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.

Keywords: FMRP; behavior; discrimination; mouse; olfaction; sensitivity.

Figure 1.

Loss of fmr1 does not impact olfactory habituation. Five odorants were averaged to create the investigation time presented. Investigation time (±SEM) is plotted across the 4 habituation trials (Hab1-4) for (a) the lowest detected concentration and (b) highest discriminated concentration of odorants tested for WT and fmr1 ^−/y mice. Statistical comparison were carried out using a 1-way ANOVA, main effect of trial, ***P ≤ 0.001.

Figure 2.

Olfactory discrimination ability is concentration- and genotype-dependent. Bar graphs plotting the average investigation time (±SEM) for the Hab4 = final habituation, S1 = strongly similar, S2 = moderately similar, D = dissimilar odorant trials. Data is presented for (a) WT and (b) fmr1^−/y mice. Five unique odorants were used for each novel trial. Statistical comparisons were carried out with GLM repeated measures ANOVA, with post hoc comparisons and Bonferoni corrections for multiple tests, **P < 0.01, ***P ≤ 0.001.