Abstract
Exposure to a stressor sensitizes behavioral and hormonal responses to future stressors. Stress-associated release of noradrenaline enhances the capacity of central synapses to show plasticity (metaplasticity). We found noradrenaline-dependent metaplasticity at GABA synapses in the paraventricular nucleus of the hypothalamus in rat and mouse that controls the hypothalamic-pituitary-adrenal axis. In vivo stress exposure was required for these synapses to undergo activity-dependent long-term potentiation (LTPGABA). The activation of β-adrenergic receptors during stress functionally upregulated metabotropic glutamate receptor 1 (mGluR1), allowing for mGluR1-dependent LTPGABA during afferent bursts. LTPGABA was expressed postsynaptically and manifested as the emergence of new functional synapses. Our findings provide, to the best of our knowledge, the first demonstration that noradrenaline release during an in vivo challenge alters information storage capacity at GABA synapses. Because these GABA synapses become excitatory following acute stress, this metaplasticity may contribute to neuroendocrine sensitization to stress.
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Change history
14 April 2013
In the version of this article initially published online, the trace in Figure 4a was labeled DHPG. It should have been labeled MCPG. Also, text duplicating the n-value specifications from the Figure 1e legend was inserted into the Figure 1a image. The errors have been corrected for the print, PDF and HTML versions of this article.
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Acknowledgements
We thank members of the Bains laboratory for comments and discussion regarding the manuscript and C. Sank for technical assistance. We are grateful to the Hotchkiss Brain Institute for providing optogenetics core resources. AAV vectors carrying the ChR2 gene were developed by K. Deisseroth (Stanford University) and distributed by Addgene. W.I. and T.F. are supported by a postdoctoral fellowship, and J.I.W.C. and K.K. by a PhD scholarship from the Alberta Innovates–Health Solutions (AI-HS). W.I., K.K. and J.I.W.C. also received fellowship and/or scholarship support from the Hotchkiss Brain Institute. J.S.B. and P.J.W. are AI-HS Senior Scholars. Q.J.P. is an AI-HS Scientist. This work was funded by operating grants from the Canadian Institute for Health Research (J.S.B., P.J.W. and Q.J.P.).
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W.I. designed and conducted the experiments, analyzed the data, and prepared and wrote the manuscript. D.V.B., T.F. and J.I.W.C. designed and conducted the experiments and analyzed the data. T.F., K.K. and P.J.W. developed AAV-ChR2 and Th-Cre mouse tools. Q.J.P. supervised the project and edited the manuscript. J.S.B. designed the experiments, prepared the manuscript and supervised the project.
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Inoue, W., Baimoukhametova, D., Füzesi, T. et al. Noradrenaline is a stress-associated metaplastic signal at GABA synapses. Nat Neurosci 16, 605–612 (2013). https://doi.org/10.1038/nn.3373
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DOI: https://doi.org/10.1038/nn.3373
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