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.
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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)
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Chemical References |
- Parvalbumins
- GLP protein, mouse
- Histone-Lysine N-Methyltransferase
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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)
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