1. EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas.
- Author
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Negwer, Moritz, Piera, Karol, Hesen, Rick, Lütje, Lukas, Aarts, Lynn, Schubert, Dirk, and Nadif Kasri, Nael
- Subjects
AUDITORY cortex ,SENSORIMOTOR integration ,INTELLECTUAL disabilities ,INTERNEURONS ,METHYLTRANSFERASES - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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