Citation

van Heukelum S, Tulva K, Geers FE, van Dulm S, Ruisch IH, Mill J, Viana JF, Beckmann CF, Buitelaar JK, Poelmans G, Glennon JC, Vogt BA, Havenith MN, França ASC. Curr. Biol. 2021; ePub(ePub): ePub.

Copyright

(Copyright © 2021, Elsevier Publishing)

DOI

10.1016/j.cub.2021.03.062

PMID

unavailable

Abstract

Controlling aggression is a crucial skill in social species like rodents and humans and has been associated with anterior cingulate cortex (ACC). Here, we directly link the failed regulation of aggression in BALB/cJ mice to ACC hypofunction. We first show that ACC in BALB/cJ mice is structurally degraded: neuron density is decreased, with pervasive neuron death and reactive astroglia. Gene-set enrichment analysis suggested that this process is driven by neuronal degeneration, which then triggers toxic astrogliosis. cFos expression across ACC indicated functional consequences: during aggressive encounters, ACC was engaged in control mice, but not BALB/cJ mice. Chemogenetically activating ACC during aggressive encounters drastically suppressed pathological aggression but left species-typical aggression intact. The network effects of our chemogenetic perturbation suggest that this behavioral rescue is mediated by suppression of amygdala and hypothalamus and activation of mediodorsal thalamus. Together, these findings highlight the central role of ACC in curbing pathological aggression.

Language: en

Keywords

aggression; astrogliosis; BALB strain; chemogenetics; cingulate cortex; mouse model; neuron death; resident-intruder test; rodent