Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of Fragile X syndrome

Sean M J McBride, Catherine H. Choi, Yan Wang, David Liebelt, Evan Braunstein, David Ferreiro, Amita Sehgal, Kathleen K. Siwicki, Thomas C. Dockendorff, Hanh T. Nguyen, Thomas V. McDonald, Thomas A. Jongens

Research output: Contribution to journalArticle

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Abstract

Fragile X syndrome is a leading heritable cause of mental retardation that results from the loss of FMR1 gene function. A Drosophila model for Fragile X syndrome, based on the loss of dfmr1 activity, exhibits phenotypes that bear similarity to Fragile X-related symptoms. Herein, we demonstrate that treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium can rescue courtship and mushroom body defects observed in these flies. Furthermore, we demonstrate that dfmr1 mutants display cognitive deficits in experience-dependent modification of courtship behavior, and treatment with mGluR antagonists or lithium restores these memory defects. These findings implicate enhanced mGluR signaling as the underlying cause of the cognitive, as well as some of the behavioral and neuronal, phenotypes observed in the Drosophila Fragile X model. They also raise the possibility that compounds having similar effects on metabotropic glutamate receptors may ameliorate cognitive and behavioral defects observed in Fragile X patients.

Original languageEnglish (US)
Pages (from-to)753-764
Number of pages12
JournalNeuron
Volume45
Issue number5
DOIs
StatePublished - Mar 3 2005

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Mushroom Bodies
Courtship
Fragile X Syndrome
Metabotropic Glutamate Receptors
Neuronal Plasticity
Drosophila
Pharmacology
Excitatory Amino Acid Antagonists
Lithium
Phenotype
Behavior Therapy
Diptera
Intellectual Disability
Therapeutics
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., ... Jongens, T. A. (2005). Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of Fragile X syndrome. Neuron, 45(5), 753-764. https://doi.org/10.1016/j.neuron.2005.01.038

Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of Fragile X syndrome. / McBride, Sean M J; Choi, Catherine H.; Wang, Yan; Liebelt, David; Braunstein, Evan; Ferreiro, David; Sehgal, Amita; Siwicki, Kathleen K.; Dockendorff, Thomas C.; Nguyen, Hanh T.; McDonald, Thomas V.; Jongens, Thomas A.

In: Neuron, Vol. 45, No. 5, 03.03.2005, p. 753-764.

Research output: Contribution to journalArticle

McBride, SMJ, Choi, CH, Wang, Y, Liebelt, D, Braunstein, E, Ferreiro, D, Sehgal, A, Siwicki, KK, Dockendorff, TC, Nguyen, HT, McDonald, TV & Jongens, TA 2005, 'Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of Fragile X syndrome', Neuron, vol. 45, no. 5, pp. 753-764. https://doi.org/10.1016/j.neuron.2005.01.038
McBride, Sean M J ; Choi, Catherine H. ; Wang, Yan ; Liebelt, David ; Braunstein, Evan ; Ferreiro, David ; Sehgal, Amita ; Siwicki, Kathleen K. ; Dockendorff, Thomas C. ; Nguyen, Hanh T. ; McDonald, Thomas V. ; Jongens, Thomas A. / Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of Fragile X syndrome. In: Neuron. 2005 ; Vol. 45, No. 5. pp. 753-764.
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