TY - JOUR
T1 - Immature Dentate Granule Cells Require Ntrk2/Trkb for the Formation of Functional Hippocampal Circuitry
AU - Badurek, Sylvia
AU - Griguoli, Marilena
AU - Asif-Malik, Aman
AU - Zonta, Barbara
AU - Guo, Fei
AU - Middei, Silvia
AU - Lagostena, Laura
AU - Jurado-Parras, Maria Teresa
AU - Gillingwater, Thomas H.
AU - Gruart, Agnès
AU - Delgado-García, José María
AU - Cherubini, Enrico
AU - Minichiello, Liliana
PY - 2020/5/22
Y1 - 2020/5/22
N2 - 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.
AB - 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.
U2 - 10.1016/j.isci.2020.101078
DO - 10.1016/j.isci.2020.101078
M3 - Article
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 5
M1 - 101078
ER -