Fragile X mental retardation protein knockdown in the developing Xenopus tadpole optic tectum results in enhanced feedforward inhibition and behavioral deficits

Neural Dev. 2016 Aug 8;11(1):14. doi: 10.1186/s13064-016-0069-7.


Background: Fragile X Syndrome is the leading monogenetic cause of autism and most common form of intellectual disability. Previous studies have implicated changes in dendritic spine architecture as the primary result of loss of Fragile X Mental Retardation Protein (FMRP), but recent work has shown that neural proliferation is decreased and cell death is increased with either loss of FMRP or overexpression of FMRP. The purpose of this study was to investigate the effects of loss of FMRP on behavior and cellular activity.

Methods: We knocked down FMRP expression using morpholino oligos in the optic tectum of Xenopus laevis tadpoles and performed a series of behavioral and electrophysiological assays. We investigated visually guided collision avoidance, schooling, and seizure propensity. Using single cell electrophysiology, we assessed intrinsic excitability and synaptic connectivity of tectal neurons.

Results: We found that FMRP knockdown results in decreased swimming speed, reduced schooling behavior and decreased seizure severity. In single cells, we found increased inhibition relative to excitation in response to sensory input.

Conclusions: Our results indicate that the electrophysiological development of single cells in the absence of FMRP is largely unaffected despite the large neural proliferation defect. The changes in behavior are consistent with an increase in inhibition, which could be due to either changes in cell number or altered inhibitory drive, and indicate that FMRP can play a significant role in neural development much earlier than previously thought.

Keywords: FMRP; Fragile X Mental Retardation Protein; Fragile X syndrome; Xenopus laevis; inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal*
  • Escape Reaction / physiology
  • Excitatory Postsynaptic Potentials
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / physiology*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / physiopathology*
  • Gene Knockdown Techniques
  • Membrane Potentials
  • Neural Inhibition*
  • Neurons / metabolism
  • Neurons / physiology*
  • Seizures / genetics
  • Superior Colliculi / metabolism
  • Superior Colliculi / physiology*
  • Swimming / physiology
  • Xenopus laevis


  • Fragile X Mental Retardation Protein