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

Research output: Contribution to journalArticlepeer-review


  • Pierre-philippe Saintot
  • Kalbinder K. Gill
  • Ashtami Bharathan
  • S. Caroline Buck
  • Gareth Morris
  • Thierry Amédée (Editor)

Colleges, School and Institutes


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