Fragile X Mental Retardation Protein Regulates Olfactory Sensitivity But Not Odorant Discrimination

Abstract

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is characterized by cognitive impairments and altered sensory function. It is caused by absence of fragile X mental retardation protein (FMRP), an RNA-binding protein essential for normal synaptic plasticity and function. Animal models have provided important insights into mechanisms through which loss of FMRP impacts cognitive and sensory development and function. While FMRP is highly enriched in the developing and adult olfactory bulb (OB), its role in olfactory sensory function remains poorly understood. Here, we used a mouse model of FXS, the fmr1 (-/y) mouse, to test whether loss of FMRP impacts olfactory discrimination, habituation, or sensitivity using a spontaneous olfactory cross-habituation task at a range of odorant concentrations. We demonstrated that fmr1 (-/y) mice have a significant decrease in olfactory sensitivity compared with wild type controls. When we controlled for differences in sensitivity, we found no effect of loss of FMRP on the ability to habituate to or spontaneously discriminate between odorants. These data indicate that loss of FMRP significantly alters olfactory sensitivity, but not other facets of basal olfactory function. These findings have important implications for future studies aimed at understanding the role of FMRP on sensory functioning.

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

“…In contrast, Fmr1 -/y mice (20) did not learn to discriminate the two odorants after a 10day enrichment period ( Fig.1D and supplementary Fig.S1C). This was not due to a general olfactory discrimination defect of the knocked-out (KO) mice since they spontaneously discriminated two perceptually distinct odorants (Octanal/Carvone, supplementary Fig.S1D) and as previously described (21). This suggests that FMRP is necessary for the perceptual learning underlying discrimination of similar odorants.…”

Visual Behavior Impairments as an Aberrant Sensory Processing in the Mouse Model of Fragile X Syndrome

“…Neurosensorial abnormalities are a strong phenotype of the FXS conditions. Indeed, odorant sensitivity (Schilit Nitenson et al, 2015) and nociceptive responses after a local acute inflammation (Price et al, 2007; Busquets-Garcia et al, 2013) are significantly lower in the FXS model whereas an excessive excitability of auditory processing (Garcia-Pino et al, 2017) and an exaggerated response to whisker stimulation (He et al, 2017) were observed. Regarding vision, few data were reported and they were associated to cognitive mechanism such as the Fmr1 −/y delayed learning on visual discrimination tasks (Goel et al, 2018).…”

Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

“…Indeed, hypersensitivity phenotypes have been demonstrated for audition aspects as well as for visual responses since Fmr1 −/y mice present hyper arousal excitability for auditory processing and exacerbated transmission between photoreceptors and the inner retina (as observed in our experiment), respectively. But tactile nociception after local acute inflammation is lowered (Price et al, 2007 ; Busquets-Garcia et al, 2013 ), and Fmr1 −/y mice present a significant decrease in odorant sensitivity (Schilit Nitenson et al, 2015 ). Consequently, we propose that the most relevant terminology to characterize this complex sensorial spectrum is “dys-sensitivity phenotype” instead of “hyper-sensitivity phenotype”.…”