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Aggression - The Ventromedial Hypothalamus And Aggression Generation

Aggression is a behavior that may sometimes have fatal consequences. But aggression is a trait shared by all animal species, from insects to humans. This shows how important it is to both the survival of the individual and the survival of the group.

Neuroscientists have been curious in how the brain chooses when to produce this expensive activity for more than a century, and this curiosity has resulted in the discovery of pertinent neural substrates.

According to several lesion and electric stimulation investigations, the ancient region located deep inside the brain known as the hypothalamus is crucial for expressing aggressive behaviors.

Studies that used precise circuit modification techniques found that the ventrolateral section of the ventromedial hypothalamus (VMHvl), a small subnucleus in the medial hypothalamus, is a key part of both aggressive and aggression-seeking behavior.

Here, we give a fresh look at the evidence that the VMHvl is involved in aggressive behavior.

We talked about the specific physiological characteristics of VMHvl cell populations during aggressive behavior as well as recent findings about the function of VMHvl cells embedded in the larger whole-brain circuit for social action and sensation.

What Is Aggression?

The word "aggression" in psychology refers to a variety of actions that might cause bodily and psychological damage to you, other people, or inanimate objects in the environment. A person's bodily or emotional harm to another is at the heart of aggression. While everyone experiences some aggression, when it becomes intense or pervasive, it might be an indication of a mental health problem, a drug use disorder, or another health problem.

Aggression may be used for a variety of goals, such as:

  • Expressing hatred or rage
  • Asserting one's power
  • Frightening or intimidating
  • Getting a goal done
  • Fear-induced possession expression
  • In response to pain
  • Rivalry with others

What Are Some Types Of Aggression?

Aggression is divided into two primary categories by psychologists. Whether one is the attacker or the target, both have negative effects on the people who are involved.

Impulsive Aggression

Impulsive aggression, sometimes referred to as emotional or reactive violence, is characterized by intense emotions. Impulsive aggression, particularly when brought on by anger, activates the brain's acute danger response system, which involves the periaqueductal gray, amygdala, and hypothalamus.

This kind of violence is unintentional and often occurs in the heat of the moment. If a car cuts you off in traffic and you start swearing and yelling at the other driver, you are being impulsively aggressive.

Instrumental Aggression

Instrumental aggression, sometimes referred to as predatory aggression, is characterized by actions meant to further a wider objective. A means to an aim, instrumental hostility is often meticulously planned.

This kind of aggressiveness includes hurting a victim during a robbery. The aggressor's goal is to obtain money, and inflicting harm on another person is a means to that end.

What Are Causes Of Aggression?

What triggers excessive or inappropriate aggressiveness is unknown. It's probable that a number of variables are at play, such as a person's biology, environment, and psychological background.

Biological Factors

Aggression may be influenced by hormonal and genetic variables. Aggression may be associated with imbalances in a number of hormones, including cortisol and testosterone, as well as neurotransmitters, including serotonin and dopamine. Genetics is only one of the many causes of these abnormalities.

Aggression may also be influenced by brain shape. Aggressive behavior is more common in those with structural amygdala abnormalities than in their counterparts. Aggressive behavior may also be influenced by alterations in other parts of the brain.

Environmental Factors

Whether or not you display aggressive behavior may depend on your upbringing. Children who encounter hostility as they grow up may be more inclined to think that violence and hostility are acceptable social behaviors. Trauma suffered as a youngster may also influence an adult's violent conduct.

Childhood Trauma And Intermittent Explosive Disorder

The well-known Bobo doll experiment by psychologist Albert Bandura showed that observational learning may also contribute to the emergence of violence. Children in this study were more likely to emulate an adult model's hostile behavior towards a Bobo doll after seeing a video clip of the behavior.

Psychological Factors

Aggressive conduct may be linked to a number of mental health disorders, including:

  • Attention-deficit/hyperactivity disorder (ADHD)
  • Bipolar disorder
  • Borderline personality disorder (BPD)
  • Narcissism
  • Post-traumatic stress disorder (PTSD)

Aggression may also be influenced by epilepsy, dementia, psychosis, drug use disorders, and anomalies or lesions to the brain.

