Ventromedial Hypothalamus and the Generation of Aggression

Abstract

Aggression is a costly behavior, sometimes with severe consequences including death. Yet aggression is prevalent across animal species ranging from insects to humans, demonstrating its essential role in the survival of individuals and groups. The question of how the brain decides when to generate this costly behavior has intrigued neuroscientists for over a century and has led to the identification of relevant neural substrates. Various lesion and electric stimulation experiments have revealed that the hypothalamus, an ancient structure situated deep in the brain, is essential for expressing aggressive behaviors. More recently, studies using precise circuit manipulation tools have identified a small subnucleus in the medial hypothalamus, the ventrolateral part of the ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression and aggression-seeking behaviors. Here, we provide an updated summary of the evidence that supports a role of the VMHvl in aggressive behaviors. We will consider our recent findings detailing the physiological response properties of populations of VMHvl cells during aggressive behaviors and provide new understanding regarding the role of the VMHvl embedded within the larger whole-brain circuit for social sensation and action.

Keywords: VMHvl; aggression; mouse; neural activity; neuromodulation.

Figure 1

Self-initiated aggression seeking task is utilized to study appetitive phase of aggression. Schematic illustration of the self-initiated aggression seeking task. By poking the social poke, subjects gain access to a submissive intruder and attack.

Figure 2

The activity of VMHvl increases during social investigation, aggression seeking and attack, and when the animal is at a heightened aggressive state.

Figure 3

Circuit mechanisms underlying VMHvl activity change during agonistic encounters. (A) The neural circuits upstream of the VMHvl that relay olfactory information. (B) Neuromodulators, neuropeptides, and neurosteroids that could potentially generate increased spontaneous activity in the VMHvl and cause sustained aggressive state. (C) Schematics illustrating a model responsible for activity increase at the VMHvl during attack initiation. In the model, inputs from the upstream regions bring the VMHvl activity to a threshold and then the recurrent excitatory network within the VMHvl quickly amplifies the signal to initiate attack and maintain it throughout the attack. OE, olfactory epithelium; VNO, vomeronasal organ; MOB, main olfactory bulb; AOB, accessory olfactory bulb; BNST, bed nucleus of stria terminalis; MEA, medial amygdala; plCOA, posterolateral cortical amygdala; PMv, ventral premammillary nucleus; VMHvl, ventromedial hypothalamus ventrolateral part. LHAjvv, lateral hypothalamic area, juxtaventromedial region, ventral zone; TU, tuberal nucleus; LS, lateral septum; BMAp, posterior basomedial nucleus; PA, posterior amygdala; SUBv, ventral subiculum.

Figure 4

The potential pathways for “bottom up” modulation. (Left) the key relays to transfer hunger state related information from AGRP neurons to the insular cortex; (Right) a putative pathway that transfers aggressive state related information from the VMHvl to the prefrontal cortex. InsCox, insular cortex; BMA, basomedial amygdala; PVT, paraventricular nucleus of thalamus; AgRP, agouti-related peptide in the arcuate nucleus; PFC, prefrontal cortex; VMHvl, ventromedial hypothalamus ventrolateral part.