragile X Syndrome (FXS). FXS patients and Fmr1-/- mice both display defects in structural and functional plasticity, such as an increased density of immature spines and impairment in LTD and LTP. The current study addresses the role of FMRP in the processes of dendritic growth, spine formation and synaptogenesis of the well-characterized newly generated granule cells (GC) of the adult olfactory bulb (OB). Newborn GCs are produced in the subventricular zone of the lateral ventricle (SVZ), and migrate through the rostral migratory stream to integrate the OB. The distance between site of production and differentiation provides the possibility to genetically manipulate the progenitors of newly formed neurons and investigate the effects of the introduced mutation on their differentiation. To knockdown Fmr1, we thus designed and produced lentiviruses coexpressing GFP and a shRNA against Fmr1. In vitro, infection of N2A cells with this lentivirus leads to a 92.3% reduction of Fmr1 mRNA, as compared to a control lentivirus. In vivo, 15 days after SVZ infection, the percentage of GFP+ newborn GCs, which are FMRP immunoreactive, is divided by 3.2 in the shFMR1 infected animals as compared to the control. We will analyse the consequences of such Fmr1 invalidation on the morphological and electrophysiological characteristics of newborn GCs, at different times after their birth in the SVZ. Preliminary results show that 21 days after their birth, the invalidated GCs display more numerous and immature looking spines, which is very reminiscent of the defects observed in the brain of FXS patients. Detailed analysis will give us the unique opportunity to monitor FMRP function in the process of differentiation, integration and plasticity in a subset of neurons inside a mature wild-type network. This will also allow us to evaluate a potential role of local translation in the regulation of adult neurogenesis.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Oral Presentation
Topic:
Symposium 03 – Cellular regulation of adult-born neurons and their stem cells
Citation:
Scotto-Lomassese
S,
Trembleau
A and
Caille
I
(2009). Role of FMRP in the differentiation and integration of adult-born neurons in the mouse olfactory bulb.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.021
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Received:
19 Nov 2009;
Published Online:
19 Nov 2009.
*
Correspondence:
Sophie Scotto-Lomassese, UPMC, Universite Paris 7, UMR 7102, Equipe Developpement et Plasticite des Reseaux Neuronaux, Paris, France, sophie.scotto@snv.jussieu.fr