Hypothalamic control of male aggression-seeking behavior

Abstract

In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat provoking cues. While several brain areas have been implicated in generating attack in response to social threat, little is known about the neural mechanisms that promote selfinitiated or "voluntary" aggression seeking when no threat is present. To explore this directly, we utilize an aggression-seeking task wherein male mice can self-initiate aggression trials to gain brief and repeated access to a weaker male that they attack. In males that exhibit rapid task learning, we find that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, is essential for aggression seeking. Using both single unit electrophysiology and population optical recording, we find that VMHvl neurons become active during aggression seeking and their activity tracks changes in task learning and extinction. Inactivation of the VMHvl reduces aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerates moment-to-moment aggression seeking and intensifies future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.Individuals may seek out opportunities to attack, even in the absence of overt threat 1 -9 . In the wild, male mice exhibit stalking behavior if they suspect foreign encroachment 10 , and Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use

Compulsive Addiction-like Aggressive Behavior in Mice

“…Subsequently, Couppis et al (16) and May et al (30) showed that outbred adult male sexually experienced Swiss-Webster resident mice would nose-poke for access to subordinate adult sexually-naïve Swiss-Webster intruders. Most recently, Falkner et al (17) showed that outbred adult male sexually-experienced Swiss Webster resident mice would nose-poke for access to subordinate sexually-naïve inbred Balb/c intruders.…”

“…There is already some evidence for this. Dominant mice will lever press or nose-poke for the opportunity to attack subordinate intruder mice (15–17), as well as form persistent conditioned place preference (CPP) to aggression-paired contexts (18, 19). However, self-administration and CPP are not sufficient to show that a rewarding stimulus is being sought maladaptively, addictively or pathologically (14, 20, 21).…”

An emerging role for the lateral habenula in aggressive behavior

“…For example, dominant male mice will display conditioned-place preference (CPP) for a distinct context previously paired with a novel submissive opponent (Golden et al 2016a, Golden et al 2016b), a phenotype that stably persists for at least eighteen days (Golden et al 2016a). In addition, socially dominant male mice that repeatedly win aggressive contests will learn to perform an operant task (lever press or nose-poke) that will give them access to attack a subordinate intruder (Fish et al 2002, May and Kennedy 2009, Falkner et al 2016), suggesting that aggression in animals can be positively reinforcing in a manner that is analogous to human instrumental aggression-seeking behavior (Elbert et al 2010, Moran et al 2014). Moreover, up to 20% of mice trained in this type of operant paradigm will exhibit “addiction-like” behavior, expending high levels of effort to gain intruder access, demonstrating robust relapse to aggression-seeking, and displaying resistance to punishment-induced suppression of aggression-seeking behavior (Golden et al 2017).…”

Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity

“…Indeed, conspecific aggression can be optogenetically controlled by stimulating or silencing these areas (Falkner and Lin, 2014; Miczek et al, 2015; Unger et al, 2015; Falkner et al, 2016). This neural mechanism is roughly conserved in humans, although the medial prefrontal cortex (mPFC) plays an arguably more prominent role therein (Panksepp, 2011; Yu et al, 2014).…”