Article | Published:

Social transmission and buffering of synaptic changes after stress

Nature Neurosciencevolume 21pages393403 (2018) | Download Citation


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Denver, R. J. Structural and functional evolution of vertebrate neuroendocrine stress systems. Ann. NY Acad. Sci. 1163, 1–16 (2009).

  2. 2.

    Senst, L., Baimoukhametova, D., Sterley, T.-L. & Bains, J. S. Sexually dimorphic neuronal responses to social isolation. eLife 5, 5904 (2016).

  3. 3.

    Bains, J. S., Wamsteeker Cusulin, J. I. & Inoue, W. Stress-related synaptic plasticity in the hypothalamus. Nat. Rev. Neurosci. 16, 377–388 (2015).

  4. 4.

    Wamsteeker Cusulin, J. I., Füzesi, T., Inoue, W. & Bains, J. S. Glucocorticoid feedback uncovers retrograde opioid signaling at hypothalamic synapses. Nat. Neurosci. 16, 596–604 (2013).

  5. 5.

    Inoue, W. et al. Noradrenaline is a stress-associated metaplastic signal at GABA synapses. Nat. Neurosci. 16, 605–612 (2013).

  6. 6.

    Kuzmiski, J. B., Marty, V., Baimoukhametova, D. V. & Bains, J. S. Stress-induced priming of glutamate synapses unmasks associative short-term plasticity. Nat. Neurosci. 13, 1257–1264 (2010).

  7. 7.

    Zahn-Waxler, C., Radke-Yarrow, M., Wagner, E. & Chapman, M. Development of concern for others. Dev. Psychol. 28, 126–136 (1992).

  8. 8.

    Clay, Z. & de Waal, F. B. M. Bonobos respond to distress in others: consolation across the age spectrum. PLoS One 8, e55206 (2013).

  9. 9.

    Langford, D. J. et al. Social modulation of pain as evidence for empathy in mice. Science 312, 1967–1970 (2006).

  10. 10.

    Ben-Ami Bartal, I., Decety, J. & Mason, P. Empathy and pro-social behavior in rats. Science 334, 1427–1430 (2011).

  11. 11.

    Burkett, J. P. et al. Oxytocin-dependent consolation behavior in rodents. Science 351, 375–378 (2016).

  12. 12.

    Martin, L. J. et al. Reducing social stress elicits emotional contagion of pain in mouse and human strangers. Curr. Biol. 25, 326–332 (2015).

  13. 13.

    Bruchey, A. K., Jones, C. E. & Monfils, M.-H. Fear conditioning by-proxy: social transmission of fear during memory retrieval. Behav. Brain Res. 214, 80–84 (2010).

  14. 14.

    Swanson, L. W. et al. An immunohistochemical study of the organization of catecholaminergic cells and terminal fields in the paraventricular and supraoptic nuclei of the hypothalamus. J. Comp. Neurol. 196, 271–285 (1981).

  15. 15.

    Khan, A. M. et al. MAP kinases couple hindbrain-derived catecholamine signals to hypothalamic adrenocortical control mechanisms during glycemia-related challenges. J. Neurosci. 31, 18479–18491 (2011).

  16. 16.

    Boudaba, C., Schrader, L. A. & Tasker, J. G. Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus. J. Neurophysiol. 77, 3396–3400 (1997).

  17. 17.

    Wamsteeker Cusulin, J. I., Füzesi, T., Watts, A. G. & Bains, J. S. Characterization of corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus of Crh-IRES-Cre mutant mice. PLoS One 8, e64943 (2013).

  18. 18.

    Hennessy, M. B., Kaiser, S. & Sachser, N. Social buffering of the stress response: diversity, mechanisms, and functions. Front. Neuroendocrinol. 30, 470–482 (2009).

  19. 19.

    Knapska, E. et al. Between-subject transfer of emotional information evokes specific pattern of amygdala activation. Proc. Natl. Acad. Sci. USA 103, 3858–3862 (2006).

  20. 20.

    Knapska, E., Mikosz, M., Werka, T. & Maren, S. Social modulation of learning in rats. Learn. Mem. 17, 35–42 (2009).

  21. 21.

    Inagaki, H. et al. The volatility of an alarm pheromone in male rats. Physiol. Behav. 96, 749–752 (2009).

  22. 22.

    Kiyokawa, Y., Kikusui, T., Takeuchi, Y. & Mori, Y. Alarm pheromones with different functions are released from different regions of the body surface of male rats. Chem. Senses 29, 35–40 (2004).

  23. 23.

    Kiyokawa, Y., Kikusui, T., Takeuchi, Y. & Mori, Y. Mapping the neural circuit activated by alarm pheromone perception by c-Fos immunohistochemistry. Brain Res. 1043, 145–154 (2005).

  24. 24.

    Brechbühl, J. et al. Mouse alarm pheromone shares structural similarity with predator scents. Proc. Natl. Acad. Sci. USA 110, 4762–4767 (2013).

  25. 25.

    Kondoh, K. et al. A specific area of olfactory cortex involved in stress hormone responses to predator odours. Nature 532, 103–106 (2016).

