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

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Reduced gamma oscillations in a mouse model of intellectual disability: a role for impaired repetitive neurotransmission? / Powell, Andrew D.; Saintot, Pierre-philippe; Gill, Kalbinder K.; Bharathan, Ashtami; Buck, S. Caroline; Morris, Gareth; Jiruska, Premysl; Jefferys, John G. R.; Amédée, Thierry (Editor).

In: PLoS ONE, Vol. 9, No. 5, e95871, 06.05.2014.

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Powell, Andrew D. ; Saintot, Pierre-philippe ; Gill, Kalbinder K. ; Bharathan, Ashtami ; Buck, S. Caroline ; Morris, Gareth ; Jiruska, Premysl ; Jefferys, John G. R. ; Amédée, Thierry (Editor). / Reduced gamma oscillations in a mouse model of intellectual disability: a role for impaired repetitive neurotransmission?. In: PLoS ONE. 2014 ; Vol. 9, No. 5.

Bibtex

@article{50aede7e714f4cf3adb53a2cbc89ff3b,
title = "Reduced gamma oscillations in a mouse model of intellectual disability: a role for impaired repetitive neurotransmission?",
abstract = "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.",
keywords = "Disabilities, Gamma spectrometry, Genetic oscillators, Mutation, Neurons, Neurotransmission, Synapses, Vesicles",
author = "Powell, {Andrew D.} and Pierre-philippe Saintot and Gill, {Kalbinder K.} and Ashtami Bharathan and Buck, {S. Caroline} and Gareth Morris and Premysl Jiruska and Jefferys, {John G. R.} and Thierry Am{\'e}d{\'e}e",
year = "2014",
month = may,
day = "6",
doi = "10.1371/journal.pone.0095871",
language = "English",
volume = "9",
journal = "PLoSONE",
issn = "1932-6203",
publisher = "Public Library of Science (PLOS)",
number = "5",

}

RIS

TY - JOUR

T1 - Reduced gamma oscillations in a mouse model of intellectual disability: a role for impaired repetitive neurotransmission?

AU - Powell, Andrew D.

AU - Saintot, Pierre-philippe

AU - Gill, Kalbinder K.

AU - Bharathan, Ashtami

AU - Buck, S. Caroline

AU - Morris, Gareth

AU - Jiruska, Premysl

AU - Jefferys, John G. R.

A2 - Amédée, Thierry

PY - 2014/5/6

Y1 - 2014/5/6

N2 - 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.

AB - 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.

KW - Disabilities

KW - Gamma spectrometry

KW - Genetic oscillators

KW - Mutation

KW - Neurons

KW - Neurotransmission

KW - Synapses

KW - Vesicles

U2 - 10.1371/journal.pone.0095871

DO - 10.1371/journal.pone.0095871

M3 - Article

C2 - 24800744

VL - 9

JO - PLoSONE

JF - PLoSONE

SN - 1932-6203

IS - 5

M1 - e95871

ER -