Hyperexcitability in the Olfactory Bulb and Impaired Fine Odor Discrimination in the KO Mouse Model of Fragile X Syndrome

Significance Statement: Fragile X syndrome (FXS) in humans is associated with a range of debilitating deficits including aberrant sensory processing. One sensory system that has received comparatively little attention in studies in animal models of FXS is olfaction. Here, we report the first comprehensive physiological analysis of circuit defects in the olfactory bulb in the commonly-used knockout (KO) mouse model of FXS. Our studies indicate that KO alters the local excitation/inhibition balance in the bulb - similar to what KO does in other brain circuits - but through a novel mechanism that involves enhanced feedforward excitatory drive. Furthermore, KO mice display behavioral impairments in fine odor discrimination, an effect that may be explained by enhanced neural excitability.