Social buffering in rats reduces fear by oxytocin triggering sustained changes in central amygdala neuronal activity.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
received:
08
07
2021
accepted:
31
01
2024
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
epublish
Résumé
The presence of a companion can reduce fear, but the neural mechanisms underlying this social buffering of fear are incompletely known. We studied social buffering of fear in male and female, and its encoding in the amygdala of male, auditory fear-conditioned rats. Pharmacological, opto,- and/or chemogenetic interventions showed that oxytocin signaling from hypothalamus-to-central amygdala projections underlied fear reduction acutely with a companion and social buffering retention 24 h later without a companion. Single-unit recordings with optetrodes in the central amygdala revealed fear-encoding neurons (showing increased conditioned stimulus-responses after fear conditioning) inhibited by social buffering and blue light-stimulated oxytocinergic hypothalamic projections. Other central amygdala neurons showed baseline activity enhanced by blue light and companion exposure, with increased conditioned stimulus responses that persisted without the companion. Social buffering of fear thus switches the conditioned stimulus from encoding "fear" to "safety" by oxytocin-mediated recruitment of a distinct group of central amygdala "buffer neurons".
Identifiants
pubmed: 38453902
doi: 10.1038/s41467-024-45626-z
pii: 10.1038/s41467-024-45626-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2081Subventions
Organisme : Stiftung Synapsis - Alzheimer Forschung Schweiz AFS (Synapsis Foundation - Alzheimer Research Switzerland)
ID : 2020-PI02
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : IZLSZ3_148803
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : IZLIZ3_200297
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : IZLCZ0_206045
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 31003A_138526
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_192463
Informations de copyright
© 2024. The Author(s).
Références
Ditzen, B. & Heinrichs, M. Psychobiology of social support: the social dimension of stress buffering. Restor. Neurol. Neurosci. 32, 149–162 (2014).
McQuaid, R. J. et al. Relations between plasma oxytocin and cortisol: The stress-buffering role of social support. Neurobiol. Stress 3, 52–60 (2016).
pmcid: 5146198
doi: 10.1016/j.ynstr.2016.01.001
Charuvastra, A. & Cloitre, M. Social bonds and posttraumatic stress disorder. Annu. Rev. Psychol. 59, 301–328 (2008).
pmcid: 2722782
doi: 10.1146/annurev.psych.58.110405.085650
Bowen, A., Shelley, M., Helmes, E. & Landman, M. Disclosure of traumatic experiences, dissociation, and anxiety in group therapy for posttraumatic stress. Anxiety Stress Coping 23, 449–461 (2010).
doi: 10.1080/10615800903414315
Mulej Bratec, S. et al. Your presence soothes me: a neural process model of aversive emotion regulation via social buffering. Soc. Cogn. Affect Neurosci. 15, 561–570 (2020).
pmcid: 7328019
doi: 10.1093/scan/nsaa068
Hennessy, M. B., Kaiser, S. & Sachser, N. Social buffering of the stress response: Diversity, mechanisms, and functions. Front. Neuroendocrinol. 30, 470–482 (2009).
doi: 10.1016/j.yfrne.2009.06.001
Kiyokawa, Y., Kikusui, T., Takeuchi, Y. & Mori, Y. Partner’s stress status influences social buffering effects in rats. Behav. Neurosci. 118, 798–804 (2004).
doi: 10.1037/0735-7044.118.4.798
Kiyokawa, Y., Hiroshima, S., Takeuchi, Y. & Mori, Y. Social buffering reduces male rats’ behavioral and corticosterone responses to a conditioned stimulus. Horm. Behav. 65, 114–118 (2014).
doi: 10.1016/j.yhbeh.2013.12.005
Kiyokawa, Y., Takeuchi, Y. & Mori, Y. Two types of social buffering differentially mitigate conditioned fear responses. Eur. J. Neurosci. 26, 3606–3613 (2007).
doi: 10.1111/j.1460-9568.2007.05969.x
Brill-Maoz, N. & Maroun, M. Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin. Psychoneuroendocrinology 66, 75–81 (2016).
doi: 10.1016/j.psyneuen.2016.01.003
Burkett, J. P. et al. Oxytocin-dependent consolation behavior in rodents. Science 351, 375–378 (2016).
pmcid: 4737486
doi: 10.1126/science.aac4785
Mikami, K., Kiyokawa, Y., Takeuchi, Y. & Mori, Y. Social buffering enhances extinction of conditioned fear responses in male rats. Physiol. Behav. 163, 123–128 (2016).
doi: 10.1016/j.physbeh.2016.05.001
Gutzeit, V. A. et al. Optogenetic reactivation of prefrontal social neural ensembles mimics social buffering of fear. Neuropsychopharmacology 45, 1068–1077 (2020).
pmcid: 7162965
doi: 10.1038/s41386-020-0631-1
Pape, H.-C. & Pare, D. Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol. Rev. 90, 419–463 (2010).
