Control of Intermale Aggression by Medial Prefrontal Cortex Activation in the Mouse

Abstract

Aggressive behavior is widely observed throughout the animal kingdom because of its adaptiveness for social animals. However, when aggressive behavior exceeds the species-typical level, it is no longer adaptive, so there should be a mechanism to control excessive aggression to keep it within the adaptive range. Using optogenetics, we demonstrate that activation of excitatory neurons in the medial prefrontal cortex (mPFC), but not the orbitofrontal cortex (OFC), inhibits inter-male aggression in mice. At the same time, optogenetic silencing of mPFC neurons causes an escalation of aggressive behavior both quantitatively and qualitatively. Activation of the mPFC suppresses aggressive bursts and reduces the intensity of aggressive behavior, but does not change the duration of the aggressive bursts. Our findings suggest that mPFC activity has an inhibitory role in the initiation and execution, but not the termination, of aggressive behavior, and maintains such behavior within the adaptive range.

Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

“…Aggressive behavior has been linked to PFC hypo-activation, especially in the dorsal anterior cingulate in humans (Sterzer et al 2005; Meyer-Lindenberg and Weinberger 2006), and alcohol further impairs inhibitory control through diminished PFC activity (Anderson et al 2011). Recent studies using optogenetics confirm that the silencing of excitatory neurons in the mPFC causes increased aggressive behavior and its activation suppresses aggression (Takahashi et al 2014). The current experiments showing changes in mPFC glutamate and social behavior are consistent with this body of literature.…”

The neurobiology of offensive aggression: Revealing a modular view

“…Another inhibitory mechanism seems to be provided by the intermediate and ventral regions of the lateral septum (LSi, LSv). The descending fibers from the lateral septal areas precisely traverse the IHA/HAA in a caudal direction [82] and functionally the inhibitory effects on aggression of these brain areas have been observed in many studies, starting with the seminal limbic lesion experiments of the Blanchard's in the late sixties [32,56,[83][84][85]. In addition, the LS is characterized by a sexually dimorphic density of vasopressinergic fibers that originate from the medial amygdala (see also next section below).…”

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex

“…the amygdala, ventral tegmental area, NAc) (Okuyama et al 2016; Wong et al 2016; Lin et al 2011; Hitti & Siegelbaum 2014; Yizhar et al 2011; E. Lee et al 2016; van Kerkhof et al 2013; Takahashi et al 2014; Wang et al 2011; Bicks et al 2015; Gunaydin et al 2014; Felix-Ortiz et al 2016; Amadei et al 2017). …”