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

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.

• Authors: Moritz Negwer, Karol Piera, Rick Hesen, Lukas Lütje, Lynn Aarts, Dirk Schubert, Nael Nadif Kasri
• Journal: Brain structure & function (Brain Struct Funct) Vol. 225 Issue 9 Pg. 2701-2716 (Dec 2020) ISSN: 1863-2661 [Electronic] Germany
• PMID: 32975655 (Publication Type: Journal Article)

Chemical References

• Parvalbumins
• GLP protein, mouse
• Histone-Lysine N-Methyltransferase

Topics

• Animals
• Auditory Cortex (growth & development)
• Cerebral Cortex (growth & development)
• Female
• GABAergic Neurons (physiology)
• Histone-Lysine N-Methyltransferase (physiology)
• Interneurons (physiology)
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Parvalbumins (metabolism)
• Somatosensory Cortex (growth & development)
• Visual Cortex (growth & development)