CART pilot grant recipient to study sensory over-reactivity in Fragile X Syndrome

Dr. Carlos Portera-Cailliau

Individuals with autism spectrum disorders (ASD) process sensory stimuli differently than their neurotypical counterparts. For example, they may feel overwhelmed by certain smells, touches or sights that would seem innocuous to others. This sensory over-reactivity can lead to feelings of anxiety that negatively impact activities of daily living and contributes to distraction, attention deficit and impaired learning. Sensory symptoms in ASD are also predictive of the subsequent appearance of impaired social behavior and other autistic traits. We have focused our studies on Fragile X syndrome (FXS), which is the most common inherited form of autism and intellectual disability because the vast majority of individuals with FXS suffer from impaired sensory processing and exhibit avoidance behaviors to what they perceive as aversive stimuli. We have sought to uncover alterations in brain circuits that lead to atypical sensory processing in FXS. Recently, we and others demonstrated that the activity of parvalbumin (PV) inhibitory neurons (which normally dampen and modulate overall brain activity) is diminished in an experimental model (Fmr1-/-) of FXS. Furthermore, we discovered that we could reverse certain symptoms of FXS in this model by restoring the activity of PV neurons to normal levels. This suggests that understanding the causes of PV neuron dysfunction could help identify novel treatments for FXS and other ASDs. Here, we propose to investigate whether the genes expressed by PV neurons are perturbed in FXS. This will be done using the latest approaches (Ribo-TAG and high-throughput RNA sequencing). This pilot grant will serve as a basis for future larger-scale studies to understand changes in gene expression in FXS and other ASDs after learning.

Dr. Carlos Portera-Cailliau is a recipient of the 2019-2020 CART Pilot Grant. He is a professor in Neurology and Neurobiology at UCLA.

The UCLA CART Pilot Grant funds one-year pilot and/or feasibility studies for biomedical, epidemiological, or behavioral research. The purpose of these awards is to foster interactions and interdisciplinary research projects in the basic and clinical areas of autism. This funding has been made available through support by the UCLA Department of Psychiatry and Biobehavioral Sciences, the UCLA Clinical and Translational Science Institute (CTSI), and UCLA Intellectual and Developmental Disabilities Research Center.