Analysis of changes in protein expression in inferior colliculus

One of the most robust behavioural phenotypes in the Fmr1-/ymouse is an increased susceptibility to AGS, which models the sensory hypersensitivity and epileptiform activity seen in FX patients (Berry-Kravis, 2002; Musumeci et al., 1991; Yan et al., 2004; Yan et al., 2005). Multiple therapeutic strategies that alleviate AGS have gone on to be tested in clinical studies, suggesting this assay has predictive value (Liu and Smith, 2014; Michalon et al., 2012; Osterweil et al., 2013; Pacey et al., 2009). Recent studies implicate the inferior colliculus (IC) as a central mediator of the AGS phenotype. The IC is a central hub for auditory processing, relaying information from brainstem nuclei to the auditory cortex and other brain regions (Ayala et al., 2016). In the Fmr1-/ymouse, auditory stimulation causes an enhanced activation of IC neurons as assessed by cFos+ staining and in vivosingle-unit recordings (Nguyen et al., 2020). Moreover, studies using conditional expression of Fmr1in specific neuronal populations show that loss of FMRP in glutamatergic VGlut2+ neurons in the IC is both necessary and sufficient for AGS induction (Gonzalez et al., 2019). We aim to test whether changes in proteasome activity is seen in the Fmr1-/y IC, and if so whether modulating UPS activity could resolve pathological changes.