Potentiation of Divergent Medial Amygdala Pathways Drives Experience-Dependent Aggression Escalation

Jacob C. Nordman, Xiaoyu Ma, Qinhua Gu, Michael Potegal, He Li, Alexxai V. Kravitz, Zheng Li

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Heightened aggression can be serious concerns for the individual and society at large and are symptoms of many psychiatric illnesses, such as post-traumatic stress disorder. The circuit and synaptic mechanisms underlying experience-induced aggression increase, however, are poorly understood. Here we find that prior attack experience leading to an increase in aggressive behavior, known as aggression priming, activates neurons within the posterior ventral segment of the medial amygdala (MeApv). Optogenetic stimulation of MeApv using a synaptic depression protocol suppresses aggression priming, whereas high-frequency stimulation enhances aggression, mimicking attack experience. Interrogation of the underlying neural circuitry revealed that the MeApv mediates aggression priming via synaptic connections with the ventromedial hypothalamus (VmH) and bed nucleus of the stria terminalis (BNST). These pathways undergo NMDAR-dependent synaptic potentiation after attack. Furthermore, we find that the MeApv–VmH synapses selectively control attack duration, whereas the MeApv–BNST synapses modulate attack frequency, both with no effect on social behavior. Synaptic potentiation of the MeApv–VmH and MeApv–BNST pathways contributes to increased aggression induced by traumatic stress, and weakening synaptic transmission at these synapses blocks the effect of traumatic stress on aggression. These results reveal a circuit and synaptic basis for aggression modulation by experience that can be potentially leveraged toward clinical interventions.

Original languageEnglish (US)
Pages (from-to)4858-4880
Number of pages23
JournalJournal of Neuroscience
Volume40
Issue number25
DOIs
StatePublished - Jun 17 2020

Bibliographical note

Funding Information:
Received Feb. 16, 2020; revised Mar. 25, 2020; accepted Apr. 14, 2020. Author contributions: J.C.N., X.M., H.L., A.V.K., and Z.L. designed research; J.C.N. and Q.G. performed research; J.C.N., X.M., and Q.G. analyzed data; J.C.N. wrote the first draft of the paper; J.C.N., M.P., H.L., A.V.K., and Z.L. edited the paper; J.C.N. and Z.L. wrote the manuscript.. This work was supported by National Institute of Mental Health Intramural Research Program 1Z1AMH002881 to Z.L., and National Institute of General Medical Sciences Postdoctoral Research Associate Training Program to J.C.N. We thank Daniel Letchford, Lindsay Ejoh, Princess Miranda, and Winnie Gao for analysis of behavioral and immunohistochemical data. The authors declare no competing financial interests. Correspondence should be addressed to Zheng Li at lizheng2@mail.nih.gov. https://doi.org/10.1523/JNEUROSCI.0370-20.2020 Copyright © 2020 the authors

Publisher Copyright:
Copyright © 2020 the authors

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Aggression
  • Attack experience
  • Medial amygdala
  • Synaptic plasticity
  • Traumatic stress

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