doi: 10.1152/physrev.00037.2009
Leng, G. & Ludwig, M. Neurotransmitters and peptides: whispered secrets and public announcements. J. Physiol. 586, 5625–5632 (2008).
pmcid: 2655398
doi: 10.1113/jphysiol.2008.159103
Ludwig, M. et al. Regulation of activity-dependent dendritic vasopressin release from rat supraoptic neurons. J Physiol 564, 515–522 (2005).
pmcid: 1464450
doi: 10.1113/jphysiol.2005.083931
Landgraf, R. & Neumann, I. D. Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front. Neuroendocrinol. 25, 150–176 (2004).
doi: 10.1016/j.yfrne.2004.05.001
Knobloch, H. S. et al. Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73, 553–566 (2012).
doi: 10.1016/j.neuron.2011.11.030
Bosch, O. J., Meddle, S. L., Beiderbeck, D. I., Douglas, A. J. & Neumann, I. D. Brain oxytocin correlates with maternal aggression: link to anxiety. J. Neurosci. 25, 6807–6815 (2005).
pmcid: 6725361
doi: 10.1523/JNEUROSCI.1342-05.2005
Smith, A. S. & Wang, Z. Hypothalamic oxytocin mediates social buffering of the stress response. Biol. Psychiatry 76, 281–288 (2014).
doi: 10.1016/j.biopsych.2013.09.017
Waldherr, M. & Neumann, I. D. Centrally released oxytocin mediates mating-induced anxiolysis in male rats. Proc. Nat. Acad. Sci. USA 104, 16681–16684 (2007).
pmcid: 2034242
doi: 10.1073/pnas.0705860104
Young, L. J. & Wang, Z. The neurobiology of pair bonding. Nat. Neurosci. 7, 1048–1054 (2004).
doi: 10.1038/nn1327
Lukas, M., Toth, I., Veenema, A. H. & Neumann, I. D. Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics. Psychoneuroendocrinology 38, 916–926 (2013).
doi: 10.1016/j.psyneuen.2012.09.018
Huber, D., Veinante, P. & Stoop, R. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308, 245–248 (2005).
doi: 10.1126/science.1105636
Viviani, D. et al. Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science 333, 104–107 (2011).
doi: 10.1126/science.1201043
Rickenbacher, E., Perry, R. E., Sullivan, R. M. & Moita, M. A. Freezing suppression by oxytocin in central amygdala allows alternate defensive behaviours and mother-pup interactions. eLife 6, e24080 (2017).
pmcid: 5469614
doi: 10.7554/eLife.24080
Arakawa, H., Blanchard, D. C. & Blanchard, R. J. Central oxytocin regulates social familiarity and scent marking behavior that involves amicable odor signals between male mice. Physiol. Behav. 146, 36–46 (2015).
doi: 10.1016/j.physbeh.2015.04.016
Eliava, M. et al. A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing. Neuron 89, 1291–1304 (2016).
pmcid: 5679079
doi: 10.1016/j.neuron.2016.01.041
Alexander, G. M. et al. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron 63, 27–39 (2009).
pmcid: 2751885
doi: 10.1016/j.neuron.2009.06.014
Hasan, M. T. et al. A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System. Neuron 103, 133–146.e8 (2019).
doi: 10.1016/j.neuron.2019.04.029
Ciocchi, S. et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468, 277–282 (2010).
doi: 10.1038/nature09559
Haubensak, W. et al. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270–276 (2010).
pmcid: 3597095
doi: 10.1038/nature09553
Whittle, N. et al. Central amygdala micro-circuits mediate fear extinction. Nat. Commun. 12, 4156 (2021).
pmcid: 8260764
doi: 10.1038/s41467-021-24068-x
Stack, A. et al. Sex differences in social interaction in rats: role of the immediate-early gene zif268. Neuropsychopharmacology 35, 570–580 (2010).
doi: 10.1038/npp.2009.163
McLean, C. P., Asnaani, A., Litz, B. T. & Hofmann, S. G. Gender differences in anxiety disorders: prevalence, course of illness, comorbidity and burden of illness. J. Psychiatr. Res. 45, 1027–1035 (2011).
pmcid: 3135672
doi: 10.1016/j.jpsychires.2011.03.006
Zelikowsky, M., Ding, K. & Anderson, D. J. Neuropeptidergic Control of an Internal Brain State Produced by Prolonged Social Isolation Stress. Cold Spring Harb. Symp. Quant. Biol. 83, 97–103 (2018).
doi: 10.1101/sqb.2018.83.038109
Hersman, S., Allen, D., Hashimoto, M., Brito, S. I. & Anthony, T. E. Stimulus salience determines defensive behaviors elicited by aversively conditioned serial compound auditory stimuli. eLife 9, e53803 (2020).
pmcid: 7190350
doi: 10.7554/eLife.53803
Heffner, H. E. & Heffner, R. S. Hearing Ranges of Laboratory Animals. J. Am. Asso. Lab. Animal Sci. 46, 20–22 (2007).
