文章基本信息

标题：Immature Dentate Granule Cells Require Ntrk2/Trkb for the Formation of Functional Hippocampal Circuitry
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作者：Sylvia Badurek ; Marilena Griguoli ; Aman Asif-Malik 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：5
页码：1-43
DOI：10.1016/j.isci.2020.101078
语种：English
出版社：Elsevier
摘要：SummaryEarly in brain development, impaired neuronal signaling during time-sensitive windows triggers the onset of neurodevelopmental disorders. GABA, through its depolarizing and excitatory actions, drives early developmental events including neuronal circuit formation and refinement. BDNF/TrkB signaling cooperates with GABA actions. How these developmental processes influence the formation of neural circuits and affect adult brain function is unknown. Here, we show that early deletion ofNtrk2/Trkbfrom immature mouse hippocampal dentate granule cells (DGCs) affects the integration and maturation of newly formed DGCs in the hippocampal circuitry and drives a premature shift from depolarizing to hyperpolarizing GABAergic actions in the target of DGCs, the CA3 principal cells of the hippocampus, by reducing the expression of the cation-chloride importerNkcc1. These changes lead to the disruption of early synchronized neuronal activity at the network level and impaired morphological maturation of CA3 pyramidal neurons, ultimately contributing to altered adult hippocampal synaptic plasticity and cognitive processes.Graphical AbstractDisplay OmittedHighlights•TrkB signaling shapes hippocampal circuitry by controlling early GABA signaling•AlteredNkcc1expression reduces CA3 pyramidal cell GABAergic excitatory drive•Early network activity is crucial for establishing functional hippocampal circuitryGenetics; Neuroscience