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

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381 Scopus citations

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

ASJC Scopus subject areas

  • Neuroscience(all)

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    McBride, S. M. J., Choi, C. H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., Sehgal, A., Siwicki, K. K., Dockendorff, T. C., Nguyen, H. T., McDonald, T. V., & 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