Walsh, E., Blake, Y., Donati, A., Stoop, R. & von Gunten, A. Early Secure Attachment as a Protective Factor Against Later Cognitive Decline and Dementia. Front. Aging Neurosci. 11, 161 (2019).
pmcid: 6622219
doi: 10.3389/fnagi.2019.00161
Marek, R. & Sah, P. Neural circuits mediating fear learning and extinction. Adv. Neurobiol. 21, 35–48 (2018).
doi: 10.1007/978-3-319-94593-4_2
Shrestha, P. et al. Amygdala inhibitory neurons as loci for translation in emotional memories. Nature 586, 407–411 (2020).
pmcid: 7572709
doi: 10.1038/s41586-020-2793-8
Terburg, D. et al. The basolateral amygdala is essential for rapid escape: A human and rodent study. Cell 175, 723–735.e16 (2018).
pmcid: 6198024
doi: 10.1016/j.cell.2018.09.028
Schiavo, J. K. et al. Innate and plastic mechanisms for maternal behaviour in auditory cortex. Nature 587, 426–431 (2020).
pmcid: 7677212
doi: 10.1038/s41586-020-2807-6
Qian, T. et al. A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments. Nat. Biotechnol. 41, 944–957 (2023).
doi: 10.1038/s41587-022-01561-2
Gorkiewicz, T. et al. Social buffering diminishes fear response but does not equal improved fear extinction. Cereb. Cortex bhac395 https://doi.org/10.1093/cercor/bhac395 . (2022).
Mikami, K., Kiyokawa, Y., Ishii, A. & Takeuchi, Y. Social buffering enhances extinction of conditioned fear responses by reducing corticosterone levels in male rats. Horm. Behav. 118, 104654 (2020).
doi: 10.1016/j.yhbeh.2019.104654
Yu, K. et al. The central amygdala controls learning in the lateral amygdala. Nat. Neurosci. 20, 1680–1685 (2017).
pmcid: 5755715
doi: 10.1038/s41593-017-0009-9
Fuzzo, F. et al. Social buffering suppresses fear-associated activation of the lateral amygdala in male rats: behavioral and neurophysiological evidence. Front. Neurosci. 9, 99 (2015).
pmcid: 4373252
doi: 10.3389/fnins.2015.00099
Kingsbury, L. et al. Correlated neural activity and encoding of behavior across brains of socially interacting animals. Cell 178, 429–446.e16 (2019).
pmcid: 6625832
doi: 10.1016/j.cell.2019.05.022
Guzmán, Y. F. et al. Role of oxytocin receptors in modulation of fear by social memory. Psychopharmacology 231, 2097–2105 (2014).
doi: 10.1007/s00213-013-3356-6
Menon, R. et al. Oxytocin signaling in the lateral septum prevents social fear during lactation. Curr. Biol. 28, 1066–1078.e6 (2018).
doi: 10.1016/j.cub.2018.02.044
Guzmán, Y. F. et al. Fear-enhancing effects of septal oxytocin receptors. Nat. Neurosci. 16, 1185–1187 (2013).
pmcid: 3758455
doi: 10.1038/nn.3465
Ferretti, V. et al. Oxytocin signaling in the central amygdala modulates emotion discrimination in mice. Curr. Biol. 29, 1938–1953.e6 (2019).
doi: 10.1016/j.cub.2019.04.070
Penzo, M. A. et al. The paraventricular thalamus controls a central amygdala fear circuit. Nature 519, 455–459 (2015).
pmcid: 4376633
doi: 10.1038/nature13978
Penha Farias, C. et al. Extinction learning with social support depends on protein synthesis in prefrontal cortex but not hippocampus. Proc. Natl. Acad. Sci. USA 116, 1765–1769 (2019).
pmcid: 6358673
doi: 10.1073/pnas.1815893116
Ferreira, F. F. et al. Social support favors extinction and impairs acquisition of both short- and long-term contextual fear conditioning memory. Neurosci. Lett. 712, 134505 (2019).
doi: 10.1016/j.neulet.2019.134505
Blanchard, R. J., Flannelly, K. J. & Blanchard, D. C. Defensive behavior of laboratory and wild Rattus. norvegicus. J. Comp. Psychol. 100, 101–107 (1986).
doi: 10.1037/0735-7036.100.2.101
Tang, Y. et al. Viral vectors for opto-electrode recording and photometry-based imaging of oxytocin neurons in anesthetized and socially interacting rats. STAR Protocols 3, 101032 (2022).
doi: 10.1016/j.xpro.2021.101032
Grund, T. et al. Chemogenetic activation of oxytocin neurons: Temporal dynamics, hormonal release, and behavioral consequences. Psychoneuroendocrinology 106, 77–84 (2019).
doi: 10.1016/j.psyneuen.2019.03.019
R. Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. (2022).
Hegoburu, C. et al. Dataset of Social buffering switches fear to safety encoding by oxytocin recruitment of central amygdala buffer neurons (Version 1) [Data set]. https://doi.org/10.5281/zenodo.10492711 . (2024).