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bioRxiv · 10.1101/2021.01.11.426233

Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

You, L.·Cao, J.·Xian, W.·Palihati, M.·Zhu, Y.·Wang, G.·Xie, Y.·Zhou, G.
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Abstract

Intellectual disability is closely related to impaired GABA neurotransmission. Brpf1 was specifically expressed in medial ganglionic eminence (MGE), a developmental niche of GABAergic interneurons, and patients with BRPF1 mutations were mentally retarded. To test its role in development and function of MGE-derived GABAergic interneurons, we performed immunofluorescence staining, whole-cell patch-clamp, MGE transplantation and mRNA-Seq to understand its effect on neuronal differentiation, dendritic morphology, electrophysiology, migration and gene regulation, using mouse MGE-derived GABAergic interneurons infected with AAV-shBrpf1. We found a decreasing trend on parvalbumin+ interneuron differentiation. Moreover, increased firing threshold, decreased number of evoked APs, and a reduced amplitude of mIPSCs were observed before any significant change of MAP2+ dendritic morphology and in vivo migration appeared. Finally, mRNA-Seq analysis revealed that genes related to neurodevelopment and synaptic transmission such as Map2k7 were dysregulated. Our results demonstrated a key role of Brpf1 in inhibitory neurotransmission and related gene expression of GABAergic interneurons.

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You, L., Cao, J., Xian, W., Palihati, M., Zhu, Y., Wang, G., Xie, Y., Zhou, G.. 2021-01-12. Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons. https://doi.org/10.1101/2021.01.11.426233

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