Reduced gamma oscillations in a mouse model of intellectual disability: a role for impaired repetitive neurotransmission?

Andrew D. Powell, Pierre-philippe Saintot, Kalbinder K. Gill, Ashtami Bharathan, S. Caroline Buck, Gareth Morris, Premysl Jiruska, John G. R. Jefferys, Thierry Amédée (Editor)

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5 Citations (Scopus)
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Intellectual disability affects 2–3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals.
Original languageEnglish
Article numbere95871
JournalPLoS ONE
Issue number5
Publication statusPublished - 6 May 2014


  • Disabilities
  • Gamma spectrometry
  • Genetic oscillators
  • Mutation
  • Neurons
  • Neurotransmission
  • Synapses
  • Vesicles


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