"11130" . "Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?"@en . . . . "1932-6203" . "RIV/00216208:11130/14:10293044" . . "1"^^ . . "Buck, S. Caroline" . "Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?" . . . "hippocampus; vesicle pools; working-memory; cognitive impairment; protein oligophrenin-1; gabaergic transmission; synaptic plasticity; in-vitro; network oscillations; linked mental-retardation"@en . . "Powell, Andrew D." . "5" . "Jiru\u0161ka, P\u0159emysl" . . "Gill, Kalbinder K." . . "9" . . "[95D5C52E8117]" . "http://dx.doi.org/10.1371/journal.pone.0095871" . "Morris, Gareth" . . "Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?"@en . "10.1371/journal.pone.0095871" . "PLoS ONE" . . . . "10"^^ . "RIV/00216208:11130/14:10293044!RIV15-MSM-11130___" . . "Saintot, Pierre-Philippe" . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?" . . "I" . "000338029800036" . . . "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." . "Jefferys, John G. R." . "Bharathan, Ashtami" . "8"^^ . . . "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."@en . "41698" .