Title: Studying neuronal circuit mechanisms underlying fragile X syndrome in Drosophila melanogaster
Other Titles: Studie van de onderliggende neuronaal circuit mechanismen bij het fragiele-X-syndroom in Drosophila Melanogaster
Authors: Franco Méndez, Luis Manuel
Issue Date: 14-Oct-2016
Abstract: Summary
Fragile X syndrome patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An exciting hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of fragile X syndrome. Here, I directly test this idea. First, I show that a Drosophila melanogaster model of fragile X syndrome exhibits strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor-specific due to broader response tuning of excitatory projection neurons. I find that impaired inhibitory interactions underlie reduced specificity in olfactory representations. Finally, I show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. I provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of fragile X syndrome. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability.
Publication status: accepted
KU Leuven publication type: TH
Appears in Collections:Laboratory of Neurogenetics
Research Group Neurophysiology
Department of Human Genetics - miscellaneous
Epidemiology Research Group (+)

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