An Essential Role For The VMHvl In Aggressive Behaviors

Aggression is needed for resource competition, settling disputes, defense, and protecting relatives. Electrical stimulation experiments in cats, rats, chickens, and primates have shown the medial hypothalamus has a role in aggressive behavior.

Recent research in mice utilizing more precise functional manipulation methods identified the ventrolateral section of the ventromedial hypothalamus (VMHvl) as a crucial area to generate inter-male aggression.

Silencing this area stops fights between men, while activating the VMHvl with optogenetics but not the areas around it makes people more likely to attack less-than-ideal targets, like women and inanimate objects.

Hormone receptors, such as estrogen receptor alpha (Esr1) and progesterone receptor (PR), are abundant in the VMHvl. Several studies have shown that cells that make hormone receptors are very important in both male and female aggression.Killing PR+ or Esr1+ cells reduces aggression.

Optogenetic activation of VMHvl Esr1+ cells evoked instantaneous attack, but pharmacogenetic activation of PR+ cells enhanced attack frequency. Activating VMHvl PR+ cells also made castrated males and males with bad olfactory inputs more aggressive, showing that VMHvl activation can "override" hormones and senses that are usually needed for aggression to happen.

The VMHvl is the most understood aggression-related brain circuit due to our identification of neuronal response features during social interactions. In freely moving, socially engaging animals, we recorded VMHvl electrophysiology.

We argue that VMHvl cells encode at least three aggression-related characteristics.

  • The overall aggressive state of the animal (motivation).
  • The detection of aggression-provoking sensory cues (sensation).
  • The initiation and execution of attack and aggression-seeking behaviors (actions).

We think that the baseline spiking activity of VMHvl cells encodes the aggressive state, while sudden changes encode sensory information and motor activities.

Aggressive Arousal State

VMHvl activity increases soon once an invader is introduced. This increase in spontaneous activity is unrelated to any behavior and accounts for ~50% of the VMHvl firing rate rise.

VMHvl activity can be increased after the intruder is removed. After intruder elimination, VMHvl activity increases along with aggression. If a second intruder comes in soon after the first, it slows down attacks and makes them less likely to happen.

In self-initiated aggression experiments, after the animal acquired the task contingency, a prolonged increase in spiking activity was found after the nose poking equipment was brought into the intruder's cage but before any nose poking or attack.

Consistent with the animal's heightened hostility during the self-initiated aggression task, the resident male assaults the intruder as soon as he's available. Electrophysiological and behavioral findings lead us to hypothesize that VMHvl activity signals animal aggression.

Aggression-Provoking Olfactory Cues

VMHvl cells respond to aggression-provoking olfactory inputs. During male intruder investigations, male-responsive VMHvl cells increase activity.VMHvl activity rose in a subset of cells when males examined invader urine.

Urine contains pheromones that indicate an animal's sex, physiological, and social state. When given to an invading mouse, the male mouse urine contains volatiles and significant urinary proteins that induce aggression.

Castrated male intruders, whose urine contains fewer volatiles, are less likely to be attacked by resident male mice, and castrated male mouse urine generates less VMHvl cell activity than intact male mouse urine. Male mice rarely attack female mice, and only a small number of male VMHvl neurons are stimulated by female urine.

Aggressive Actions

During social interactions, VMHvl cells are most active during attacks. Activity in responsive cells rises prior to attack (~1 s), peaks at attack commencement, and declines swiftly during behavioral offset.

Importantly, non-attacking motions don't anticipate VMHvl activity. Several lines of evidence suggest this heightened activity during an attack cannot be explained by sensory cues alone. First, assault reaction is higher than investigation response.

Second, in isolated aggression trials (attack not preceded or followed by attack), attack responses are much higher than in investigation trials.

Third, in a linear regression model that looks at the relationship between behavioral parameters and VMHvl cell activity, we found that adding a "latency to attack" parameter can improve model fit in a subpopulation of cells much more than what can be explained by animal distance (an estimate of sensory input) and animal movement velocity.

This evidence supports the concept that VMHvl activity carries attack initiation information independently of environmental signals. Using a self-initiated aggression seeking test to differentiate seeking and attack, we discovered that a subgroup of VMHvl cells increased spiking activity prior to and during nose poking once the animal understood the association. This shows that VMHvl cells signal both physical and learning attacks.

