Immature Dentate Granule Cells Require Ntrk2/Trkb for the Formation of Functional Hippocampal Circuitry

Sylvia Badurek, Marilena Griguoli, Aman Asif-Malik, Barbara Zonta, Fei Guo, Silvia Middei, Laura Lagostena, Maria Teresa Jurado-Parras, Thomas H. Gillingwater, Agnès Gruart, José María Delgado-García, Enrico Cherubini, Liliana Minichiello

Research output: Contribution to JournalArticlepeer-review

Abstract

Early 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 of Ntrk2/Trkb from 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 importer Nkcc1. 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.
Original languageEnglish
Article number101078
Number of pages43
JournaliScience
Volume23
Issue number5
Early online date17 Apr 2020
DOIs
Publication statusPublished - 22 May 2020

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