Stress can trigger enduring changes in neural circuits and synapses. The behavioral and hormonal consequences of stress can also be transmitted to others, but whether this transmitted stress has similar effects on synapses is not known. We found that authentic stress and transmitted stress in mice primed paraventricular nucleus of the hypothalamus (PVN) corticotropin-releasing hormone (CRH) neurons, enabling the induction of metaplasticity at glutamate synapses. In female mice that were subjected to authentic stress, this metaplasticity was diminished following interactions with a naive partner. Transmission from the stressed subject to the naive partner required the activation of PVN CRH neurons in both subject and partner to drive and detect the release of a putative alarm pheromone from the stressed mouse. Finally, metaplasticity could be transmitted sequentially from the stressed subject to multiple partners. Our findings demonstrate that transmitted stress has the same lasting effects on glutamate synapses as authentic stress and reveal an unexpected role for PVN CRH neurons in transmitting distress signals among individuals.
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We thank C. Breiteneder, M. Tsutsui and R. Barasi for technical assistance with tissue processing, injections and mouse colony maintenance. We thank K. Gorzo for assisting with behavioral analysis and R.P. Bonin (University of Toronto) for providing us with the original macro for analyzing behaviors. We thank K. Deisseroth (Stanford University) for kindly providing the viral constructs used for optical silencing of CRH neurons. We are grateful for the support of the Hotchkiss Brain Institute in creating the HBI Advance Light and Optogenetics core facility. This research was funded by operating grants to J.S.B. from the Canadian Institutes for Health Research (CIHR 86501) and Brain Canada Multi-Investigator Research Initiative and the Brain Canada Neurophotonics Platform. T.-L.S. and N.D. are supported by Fellowships from Alberta Innovates-Health Solutions (AIHS) and the UCalgary Eyes High Program. A.Z. is a CIHR Banting Fellow with additional support from AIHS.
The authors declare no competing financial interests.
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Sterley, TL., Baimoukhametova, D., Füzesi, T. et al. Social transmission and buffering of synaptic changes after stress. Nat Neurosci 21, 393–403 (2018). https://doi.org/10.1038/s41593-017-0044-6