University Honors

Fragile X Syndrome (FXS), a genetic mutation, is a leading cause of attention andlearning related disorders such as Autism Spectrum Disorder (ASD). However, the question ofhow dysfunctional mechanisms contribute to symptoms related to FXS remains unclear. Priorstudies have shown that mice with FXS have an increase in cholinergic signaling. Cholinergicinput allows sensory responses to occur in a more reliable way, and therefore when elevatedatypically can lead to hyperarousal and deficits in learning. Our research goal is to examine thecircuit defects that cause an increase in cholinergic input and determine if a reduction incholinergic signaling to the primary visual cortex (V1) will rescue visual perceptual learning. Wewill use Fmr1–/– knockout (KO) mice, which is an established mouse model of FXS and sharessimilarities in sensory and learning issues observed in humans with FXS. Wild type (WT) mice,with neurotypical brain circuits will be used as controls. We will use a genetically encodedcalcium indicator in combination with two photon microscopy to examine changes in cholinergicfunction. We will also observe locomotion and pupil dilation of the mouse during stimuluspresentation to determine arousal and engagement. Our hypothesis is that an elevation in basallevels of cholinergic input from subcortical areas to V1 in Fmr1–/– mice will prevent V1 neuronsfrom responding selectively to visual stimuli, thus contributing to impaired learning. We alsoexpect to see an increase in engagement and arousal as measured by locomotion and pupildiameter in Fmr1–/– mice. The results from this study will inform therapies that can be targeted tospecific circuits in ASD and FXS symptoms.