TY - JOUR
T1 - Cortical control of aggression
T2 - GABA signalling in the anterior cingulate cortex
AU - Jager, Amanda
AU - Amiri, Houshang
AU - Bielczyk, Natalia
AU - van Heukelum, Sabrina
AU - Heerschap, Arend
AU - Aschrafi, Armaz
AU - Poelmans, Geert
AU - Buitelaar, Jan K.
AU - Kozicz, Tamas
AU - Glennon, Jeffrey C.
N1 - Publisher Copyright:
© 2017 Elsevier B.V. and ECNP
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Aggression
KW - Gyrus Cinguli
KW - Magnetic resonance spectroscopy
KW - Mice
KW - Translational medical research
UR - http://www.scopus.com/inward/record.url?scp=85038970134&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038970134&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2017.12.007
DO - 10.1016/j.euroneuro.2017.12.007
M3 - Article
C2 - 29274996
AN - SCOPUS:85038970134
SN - 0924-977X
VL - 30
SP - 5
EP - 16
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -