UvA-DARE ( Digital Academic Repository ) 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. Methodology/Principal Findings: 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. Conclusion/Significance: 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. Citation: Martin S, Henley JM, Holman D, Zhou M, Wiegert O, et al. (2009) Corticosterone Alters AMPAR Mobility and Facilitates Bidirectional Synaptic Plasticity. PLoS ONE 4(3): e4714. doi:10.1371/journal.pone. 0004714 Editor: Georges Chapouthier, L’université Pierre et Marie Curie, France Received January 14, 2009; Accepted January 21, 2009; Published March 5, 2009 Copyright: 2009 Martin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: We thank Dr. Morgan Sheng for GluR1-2 C-terminal antibodies and useful comments, Nanda Keijzer, Yasuko Nakamura and Samantha Spangler for preparing hippocampal cultures. This work was supported by grants from the EU (GRIPPANT, PL 005320), the MRC and the Wellcome Trust to JMH; the Netherlands Organization for Scientific Research (NWO Cognition program 051.02.010 to H.K. and NWO-ZonMw-VIDI award to C.C.H); the Dutch Brain foundation (13F05(2) to H.K. ); the Royal Dutch Academy of Arts and Sciences (05CDP013) to H.K. and M.Z. , the Human Frontier Science Program Career Development Award (HFSP-CDA to C.C.H) and the European Science Foundation European Young Investigators award (ESF-EURYI to C.C.H). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: c.hoogenraad@erasmusmc.nl (CCH); h.krugers@uva.nl (HJK) ¤ Current address: IN2M / IPMC, CNRS, Valbonne, France . These authors contributed equally to this work.