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- Title
Defiiciency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission in MGE-derived GABAergic interneurons.
- Authors
Jingli Cao; Weiwei Xian; Palihati, Maierdan; Yu Zhu; Guoxiang Wang; Yunli Xie; Guomin Zhou; Linya You
- 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 showed intellectual disability. To test its role in the 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 mouseMGE-derived GABAergic interneurons infected with AAV-shBrpf1. The results showed that Brpf1 knockdown had a decreasing trend, although not significant, on the differentiation of GABAergic interneurons into parvalbumin+ interneurons. Moreover, increased firing threshold, decreased number of evoked action potentials, and a reduced amplitude of miniature inhibitory postsynaptic currents were observed before any significant change of MAP2+ dendritic morphology and in vivo migration ability 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.
- Subjects
INTERNEURONS; NEURAL transmission; EVOKED potentials (Electrophysiology); NEURONAL differentiation; GENETIC regulation; INTELLECTUAL disabilities
- Publication
G3: Genes | Genomes | Genetics, 2021, Vol 11, Issue 8, p1
- ISSN
2160-1836
- Publication type
Article
- DOI
10.1093/g3journal/jkab090