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The Summer Student Fellowship was established to encourage a new generation of Fragile X researchers. By funding young scientists’ research pursuits, we believe that it will continue to push Fragile X into exciting new territory and inspire them to continue important work in this field.

These are the results of this year’s research projects:

Testing MicroRNA-Mediated Silencing of Kv4.2 as Therapeutic Target in an Fragile X Syndrome Mouse Model

Joseph Krzeski
Supervisor: Christina Gross, PhD

Fragile X syndrome (FXS) is characterized by the dysregulation of proteins possibly due to the loss of Fragile X Mental Retardation Protein. This causes some patients with FXS to exhibit neuronal hyperexcitability and epilepsy. Working with Dr. Christina Gross, Joseph observed the levels of Kv4.2, a membrane channel in neurons, in FXS mice when a certain cellular regulator was blocked and the effects this had on FXS mouse behavior. Initial experiments suggest that blocking the treatment had no effect on Kv4.2 levels and did not reverse aberrant mouse behavior. In the future, Joseph will explore the inhibition of this regulator on other proteins related to FXS, as well as on the increased susceptibility to audiogenic seizures.

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Evaluation of a Direct Outcome Measure of Social Interaction in Children and Adults with Fragile X Syndrome

Mika and Jenna Nagamoto
Supervisor: Nicole Tartaglia, MD

The goal of this study was to evaluate a new outcome measure of social interaction called the ASIEP (Autism Screening Instrument for Educational Purposes). During ASIEP sessions, patients with FX were videotaped while they played with the examiner. The videos were then scored for different social interactions. ASIEP scores were compared to results of other measures of social functioning. Preliminary results show that all participants enjoyed the play interaction and were able to complete the session with valid scores, supporting that the ASIEP is promising as an efficient measure of social skills for FX clinical trials. Mika and Jenna were inspired by FX families and are now dedicated to the promotion of FX awareness as they pursue their professional careers.

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Activity-dependent Dysfunction of Microglia in Fragile X Syndrome

Chandler Robinson
Supervisor: Craig A. Erickson, MD

This project investigated the functional ability of microglia to remodel synaptic connections in an activity dependent manner, utilizing the developing retinogenticulate system in Fmr1 KO mice, as well as characterizing alterations in microglia density and morphology in brain regions undergoing high levels of synaptic pruning in Fmr1 KO mice compared to adults. Through this daunting project, Chandler developed new skills and continues to push this project forward and is excited to see the results in the months to come.

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Understanding the Role of Agranular Insular Cortex Projections to the Nucleus Accumbens in the Pathogenesis of Blunted Social Affect in Fragile X

Seokyu (Philip) Shin
Supervisor: Gül Dölen, MD, PhD

Autism spectrum disorder (ASD) afflicts 1 in 68 children in the United States, and yet its pathogenesis is still unclear, and there is no known cure. ASD is characterized by core deficits in social function, including disrupted social cognition and blunted social affect. Therefore, the first step in understanding disease pathogenesis is studying the neural circuitry behind these social functions. In order to understand how disrupted social aversion circuits lead to blunted social effect, the Dölen lab has developed a novel behavioral assay: inequity-induced group segmentation (iGS). Here, triads of mice that have been socially housed since weaning, are water restricted one week after weaning. Water is given to them for ten minutes per day in a 3-way, transparently divided, inequity conditioning chamber. Two mice, in the “in-group”, are allotted only 1mL of water per day, while one mouse, the out-group, is allotted as much water as it wants during the 10-minute period. After two weeks of such inequity conditioning, social motivation is studied using place conditioning. Preliminary data suggest that in wild-type mice, in-group mice show robust social place preference, while out-group mice display social conditioned place aversion. These results suggest that iGS may be a useful behavioral assay for studying blunted social effect in Fmr1 KO mouse model of Fragile X and autism.

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