Essentials: The Biology of Aggression, Mating & Arousal | Dr. David Anderson
In a Nutshell
Emotions are persistent, generalizing brain states with arousal and valence dimensions, distinct from reflexes, controlling behaviors like aggression via the ventromedial hypothalamus (VMH), where adjacent neurons drive offensive aggression (rewarding in males, estrogen-dependent) or fear, with evolutionary and functional crosstalk inhibiting aggression during fear or mating (via MPOA). VMH integrates sensory inputs for hydraulic "pressure to attack," modulated by hormones, tachykinins (upregulated by isolation to boost aggression), and PAG for pain suppression during innate behaviors. Bidirectional brain-body loops via vagus nerve and somatic markers underpin subjective feelings, highlighting causal neural targets for future mental health treatments.
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Andrew Huberman introduces Huberman Lab Essentials, revisiting past episodes for science-based tools on mental health, physical health, and performance. He is a professor of neurobiology and ophthalmology at Stanford School of Medicine. Discussion with Dr. David Anderson begins.
Emotions are a type of internal state, like arousal, motivation, or sleep. States change the brain's input-output transformation. When asleep, you don't hear what you would awake. Emotion is a class of state controlling behavior. Viewing emotion as a state focuses on neurobiological rather than psychological processes. Many equate emotion with feeling, a subjective sense studied only in humans by asking them, as people are the only animals we understand speech from.
Emotion is the part of the iceberg below the surface of the water. The feeling part is the tip.
Emotions have two dimensions: arousal and valence. Ralph Adolphs and Anderson expand to components distinguishing emotion states from motivational states. Key properties:
- Persistence: Distinguishes state-driven behaviors from reflexes. Reflexes terminate with stimulus offset (e.g., knee-jerk). Emotions outlast stimuli. Example: Hearing rattlesnake rattle causes jump; heart beats, palms sweat after snake leaves; hypervigilant, stop at snake-like stick.
- Not all states persist (e.g., hunger ends after eating).
- Anger persists post-fight, takes time to calm.
- Generalization: Triggered in one situation, applies to another. Example: Kid screaming—good day at work: soothe; bad day: react differently.
Aggression describes behavior, not internal state. Can reflect anger, fear, or hunger (predatory aggression). Da Lin's work in Anderson's lab used optogenetics to activate ventromedial hypothalamus (VMH) neurons evoking aggression in mice, following Walter Hess's Nobel-winning cat experiments.
Hess described:
- Defensive rage: Ears back, teeth bared, hissing.
- Predatory aggression: Ears forward, paw-batting mouselike object.
VMH like pear on ground: fat bottom has aggression neurons; upper part has fear neurons. Da Lin (now at NYU) and Anna Grace Furlonger show VMH stimulation elicits offensive aggression, rewarding to male mice. Males learn to poke nose/press bar to fight subordinate male; positive valence.
Aggressiveness state is multifaceted, depends on type, involves different circuits.
Evolutionary: Defensive behaviors/fear arose before offensive aggression for predation defense; safety allows alpha competition. Brain regions evolve by duplication/modification of preexisting populations, placing them adjacent.
Functional: Strong fear shuts down offensive aggression; defensive aggression enhanced by fear (rats). Proximity facilitates inhibition. Stimulating top fear neurons during fight stops it; animals freeze. Fear hierarchically dominant over offensive aggression. VMH also mixes metabolic neurons.
Distinguish homeostatic behaviors (need-based: hunger, thirst, temperature) from others. Thermostat model: set point, deviate, correct back (e.g., hot → AC).
Hydraulic pressure from deprivation (need) or desire (drive). Neural activity gradually increases in specific brain region. Example: Hypothalamus feeding area (Scott Sternson et al.): hungrier → higher activity; eating → activity drops.
In aggression: Stronger optogenetic VMH drive → hair-trigger fighting. VMH projects to/receives from ~30 brain regions; antenna (integrates smell, vision, mechanosensation) and broadcaster of low-dimensional 'pressure to attack' representation. Aggression risky (could lose/killed); brain does cost-benefit analysis.
Myth: Testosterone makes aggressive; estrogen placid/emotional—false. VMH aggression neurons marked by estrogen receptor. Knockout in adult male mice → no fighting. Nirao Sha (Stanford, Anderson's former PhD student): Castrate mouse → loses fighting; rescue with testosterone or estrogen implant (bypasses testosterone via aromatization by aromatase enzyme). Aromatase inhibitors used in breast cancer chemotherapy.
Male mice fight readily. Females fight only when nursing pups post-litter; hyperaggressive window ends at weaning. Virgin female with male: sexually receptive, mates. Post-pups, same male: attacks.
Mengyu Liu's work: Female VMH has two estrogen receptor neuron subsets—one for fighting, one for mating.
Sex differences:
- Male VMH: male-specific + generic aggression neurons.
- Female VMH: female-specific mating cells (absent in males).