Experience-Dependent Changes In VMHvl Cell Responses

Mounting data reveals that VMHvl cell response qualities are not fixed, as in a "hard-wired" intrinsic circuit, but are constantly modified. Remedios et al. looked at the activity of VMHvl cells over the course of several days as males met male and female invaders and got more social experience.

In naive, unexperienced guys, VMHvl cell responses during male and female examination largely overlap. However, a brief sexual experience with a female generated significant divergence. This difference only happened when animals started to mount each other and fight, which suggests that brain responses and social actions are linked.

In addition, self-initiated aggression seeking training changed VMHvl activity. Before animals learned that poking their nose meant they would attack, few VMHvl cells responded to poking.

VMHvl cells showed clear increases in activity before, during, and after nose poking as animals learned the task. This showed that they could change their responses as they learned more about the task.

An aggressive looking man shouting
An aggressive looking man shouting

Circuits For Olfactory Input

VMHvl responses that signify aggression, sensory detection, and aggressive action may occur from sensory inputs and neuromodulatory tone alterations. Because olfactory pathways have been found, we know the most about how VMHvl responds to smells.

The VMHvl receives volatile and pheromone information from the medial amygdala (MEA) and bed nucleus of stria terminalis (BNST). Volatile information travels through the main olfactory epithelium, main olfactory bulb, and posterolateral cortical amygdala (plCOA) to the MEA and BNST. Pheromone information travels through the vomeronasal organ (VNO) and accessory olfactory bulb (AOB) to the MEA and BNST.

Recent tracing studies reveal MOB mitral and tufted cells project to the MEA. The volatile and pheromone information from the MEA and BNST can reach the VMHvl either directly or indirectly through the ventral part of the premammillary nucleus (PMv).

When the PMv is inactivated, the VMHvl response to an aggression-provoking conspecific is essentially diminished.

Neuromodulatory Inputs And Aggressive State

Increased VMHvl spontaneous spiking during a heightened aggressive state may be partly due to invader sensory inputs, but this is unlikely to account for all activity changes, given these alterations remain after aggressive stimuli are removed. We think a sluggish neuromodulatory or neuroendocrine mechanism may potentially be involved.

In vitro extracellular slice recordings showed VMHvl cells respond to acetylcholine, norepinephrine, serotonin, and dopamine. The Gi-coupled serotonin receptor 1A (5HT1A) and dopamine receptor D2 (D2R) in the area may explain why serotonin and dopamine are mostly inhibitory.

Norepinephrine elicits both excitatory and inhibitory responses in VMHvl cells, possibly due to Gq coupled α1a–adrenergic receptors and to a lesser extent, Gi linked α2c–adrenergic receptors. Acetylcholine excites VMHvl cells through nicotinic and muscarinic receptors.

VMH cells express high-permeability 7 nicotinic receptors, Gq-coupled M1, M3, and M5, and Gi-coupled M2 and M4. Muscarinic stimulation can induce plateau potential and prolonged spiking activity in the cortex and hippocampus, which may be relevant for increasing spontaneous VMHvl cell activity.

Circuit Mechanisms For Increasing VMHvl Activity To Initiate Attack

Optogenetic manipulations show that VMHvl activation increases attack. VMHvl activity increases during and before attacks, according to electrophysiological data.

What circuit mechanisms cause this excitatory response before and during attack? Upstream inputs and local excitatory networks may be responsible. The VMHvl receives input from local cells, neighboring hypothalamic areas, and beyond. The VMHvl receives more inhibitory than excitatory inputs.

The VMH is glutamatergic with few inhibitory neurons. There are a lot of GABAergic cells in the lateral hypothalamus, juxtaventromedial region, ventral zone, and tuberal nucleus (LHAjvv, TU), which may be a direct inhibitory drive.

Tracing studies show numerous projections from the VMH's surrounding regions to the VMH, suggesting robust local regulation of VMHvl activity. In addition to local inhibition, antegrade tracing studies show that the MEA, BNST, lateral septum (LS), and medial preoptic area (MPOA), all of which have GABAergic cells, send a lot of information to the VMHvl.

