EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas
SourceBrain Structure and Function, 225, 9, (2020), pp. 2701-2716
Article / Letter to editor
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Brain Structure and Function
SubjectRadboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience
Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits. Proper development of inhibitory interneurons is crucial for sensory function. Here we report a timeline of Parvalbumin-positive (PV(+)) interneuron development in the three most important sensory cortical areas in the Ehmt1(+/-) mouse. We find a hitherto unreported delay of PV(+) neuron maturation early in sensory development, with layer- and region-specific variability later in development. The delayed PV(+) maturation is also reflected in a delayed maturation of GABAergic transmission in Ehmt1(+/-) auditory cortex, where we find a reduced GABA release probability specifically in putative PV(+) synapses. Together with earlier reports of excitatory impairments in Ehmt1(+/-) neurons, we propose a shift in excitatory-inhibitory balance towards overexcitability in Ehmt1(+/-) sensory cortices as a consequence of early deficits in inhibitory maturation.
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