Stress Odorant Sensory Response Dysfunction in Drosophila Fragile X Syndrome Mutants

• Published in: Frontiers in molecular neuroscience Vol. 11; p. 242
• Main Authors: Androschuk, Alaura, He, Richard X, Weber, Savannah, Rosenfelt, Cory, Bolduc, Francois V
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 08.08.2018; Frontiers Media S.A
• Subjects: Autism; avoidance response; Behavior; cAMP; cGMP; Cognitive ability; Cyclic AMP; Cyclic GMP; Drosophila; FMR1 protein; Fragile X syndrome; Guanosine; Information processing; Insects; Intellectual disabilities; Kinases; Laboratories; Memory; Mushroom bodies; Neuroscience; NMR; Nuclear magnetic resonance; Protein kinase A; Proteins; Sensory integration; Sensory perception; sensory response dysfunction; Stress; Canada; avoidance response; sensory response dysfunction; Drosophila; IBMX; cGMP; Fragile X syndrome; cAMP
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2018.00242

Sensory processing dysfunction (SPD) is present in most patients with intellectual disability (ID) and autism spectrum disorder (ASD). Silencing expression of the Fragile X mental retardation 1 ( ) gene leads to Fragile X syndrome (FXS), the most common single gene cause of ID and ASD. have a highly conserved FMR1 ortholog, . mutants display cognitive and social defects reminiscent of symptoms seen in individuals with FXS. We utilized a robust behavioral assay for sensory processing of the stress odorant (dSO) to gain a better understanding of the molecular basis of SPD in FXS. Here, we show that mutant flies present significant defects in dSO response. We found that expression in mushroom bodies is required for dSO processing. We also show that cyclic adenosine monophosphate (cAMP) signaling via PKA is activated after exposure to dSO and that several drugs regulating both cAMP and cyclic guanosine monophosphate (cGMP) levels significantly improved defects in dSO processing in mutant flies.