ArticleNeurobiology of disease2014
GABAergic circuit dysfunction in the Drosophila Fragile X syndrome model.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Hippocampal Astrocytes Impact Postnatal Development of Inhibitory Connections, Parvalbumin Levels, Social, and Spatial Navigation Behaviors in a Mouse Model of Fragile X Syndrome.Journal of neurochemistry · 2026Article
- Astrocytic GABA controls fidelity of temporal cortical processing in Fragile X Syndrome.Neurobiology of disease · 2026Article
- Skewing information flow through pre- and postsynaptic plasticity in the mushroom bodies ofLearning & memory (Cold Spring Harbor, N.Y.) · 2024Review
- Drosophila expressing mutant human KCNT1 transgenes make an effective tool for targeted drug screening in a whole animal model of KCNT1-epilepsy.Scientific reports · 2024Article
- Hyperexcitability in the Olfactory Bulb and Impaired Fine Odor Discrimination in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Asynchronous transcription and translation of neurotransmitter-related genes characterize the initial stages of neuronal maturation in Drosophila.PLoS biology · 2023Article
- A perspective on molecular signalling dysfunction, its clinical relevance and therapeutics in autism spectrum disorder.Experimental brain research · 2022Review
- Functional assessment of the "two-hit" model for neurodevelopmental defects in Drosophila and X. laevis.PLoS genetics · 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
- Fragile X syndrome and associated disorders: Clinical aspects and pathology.Neurobiology of disease · 2020Review
- Intellectual disability and autism spectrum disorders 'on the fly': insights fromDisease models & mechanisms · 2019Review
- Dissecting the Genetics of Autism Spectrum Disorders: AFrontiers in physiology · 2019Review
- Structural and Functional Abnormalities in the Olfactory System of Fragile X Syndrome Models.Frontiers in molecular neuroscience · 2019Review
- Synaptopathology Involved in Autism Spectrum Disorder.Frontiers in cellular neuroscience · 2018Review
- Impaired GABA Neural Circuits Are Critical for Fragile X Syndrome.Neural plasticity · 2018Review
- Modeling Fragile X Syndrome inFrontiers in molecular neuroscience · 2018Review
- Drosophila Studies on Autism Spectrum Disorders.Neuroscience bulletin · 2017Review
- Multifarious Functions of the Fragile X Mental Retardation Protein.Trends in genetics : TIG · 2017Review
- ESCRT-III Membrane Trafficking Misregulation Contributes To Fragile X Syndrome Synaptic Defects.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fragile X syndrome (FXS), caused by loss of FMR1 gene function, is the most common heritable cause of intellectual disability and autism spectrum disorders. The FMR1 protein (FMRP) translational regulator mediates activity-dependent control of synapses. In addition to the metabotropic glutamate receptor (mGluR) hyperexcitation FXS theory, the GABA theory postulates that hypoinhibition is causative for disease state symptoms. Here, we use the Drosophila FXS model to assay central brain GABAergic circuitry, especially within the Mushroom Body (MB) learning center. All 3 GABAA receptor (GABAAR) subunits are reportedly downregulated in dfmr1 null brains. We demonstrate parallel downregulation of glutamic acid decarboxylase (GAD), the rate-limiting GABA synthesis enzyme, although GABAergic cell numbers appear unaffected. Mosaic analysis with a repressible cell marker (MARCM) single-cell clonal studies show that dfmr1 null GABAergic neurons innervating the MB calyx display altered architectural development, with early underdevelopment followed by later overelaboration. In addition, a new class of extra-calyx terminating GABAergic neurons is shown to include MB intrinsic α/β Kenyon Cells (KCs), revealing a novel level of MB inhibitory regulation. Functionally, dfmr1 null GABAergic neurons exhibit elevated calcium signaling and altered kinetics in response to acute depolarization. To test the role of these GABAergic changes, we attempted to pharmacologically restore GABAergic signaling and assay effects on the compromised MB-dependent olfactory learning in dfmr1 mutants, but found no improvement. Our results show that GABAergic circuit structure and function are impaired in the FXS disease state, but that correction of hypoinhibition alone is not sufficient to rescue a behavioral learning impairment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.