Abstract
Exposure to a stressor sensitizes or 'primes' the hypothalamic-pituitary-adrenal axis to a subsequent novel stressor. The synaptic mechanisms underlying this priming, however, are not known. We found that exposing a rat to a single stressor primed glutamate synapses in the paraventricular nucleus of the hypothalamus and allowed them to undergo a short-term potentiation (STP) following a burst of high-frequency afferent activity. This transient potentiation requires a corticotrophin-releasing hormone–dependent depression of postsynaptic NMDA receptors (NMDARs). The long-term depression of NMDAR function after stress prevented the vesicular release of an inhibitory retrograde messenger that, in control conditions, arrests STP. Following stress, STP manifested as an increase in the release probability of glutamate that was sufficient to induce multivesicular release. Our findings indicate that the priming of synapses to express STP is a synaptic correlate to stress-induced behavioral and neuroendocrine sensitization.
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Acknowledgements
We thank members of the Bains laboratory and Q.J. Pittman for comments and thoughtful discussion regarding the manuscript. V.M. was supported by a fellowship from the Hotchkiss Brain Institute. J.S.B. is an Alberta Heritage Foundation for Medical Research Senior Scholar. This work was funded by an operating grant from the Canadian Institutes for Health Research.
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J.B.K., V.M. and D.V.B. designed and conducted the experiments and analyzed the data. J.B.K. prepared and wrote the manuscript. J.S.B. designed the experiments, prepared the manuscript and supervised the project.
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Kuzmiski, J., Marty, V., Baimoukhametova, D. et al. Stress-induced priming of glutamate synapses unmasks associative short-term plasticity. Nat Neurosci 13, 1257–1264 (2010). https://doi.org/10.1038/nn.2629
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DOI: https://doi.org/10.1038/nn.2629
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