Mating behaviors vary across species/humans (aggressive or not). In VMHvl aggression neurons (males): subset activated by females during mating. Female-selective neurons likely part of mating; shutting down impairs mating. Stimulation unknown (activates aggression neurons too).
VMH not traditional male sexual behavior area (medial preoptic area, MPOA). MPOA neurons stimulate mating: Activating during male-male attack → stops fighting, sings, mounts target male ('make love, not war'). VMH: 'make war, not love'. Dense interconnections between VMH/MPOA; possible cooperative/antagonistic interactions determine aggression vs. mating (e.g., lions biting during mating).
Wiring allows 'make love' to turn to growl. Raises question: Serial rapists/sexual violence may have crossed wires making blended states rewarding.
PAG implicated in every innate behavior. Like telephone switchboard routing info. Cross-section like toilet water with clock face sectors (1-12+); hypothalamic neurons project to sectors topographically along dorsal-ventral/medial axes determining behavior (evidence points there, not fully mapped).
Martial arts anecdote: Little pain during fight, hurts after → endogenous pain control.
Fear-induced analgesia: High fear suppresses pain (defensive). Adrenal medulla releases bovine adrenal medullary peptide (22 amino acids); analgesic, activates receptor Anderson discovered (thought pro-pain, actually inhibits). Possible in offensive aggression/mating; mechanisms at PAG/spinal cord (PAG continuous with spinal cord).
Tachykinins: Neuropeptide family (short proteins, gene-encoded, released with glutamate). Tachykinin 1 (substance P) promotes inflammatory pain.
Unbiased screen: Drosophila tachykinin neurons promote aggression via peptide release.
Social isolation increases aggression (flies, people, social animals). Flies: Isolation ↑ tachykinin; knockout prevents.
Mice: Moriel Zelikovsky (now U. Utah): 2-week isolation → massive tachykinin 2 upregulation (brain glows green with fluorescent tag). Causes ↑ aggression, fear, anxiety.
Drugs blocking tachykinin receptor (e.g., osanotanant, tested/abandoned in humans): Block all isolation effects. Mice 'chill' (not sedative). Isolated aggressive mouse returned to brothers → no attack, happy.
Potential: Test osanotanant (good safety) in humans under isolation/bereavement stress; hard economically.
Anderson and Ralph Adolphs' book important for public. Heat map of subjective reports: Where people feel emotions (angry, sad, calm, lonely) in body/head.
Not from physiological measurement. Somatic marker hypothesis by Antonio Damasio (neurologist):
This relates to the somatic marker hypothesis proposed by Antonio Damasio, a neurologist at USC. The idea is that our subjective feeling of a particular emotion is in part associated with a sensation of something happening in a particular part of the body, such as the gut or the heart. If there is a physiology underlying these heat maps, it could reflect increased blood flow to these different structures, which in turn reflects bidirectional communication between the brain and the body, mediated by the peripheral nervous system—the sympathetic and parasympathetic nervous systems—which control heart rate, blood pressure, and blood vessel dilation. Those neurons receive input from the hypothalamus and other central brain regions that control their activity.
When the brain is put in a particular state, it activates sympathetic and parasympathetic neurons, which have effects on the heart and blood pressure. These in turn feed back onto the brain through the sensory system. A large part of this bidirectional communication is also mediated through the vagus nerve.
The vagus nerve is a bundle of nerve fibers that comes out of the skull, out of the central nervous system, and sends fibers into the heart, gut, and all sorts of visceral organs. That information is both afferent (sensory input from the body to the brain) and efferent (output from the brain to the body). The vagal fibers sense things happening in the body—for example, the reason you feel your stomach tied up in knots when tense is that those vagal fibers are sensing the contraction of the gut muscles. They are also efferent, meaning information from the brain can influence those peripheral organs.
Recent work from a number of labs in the last 6 months has started decoding the components of the different fibers in the vagus nerve, revealing amazing specificity. There are specific vagal nerves that go to the lung to control breathing responses, to the gut, and to other organs—almost like a set of color-coded, labeled lines for those functions. How those vagal afferents play a role in the playing out of emotional states is a fascinating question that researchers are just beginning to explore.
Exciting developments include tools that will allow turning on or off specific subsets of fibers within the vagus nerve to ask how that affects particular emotional behaviors. This brain-body connection is critical not just for the gut but for the heart, lungs, and all kinds of other parts of the body. Darwin recognized this as well, and it is a central feature of emotional states that underlies our subjective feelings of emotion.
I really have appreciated your questions. They've all been right on the money. You've hit all of the critical important issues in this field and you've uncovered what is known, the little bit that is known, and how much is not known.
It is important to emphasize the unknown things because that is what the next generation of neuroscientists has to solve. This will help attract young people into the field, which is so important particularly for understanding mental illness, mental health, and psychiatry. We have got to figure out how emotion systems are controlled in a causal way if we ever want to improve on the psychiatric treatments we have now, and that is going to require the next generation coming into the field.
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