Structural Degradation in Midcingulate Cortex Is Associated with Pathological Aggression in Mice

Abstract

Pathological aggression is a debilitating feature of many neuropsychiatric disorders, and cingulate cortex is one of the brain areas centrally implicated in its control. Here we explore the specific role of midcingulate cortex (MCC) in the development of pathological aggression. To this end, we investigated the structural and functional degeneration of MCC in the BALB/cJ strain, a mouse model for pathological aggression. Compared to control animals from the BALB/cByJ strain, BALB/cJ mice expressed consistently heightened levels of aggression, as assessed by the resident-intruder test. At the same time, immunohistochemistry demonstrated stark structural degradation in the MCC of aggressive BALB/cJ mice: Decreased neuron density and widespread neuron death were accompanied by increased microglia and astroglia concentrations and reactive astrogliosis. cFos staining indicated that this degradation had functional consequences: MCC activity did not differ between BALB/cJ and BALB/cByJ mice at baseline, but unlike BALB/cByJ mice, BALB/cJ mice failed to activate MCC during resident-intruder encounters. This suggests that structural and functional impairments of MCC, triggered by neuronal degeneration, may be one of the drivers of pathological aggression in mice, highlighting MCC as a potential key area for pathologies of aggression in humans.

Whole-brain analysis of CO2chemosensitive regions and identification of the retrotrapezoid and medullary raphé nuclei in the common marmoset (Callithrix jacchus)

“…Two anti-c-fos antibodies were used to validate specificity of c-fos staining in the adult marmoset (see Table 1). These antibodies have previously been successfully used as a marker for neuronal activity in rodent, non-human primate, and human tissue (Sarkar et al 2021; Heukelum et al 2021; Lopez et al 2014). The polyclonal guinea pig anti-cFps antibody (1:250, Synaptic Systems, catalog #226004, RRID: AB_2619946) has a synthetic peptide corresponding to amino acids 2 to 17 of rat c-fos.…”

Dimensions of Pathological Aggression: From Neurobiology to Therapy

“…The final paper of this set of studies looked at a model for pathological aggression investigating the association of aggression with structural and functional degeneration in mice. Van Heukelum and colleagues showed that the midcingulate cortex was not activated during a resident-intruder test after massive structural degeneration [6]. Observing heightened levels of aggression in these mice, the authors highlighted the midcingulate cortex as a potential key area for pathological aggression.…”