Optogenetic activation of MEA GABAergic cells elicits instantaneous attack, suggesting that the attack could be launched upstream of the VMHvl, but it is unclear whether this is by its direct projection to the VMHvl or not.

Excitatory inputs to VMHvl are less investigated than inhibitory inputs. They contain the ventral premammalian nucleus (PMv), basomedial amygdala posterior part (BMAp), posterior amygdala (PA), and the ventral subiculum (SUBv). The role of these glutamatergic areas in aggression is uncertain.

How The VMHvl Influences Social Perception And Action Circuits

Aggressive State And The Perception Of An Opponent

A motivated animal perceives sensory stimuli differently. Hunger affects food's attraction, whereas sexual arousal affects a possible mate's. Subthreshold electric stimulation of the hypothalamic attack area causes a change in social behavior from being friendly to being anxious and touchy.

The unknown are the brain mechanisms that affect perception with motivation. Livneh et al. found that hunger affects the insular cortex's reaction to food reward.

In famished mice, insular cortex neurons respond dramatically to food, but not when full. Importantly, stimulating the AGRP neurons brought back the food responses of the insular cortical neurons in animals that were already full.

AGRP neurons transmit to the insular cortex via the paraventricular thalamus (PVT) and basomedial amygdala (BMA). This study uncovered a putative circuit by which subcortical motivation affects cortical perception.

How The VMHvl Affects Midbrain Structures During An Attack

The VMHvl assault signal must activate premotor regions to drive motor execution. Periaqueductal gray (PAG) is the most plausible relay between VMHvl and spinal cord motor neurons. The PAG surrounds the cerebral aqueduct.

PAG neurons project to the nucleus raphe magnus (NRM) and pallidus (NRP), the ventral caudal pontine, and the medullary reticular formation, which project diffusely but robustly to all gray matter along the spinal cord. The VMHvl to PAG projection is well-known.

The Allan brain atlas says that six of the ten strongest terminal fields in the PAG were made by the VMH.

The remaining 4 top spots were taken by areas close to the VMH, such as the tubular and lateral hypothalamic areas, which receive considerable input from the VMHvl. Direct or indirect projections from the VMHvl to the PAG are likely to change how PAG cells work.

People Also Ask

What Is An Example Of An Aggression?

Bullying, slander, and playing friends off one another are a few examples. A hostile act of aggression is an emotional outburst or a retaliatory action that has the intention of harming or destroying another person or object. Any covert show of hostility might be considered passive aggression.

What Is Aggression Behavior?

A child or young person engages in aggressive conduct when they behave hostilely towards their siblings, peers, or adults. Both verbal and physical aggression are examples of it. Your child or young person may be aggressive for a variety of reasons. They might experience fear and unsafety.

What Are The Four Types Of Aggression?

Any action that causes harm to a person, an animal, their feelings, or property is considered to be aggressive. Anger can be expressed physically or verbally.There are four types of aggressive behavior: hostile, accidental, expressive, and instrumental.

What Is Emotional Aggression?

Emotional or impulsive aggression is anger that is mostly caused by sudden feelings and doesn't have much to do with planning or intentions.

Final Words

Aggression research has picked up steam again after several decades of relative sluggishness. Recent studies that used genetically specific, cell-type specific manipulation, tracing, and in vivo recording have helped us learn more about the parts of the brain that are important for aggression.

GABAergic neurons in the lateral habenula, serotonin cells in the dorsal raphe, GABAergic neurons in the lateral septum, and pyramidal cells in the prefrontal cortex, in addition to the VMHvl and associated regions like the MEA and VTA, have also been shown to affect aggression.

Although efforts to comprehend the endogenous responses of the cells during natural behaviors are still restricted, neuronal populations that can modify aggressive behaviors are constantly being uncovered. Still, the VMHvl is the only place where in-depth research has been done on the electrical responses to aggressive behavior.

The interpretation of the behavioral alterations brought on by the manipulation and comprehension of the functions of these cells in the whole-brain aggressiveness circuit depends heavily on this knowledge. We think that by combining research on connections, causes, and correlations with physiology, a complete and well-connected aggressiveness circuit will be found.

About The Authors

Suleman Shah

Suleman Shah - Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences. Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA). Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.

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