The Biology of Aggression, Mating, & Arousal | Dr. David Anderson

Andrew Huberman introduces David Anderson, a professor of biology at Caltech, a member of the National Academy of Sciences, and a Howard Hughes Medical Institute investigator since 1989. Anderson studies emotions and states of mind and body. The episode covers aggression, rage, sexual behavior and where they overlap, and touches on peptides that may govern anxiety and aggression. Huberman also recommends Anderson's popular book, "The Nature of the Beast: How Emotions Guide Us," saying much of it contrasts with common myths about emotions and biology.

Huberman opens by asking whether emotions and states differ. Anderson answers that he sees emotions as one type of internal state, alongside arousal, motivation and sleep. His working definition is functional: internal states change how the brain transforms input into output. A sleeping person does not hear a sound they would hear awake, unless it is very loud. Framing emotion as a state makes it a neurobiological process instead of a psychological one, and that sidesteps the definitional problem of equating emotion with feeling. Feelings are subjective, and studying them requires asking someone, which limits that work to humans.

If you think of an iceberg, it's the part of the iceberg that's below the surface of the water. The feeling part is the tip that's sort of floating above the surface of your consciousness.

Anderson does not dismiss feelings. He says they matter, but understanding them requires understanding consciousness, and "we're not ready to study that in animals yet."

Asked what lies below the tip of the iceberg, Anderson describes states as having facets or dimensions. Some researchers use only two: arousal (intensity) and valence (positive or negative). Anderson and Ralph Adolphs have tried to add more components, especially ones that separate emotion states from motivational states, which are closely related.

Persistence: reflexes start and stop with the stimulus, like a knee tapped with a hammer, while emotions often outlast what triggered them. After hearing a rattlesnake on a trail, the racing heart, sweaty palms, dry mouth and hypervigilance continue after the snake has gone, so even a stick can make you jump. Not every state persists in this way: hunger ends once you have eaten, but anger after a fight can last a long time. Generalization: a state triggered in one setting carries over to another. Anderson's example is a parent coming home to a screaming child, who may soothe it after a good day at work or scream at it after a bad one, carrying over a state that began with something the boss said. Motivation states, by contrast, are specific (find and eat food, obtain and consume water) and serve homeostatic maintenance.

For Anderson, splitting states into components turns them into concrete research questions: what makes a state persist, what gives it positive or negative valence, and how its intensity is turned up or down. He says these questions can now be asked in the brain with current tools.

Huberman notes that a person can be highly alert while stressed and worried, or highly alert while happy, or sexually aroused. He asks whether a simple neurochemical signature flips valence, for example whether arousal with extra dopamine release is positive and arousal with low dopamine is negative.

Anderson declines that framing. He thinks a valence flip is more likely a circuit flip, where different circuits are engaged, and the same chemical, even dopamine, may take part in both positively and negatively valenced arousal. He says this is why arousal and valence are treated as separate axes. He then reframes the question: is arousal generic across the brain, or are there behavior-specific kinds of arousal?

As evidence, he cites a 2009 fruit fly paper from his lab that found signs of two arousal states. One is sleep-wake arousal. The other is a startle-like response to a noxious mechanical stimulus: flies puffed with air return more and more vigorously, "kind of like trying to swat the wasp away from your burger at a picnic table." Both forms required dopamine, but they acted through completely separable neural circuits. Anderson draws two conclusions: the circuit determines the type of arousal, and arousal is not unitary.

I think the jury is still out as to whether there is such a thing as completely generalized arousal or not.

He grants that some researchers would argue generalized arousal exists, but he says domain-specific or behavior-specific arousal deserves more attention. Huberman says he had pictured arousal as one continuum running from panic attack to coma, with alert calm in the middle. Valence, he says, suggests there may be multiple circuits and mechanisms for arousal, involving both neurochemicals and different neural pathways.

Huberman asks about aggression and how it varies, mentioning the recent school shooting in Texas as an act that clearly included aggression but may differ from all-out rage or controlled aggression. Anderson first makes a distinction: to him, "aggression" describes behavior more than an internal state. It may reflect what humans would call anger, or it may reflect fear, or hunger in the case of predatory aggression.

He traces the history. Walter Hess's Nobel Prize-winning work in cats, and later work by Menno Kroon in rats, used electrical stimulation of the hypothalamus. It could make a placid cat bare its teeth, hiss and nearly strike the experimenter, and it could make rats fight. Hess already saw two types of aggression depending on where the electrode sat: "defensive rage," with ears back, teeth bared and hissing, and predatory aggression, with ears forward and the cat batting at a mouse-like object as if to catch and eat it. Different forms of aggression were already known to be segregated in the brain.

Around 2008 to 2009, after starting aggression work in fruit flies, Anderson wanted to move it into mice so genetic tools could be used. Dayu Lin, an electrophysiologist in his lab, first repeated electrical stimulation of the ventromedial hypothalamus (VMH), as had been done in rats, cats, hamsters and monkeys. Over 40 different trials it did not produce aggression. It produced fear behaviors instead: freezing, cornering and crouching. Kroon was also mystified. Anderson concluded that this was why no paper on brain-stimulated aggression in mice had appeared in 50 years: "the experiment doesn't work."

Anderson says his one contribution was persuading Lin to try optogenetics, which had recently begun to be used deep in the brain through work by Karl Deisseroth and others, because it could be aimed more specifically than electrical current. Lin was skeptical.

"Never going to work. If it doesn't work with electricity, why should it work with optogenetics?"

It did work: optogenetic stimulation of VMH triggered aggression. Anderson's after-the-fact explanation uses the image of a pear sitting on the ground. Aggression neurons sit in the wide lower part and fear neurons in the upper part. In a mouse the structure is so small that injected current may spread through the whole pear and activate fear circuits, which "totally dominate aggression." Optogenetics limits stimulation to the neurons carrying the channelrhodopsin gene. He presents this as a retrospective interpretation ("I think the reason") and not a tested result.