An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development

Cell Reports
Xinglong GuWei Lu

Abstract

In the mammalian brain, GABAergic synaptic transmission provides inhibitory balance to glutamatergic excitatory drive and controls neuronal output. The molecular mechanisms underlying the development of GABAergic synapses remain largely unclear. Here, we report that NMDA-type ionotropic glutamate receptors (NMDARs) in individual immature neurons are the upstream signaling molecules essential for GABAergic synapse development, which requires signaling via Calmodulin binding motif in the C0 domain of the NMDAR GluN1 subunit. Interestingly, in neurons lacking NMDARs, whereas GABAergic synaptic transmission is strongly reduced, the tonic inhibition mediated by extrasynaptic GABAA receptors is increased, suggesting a compensatory mechanism for the lack of synaptic inhibition. These results demonstrate a crucial role for NMDARs in specifying the development of inhibitory synapses, and suggest an important mechanism for controlling the establishment of the balance between synaptic excitation and inhibition in the developing brain.

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Citations

Oct 26, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mikaela TherrienThomas B Shea
Jan 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Meryl E Horn, Roger A Nicoll
Oct 2, 2020·Physiological Reviews·Rico SchieweckMichael A Kiebler
Oct 20, 2018·Frontiers in Cellular Neuroscience·Liang Zhou, Jingjing Duan
Mar 12, 2020·International Journal of Molecular Sciences·Daniela GandolfiJonathan Mapelli
Mar 7, 2019·Nature Reviews. Neuroscience·Chiayu Q ChiuMichael J Higley
Aug 19, 2020·Molecular Psychiatry·Catharine A MielnikAmy J Ramsey
Feb 7, 2017·Neural Plasticity·Lulu Yao, Qiang Zhou
Jul 19, 2016·Journal of Neurochemistry·Miranda MeleCarlos B Duarte
Jan 19, 2017·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Amir ShojaeiNafiseh Atapour
Oct 21, 2019·Biophysical Journal·Gary J Iacobucci, Gabriela K Popescu
Jun 25, 2020·Developmental Neuroscience·Amita ShresthaOlalekan M Ogundele

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