Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Martin
Stéphane
S
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol, United Kingdom.
Henley
Jeremy M
JM
Holman
David
D
Zhou
Ming
M
Wiegert
Olof
O
van Spronsen
Myrrhe
M
Joëls
Marian
M
Hoogenraad
Casper C
CC
Krugers
Harmen J
HJ
D033962:Adaptor Protein Complex 2 / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology*; D004594:Electrophysiology; D004705:Endocytosis / Q000187:drug effects; D036681:Fluorescence Recovery After Photobleaching; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D033962:Adaptor Protein Complex 2; D000893:Anti-Inflammatory Agents; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D016202:N-Methylaspartate; D003345:Corticosterone