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Stress hormone rapidly tunes synaptic NMDA receptor through membrane dynamics and mineralocorticoid signalling

by Mikasova, Lenka , Kerkhofs, Amber , Krugers, Harm J. , Xiong, Hui , Groc, Laurent , Bouchet, Delphine

in 14 / 14/34 / 631/378/1831 / 631/378/548/1964 / Adaptation / Corticoids / Corticosteroids / Corticosterone / Glutamatergic transmission / Glutamic acid receptors (ionotropic) / Hippocampal plasticity / Hippocampus / Hormones / Humanities and Social Sciences / Interdisciplinary aspects / Membrane trafficking / multidisciplinary / N-Methyl-D-aspartic acid receptors / Neurosciences / Plasma / Potentiation / Science / Science (multidisciplinary) / Signal transduction / Synapses / Synaptic plasticity / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors

2017

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Stress hormone rapidly tunes synaptic NMDA receptor through membrane dynamics and mineralocorticoid signalling

by Mikasova, Lenka , Kerkhofs, Amber , Krugers, Harm J. , Xiong, Hui , Groc, Laurent , Bouchet, Delphine

2017

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Stress hormone rapidly tunes synaptic NMDA receptor through membrane dynamics and mineralocorticoid signalling

by Mikasova, Lenka , Kerkhofs, Amber , Krugers, Harm J. , Xiong, Hui , Groc, Laurent , Bouchet, Delphine

2017

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Journal Article

Stress hormone rapidly tunes synaptic NMDA receptor through membrane dynamics and mineralocorticoid signalling

Mikasova, Lenka,

Kerkhofs, Amber,

Krugers, Harm J.,

Xiong, Hui,

Groc, Laurent,

Bouchet, Delphine

2017

Overview

Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling. Strikingly, extracellular corticosterone was sufficient to increase the trapping of GluN2B-NMDAR within synapses. Functionally, corticosterone-induced potentiation of AMPA receptor content in synapses required the changes in NMDAR surface dynamics. These high-resolution imaging data unveiled that, in hippocampal networks, corticosterone is a natural, potent, fast and specific regulator of GluN2B-NMDAR membrane trafficking, tuning NMDAR-dependent synaptic adaptations.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 14/34