  26. 26.

    Füzesi, T., Daviu, N., Wamsteeker Cusulin, J. I., Bonin, R. P. & Bains, J. S. Hypothalamic CRH neurons orchestrate complex behaviours after stress. Nat. Commun. 7, 11937 (2016).

  27. 27.

    Sternson, S. M. Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810–824 (2013).

  28. 28.

    Risbrough, V. B. & Stein, M. B. Role of corticotropin releasing factor in anxiety disorders: a translational research perspective. Horm. Behav. 50, 550–561 (2006).

  29. 29.

    Zhang, R. et al. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice. Mol. Psychiatry 22, 733–744 (2017).

  30. 30.

    Valentino, R. J., Van Bockstaele, E. & Bangasser, D. Sex-specific cell signaling: the corticotropin-releasing factor receptor model. Trends Pharmacol. Sci. 34, 437–444 (2013).

  31. 31.

    Buchanan, T. W., Bagley, S. L., Stansfield, R. B. & Preston, S. D. The empathic, physiological resonance of stress. Soc. Neurosci. 7, 191–201 (2012).

  32. 32.

    Taylor, S. E. et al. Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight. Psychol. Rev. 107, 411–429 (2000).

  33. 33.

    Andari, E. et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci. USA 107, 4389–4394 (2010).

  34. 34.

    Insel, T. R. & Young, L. J. The neurobiology of attachment. Nat. Rev. Neurosci. 2, 129–136 (2001).

  35. 35.

    Jamieson, B.B., Nair, B.B. & Iremonger, K.J. Regulation of hypothalamic CRH neuron excitability by oxytocin. J. Neuroendocrinol. 29, e12532 (2017).

  36. 36.

    Zalaquett, C. & Thiessen, D. The effects of odors from stressed mice on conspecific behavior. Physiol. Behav. 50, 221–227 (1991).

  37. 37.

    Kiyokawa, Y., Shimozuru, M., Kikusui, T., Takeuchi, Y. & Mori, Y. Alarm pheromone increases defensive and risk assessment behaviors in male rats. Physiol. Behav. 87, 383–387 (2006).

  38. 38.

    Grimsley, J. M. S. et al. Contextual modulation of vocal behavior in mouse: newly identified 12 kHz “mid-frequency” vocalization emitted during restraint. Front. Behav. Neurosci. 10, 38 (2016).

  39. 39.

    Mun, H.-S., Lipina, T. V. & Roder, J. C. Ultrasonic vocalizations in mice during exploratory behavior are context-dependent. Front. Behav. Neurosci. 9, 316 (2015).

  40. 40.

    Papes, F., Logan, D. W. & Stowers, L. The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141, 692–703 (2010).

  41. 41.

    Chamero, P., Leinders-Zufall, T. & Zufall, F. From genes to social communication: molecular sensing by the vomeronasal organ. Trends Neurosci. 35, 597–606 (2012).

  42. 42.

    Brechbühl, J., Klaey, M. & Broillet, M.-C. Grueneberg ganglion cells mediate alarm pheromone detection in mice. Science 321, 1092–1095 (2008).

  43. 43.

    Sosulski, D. L., Bloom, M. L., Cutforth, T., Axel, R. & Datta, S. R. Distinct representations of olfactory information in different cortical centres. Nature 472, 213–216 (2011).

  44. 44.

    Pérez-Gómez, A. et al. Innate predator odor aversion driven by parallel olfactory subsystems that converge in the ventromedial hypothalamus. Curr. Biol. 25, 1340–1346 (2015).

  45. 45.

    Berger, J., Heinrichs, M., von Dawans, B., Way, B. M. & Chen, F. S. Cortisol modulates men’s affiliative responses to acute social stress. Psychoneuroendocrinology 63, 1–9 (2016).

  46. 46.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (2013).

Download references


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.

Author information


  1. Hotchkiss Brain Institute and the Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada

    • Toni-Lee Sterley
    • , Dinara Baimoukhametova
    • , Tamás Füzesi
    • , Agnieszka A. Zurek
    • , Nuria Daviu
    • , Neilen P. Rasiah
    • , David Rosenegger
    •  & Jaideep S. Bains


  1. Search for Toni-Lee Sterley in:

  2. Search for Dinara Baimoukhametova in:

  3. Search for Tamás Füzesi in:

  4. Search for Agnieszka A. Zurek in:

  5. Search for Nuria Daviu in:

  6. Search for Neilen P. Rasiah in:

  7. Search for David Rosenegger in:

  8. Search for Jaideep S. Bains in:


T.-L.S. designed and conducted experiments, analyzed the data, and prepared the manuscript. D.B. designed and conducted experiments and assisted with data analyses. T.F. organized viral injections for optogenetic experiments and formatted figures. A.Z., N.D. and N.P. all contributed to electrophysiology data collection. D.R. assisted with organization of optogenetic experiments. J.B. designed experiments, prepared the manuscript, created figures and supervised the project. All of the authors contributed to intellectual discussion and direction of the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jaideep S. Bains.

Supplementary information

About this article

Publication history




Issue Date


Further reading