EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas.

EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas. Brain Struct Funct. 2020 Sep 25;: Authors: Negwer M, Piera K, Hesen R, Lütje L, Aarts L, Schubert D, Nadif Kasri N 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. PMID: 32975655 [PubMed - as supplied by publisher]
Source: Brain Structure and Function - Category: Neuroscience Authors: Tags: Brain Struct Funct Source Type: research