Cortical control of aggression: GABA signalling in the anterior cingulate cortex

Amanda Jager, Houshang Amiri, Natalia Bielczyk, Sabrina van Heukelum, Arend Heerschap, Armaz Aschrafi, Geert Poelmans, Jan K. Buitelaar, Tamas Kozicz, Jeffrey C. Glennon

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Reduced top-down control by cortical areas is assumed to underlie pathological forms of aggression. While the precise underlying molecular mechanisms are still elusive, it seems that balancing the excitatory and inhibitory tones of cortical brain areas has a role in aggression control. The molecular mechanisms underpinning aggression control were examined in the BALB/cJ mouse model. First, these mice were extensively phenotyped for aggression and anxiety in comparison to BALB/cByJ controls. Microarray data was then used to construct a molecular landscape, based on the mRNAs that were differentially expressed in the brains of BALB/cJ mice. Subsequently, we provided corroborating evidence for the key findings from the landscape through 1H-magnetic resonance imaging and quantitative polymerase chain reactions, specifically in the anterior cingulate cortex (ACC). The molecular landscape predicted that altered GABA signalling may underlie the observed increased aggression and anxiety in BALB/cJ mice. This was supported by a 40% reduction of 1H-MRS GABA levels and a 20-fold increase of the GABA-degrading enzyme Abat in the ventral ACC. As a possible compensation, Kcc2, a potassium-chloride channel involved in GABA-A receptor signalling, was found increased. Moreover, we observed aggressive behaviour that could be linked to altered expression of neuroligin-2, a membrane-bound cell adhesion protein that mediates synaptogenesis of mainly inhibitory synapses. In conclusion, Abat and Kcc2 seem to be involved in modulating aggressive and anxious behaviours observed in BALB/cJ mice through affecting GABA signalling in the ACC.

Original languageEnglish (US)
Pages (from-to)5-16
Number of pages12
JournalEuropean Neuropsychopharmacology
Volume30
DOIs
StatePublished - Jan 2020

Keywords

  • Aggression
  • Gyrus Cinguli
  • Magnetic resonance spectroscopy
  • Mice
  • Translational medical research

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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    Jager, A., Amiri, H., Bielczyk, N., van Heukelum, S., Heerschap, A., Aschrafi, A., Poelmans, G., Buitelaar, J. K., Kozicz, T., & Glennon, J. C. (2020). Cortical control of aggression: GABA signalling in the anterior cingulate cortex. European Neuropsychopharmacology, 30, 5-16. https://doi.org/10.1016/j.euroneuro.2017.12.007