Joseph LeDoux and the Neuroscience of Fear

"Brain imaging is not a very good way to test subtle distinctions [in the brain]...it's like trying to find out something about New York City by studying New York State," says NYU neuroscientist  Joseph LeDoux, one of the pioneers of neuroscientific animal research back in the 1970s. "Animal research is so important because we can go in and study individual cells and individual synapses on those cells," he says. But can we take the information we learn about the brains of rats and apply that knowledge to the endlessly complex human brain? 


In his second Big Think interview, LeDoux told us that, yes, we can learn much from studying rats' brains, even about things like emotion, which we often attribute solely to humans. "Through the history of psychology, there's been a struggle between what can we learn about psychological states in humans and animals, what can we learn about psychological states by studying conscious states in people and unconscious states," LeDoux explains. In the 1930s and '40s, the behaviorists threw out the idea of consciousness because it is a subjective pehnomenon that cannot be measured. Then the cognitive revolution of the '50s and '60s brought the mind back to psychology, "but it didn't bring back the mind that the behaviorists got rid of," says LeDoux. "When I got interested in emotion in the '70s, emotion was still being thought of in terms of subjective conscious experiences, whereas other aspects of psychology, like perception and memory were thought of as information processing functions." LeDoux revolutionized the study of emotion, especially of fear, by thinking about it in terms of observable behavior. "All animals have to be able to detect danger and respond to danger in order to stay alive, including humans." And because this is such a basic evolutionary adaptation, it functions quite similarly between animals and humans.

The hub of all emotional processing in both human and animal brains is the amygdala, says LeDoux, also the frontman of a rock group called The Amygdaloids. He has spent his career studying this almond-shaped structure, and he gave us a five minute primer on everything we should know about it. "What the amygdala is doing is forming associations between random or neutral external stimuli and the kinds of reinforcing events that will stamp in those experiences in a stronger way," he says. "So its creating what's called Pavlovian associations: you know, stimulus one plus stimulus two; if one of those is a biologically significant stimulus, then the other one will acquire some kind of biological significance itself, whether it’s positive or negative."

LeDoux also talked to us about some of the groundbreaking research to have come out of his his lab in recent years. One discovery dealt with a process called "reconsolidation" of memory. "When you retrieve a memory it becomes unstable and new information can be incorporated into the memory at that point," he says. "It also means that when the memory is unstable, its restabilization process can be blocked. And if you block that, the memory is weakened or dampened. So that's how we've been using reconsolidation to help people with traumatic memories to try and dampen their memories of those traumatic situations."

LeDoux also told us about his current studies of rats with extreme fear. "We can compare animals that are really afraid and those that are not afraid and look in their brains and see if there area any, for example, structural differences in the amygdala."

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Are modern societies trying too hard to be clean, at the detriment to public health? Scientists discovered that a microorganism living in dirt can actually be good for us, potentially helping the body to fight off stress. Harnessing its powers can lead to a "stress vaccine".

Researchers at the University of Colorado Boulder found that the fatty 10(Z)-hexadecenoic acid from the soil-residing bacterium Mycobacterium vaccae aids immune cells in blocking pathways that increase inflammation and the ability to combat stress.

The study's senior author and Integrative Physiology Professor Christopher Lowry described this fat as "one of the main ingredients" in the "special sauce" that causes the beneficial effects of the bacterium.

The finding goes hand in hand with the "hygiene hypothesis," initially proposed in 1989 by the British scientist David Strachan. He maintained that our generally sterile modern world prevents children from being exposed to certain microorganisms, resulting in compromised immune systems and greater incidences of asthma and allergies.

Contemporary research fine-tuned the hypothesis, finding that not interacting with so-called "old friends" or helpful microbes in the soil and the environment, rather than the ones that cause illnesses, is what's detrimental. In particular, our mental health could be at stake.

"The idea is that as humans have moved away from farms and an agricultural or hunter-gatherer existence into cities, we have lost contact with organisms that served to regulate our immune system and suppress inappropriate inflammation," explained Lowry. "That has put us at higher risk for inflammatory disease and stress-related psychiatric disorders."

University of Colorado Boulder

Christopher Lowry

This is not the first study on the subject from Lowry, who published previous work showing the connection between being exposed to healthy bacteria and mental health. He found that being raised with animals and dust in a rural environment helps children develop more stress-proof immune systems. Such kids were also likely to be less at risk for mental illnesses than people living in the city without pets.

Lowry's other work also pointed out that the soil-based bacterium Mycobacterium vaccae acts like an antidepressant when injected into rodents. It alters their behavior and has lasting anti-inflammatory effects on the brain, according to the press release from the University of Colorado Boulder. Prolonged inflammation can lead to such stress-related disorders as PTSD.

The new study from Lowry and his team identified why that worked by pinpointing the specific fatty acid responsible. They showed that when the 10(Z)-hexadecenoic acid gets into cells, it works like a lock, attaching itself to the peroxisome proliferator-activated receptor (PPAR). This allows it to block a number of key pathways responsible for inflammation. Pre-treating the cells with the acid (or lipid) made them withstand inflammation better.

Lowry thinks this understanding can lead to creating a "stress vaccine" that can be given to people in high-stress jobs, like first responders or soldiers. The vaccine can prevent the psychological effects of stress.

What's more, this friendly bacterium is not the only potentially helpful organism we can find in soil.

"This is just one strain of one species of one type of bacterium that is found in the soil but there are millions of other strains in soils," said Lowry. "We are just beginning to see the tip of the iceberg in terms of identifying the mechanisms through which they have evolved to keep us healthy. It should inspire awe in all of us."

Check out the study published in the journal Psychopharmacology.