ArticleCurrent biology : CB2017
Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome.
Article in Current biology : CB, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 52 citations in OpenAlex.
- Dynamics of two distinct memory interactions during water seeking inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nonlinear high-activity neuronal excitation enhances odor discrimination.Current biology : CB · 2025Article
- Altered olfactory responses in Fmr1 KO mice.Scientific reports · 2025Article
- Serotonin acts through multiple cellular targets during an olfactory critical period.iScience · 2024Article
- Deficits in olfactory system neurogenesis in neurodevelopmental disorders.Genesis (New York, N.Y. : 2000) · 2024Review
- Hyperexcitability in the Olfactory Bulb and Impaired Fine Odor Discrimination in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Review
- A simple high-throughput method for automated detection of Drosophila melanogaster light-dependent behaviours.BMC biology · 2022Article
- Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome.Communications biology · 2022Article
- Exposure to GABAFrontiers in psychiatry · 2022Article
- Experience-dependent plasticity modulates ongoing activity in the antennal lobe and enhances odor representations.Cell reports · 2021Article
- Review
- Neuron-Specific FMRP Roles in Experience-Dependent Remodeling of Olfactory Brain Innervation during an Early-Life Critical Period.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Hyperexcitability and Homeostasis in Fragile X Syndrome.Frontiers in molecular neuroscience · 2021Article
- Genetic background mutations drive neural circuit hyperconnectivity in a fragile X syndrome model.BMC biology · 2020Article
- Interhemispheric connections between olfactory bulbs improve odor detection.PLoS biology · 2020Article
- Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome.Translational psychiatry · 2019Article
- Activity-Dependent Remodeling ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Haploinsufficiency of autism causative geneMolecular autism · 2019Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Fragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS flies exhibit strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor specific due to broader response tuning of excitatory projection neurons. We find that impaired inhibitory interactions underlie reduced specificity in olfactory computations. Finally, we show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. We provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of FXS. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability.
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