A central role for anterior cingulate cortex in the control of pathological aggression.

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.
Competing Interests: Declaration of interests J.K.B. was a consultant to/member of advisory board of/and/or speaker for Janssen-Cilag BV, Eli Lilly, Takeda (Shire), Medice, Roche, and Servier. J.C.G. has in the past 4 years been a consultant to Boehringer Ingelheim GmbH. Neither J.K.B. nor J.C.G. are employees of any of these companies, and neither are stock shareholders of any of these companies. The funding organizations or industrial consultancies listed have had no involvement with the conception, design, data analysis and interpretation, review, and/or any other aspects relating to this paper. The remaining authors declare no competing interests.
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