Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity

• Published in: PloS one Vol. 4; no. 3; p. e4714
• Main Authors: Martin, Stéphane, Henley, Jeremy M, Holman, David, Zhou, Ming, Wiegert, Olof, van Spronsen, Myrrhe, Joëls, Marian, Hoogenraad, Casper C, Krugers, Harmen J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-03-2009; Public Library of Science (PLoS)
• Subjects: Adaptor Protein Complex 2; Adaptor Protein Complex 2 - metabolism; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents - pharmacology; Biochemistry, Molecular Biology; Cellular Biology; Corticosteroids; Corticosterone; Corticosterone - pharmacology; Diffusion; Electrophysiology; Endocytosis; Endocytosis - drug effects; Fluorescence Recovery After Photobleaching; Gene expression; Glucocorticoids; Glutamic acid receptors; Hippocampal plasticity; Hippocampus; Hippocampus - cytology; Hippocampus - physiology; Hormones; Imaging techniques; Immunocytochemistry; Immunoglobulins; Lateral diffusion; Learning; Life Sciences; Memory; N-Methyl-D-aspartic acid receptors; N-Methylaspartate; N-Methylaspartate - metabolism; Neuronal Plasticity; Neuronal Plasticity - drug effects; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neurons and Cognition; Neuroscience/Animal Cognition; Neuroscience/Behavioral Neuroscience; Neuroscience/Neuronal Signaling Mechanisms; Neurosciences; Plasticity; Protein biosynthesis; Protein synthesis; Rats; Receptors; Receptors, AMPA; Receptors, AMPA - metabolism; Receptors, Glucocorticoid; Receptors, Glucocorticoid - metabolism; Recovery (Medical); Rodents; Steroids (Organic compounds); Synaptic plasticity; Synaptic strength; Synaptic Transmission; Synaptic Transmission - drug effects; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004714

The stress hormone corticosterone has the ability both to enhance and suppress synaptic plasticity and learning and memory processes. However, until today there is very little known about the molecular mechanism that underlies the bidirectional effects of stress and corticosteroid hormones on synaptic efficacy and learning and memory processes. In this study we investigate the relationship between corticosterone and AMPA receptors which play a critical role in activity-dependent plasticity and hippocampal-dependent learning.
Using immunocytochemistry and live cell imaging techniques we show that corticosterone selectively increases surface expression of the AMPAR subunit GluR2 in primary hippocampal cultures via a glucocorticoid receptor and protein synthesis dependent mechanism. In agreement, we report that corticosterone also dramatically increases the fraction of surface expressed GluR2 that undergo lateral diffusion. Furthermore, our data indicate that corticosterone facilitates NMDAR-invoked endocytosis of both synaptic and extra-synaptic GluR2 under conditions that weaken synaptic transmission.
Our results reveal that corticosterone increases mobile GluR2 containing AMPARs. The enhanced lateral diffusion properties can both facilitate the recruitment of AMPARs but under appropriate conditions facilitate the loss of synaptic AMPARs (LTD). These actions may underlie both the facilitating and suppressive effects of corticosteroid hormones on synaptic plasticity and learning and memory and suggest that these hormones accentuate synaptic efficacy.