Pain, Fear, and Pleasure Share the Same Brain Circuit

A powerful brain circuit that responds to rewarding events has just been discovered in a brain region previously associated with controlling reactions to fear and pain.

The findings, published in the journal Neuron, could help to explain why many of us experience fear and pleasure simultaneously, such as when watching a scary movie or riding a roller coaster. You may even crave such moments, as the brain region - called the central amygdala - appears to drive what are known as appetitive behaviors.

"Appetitive behaviors increase pleasure and satisfy an animal's certain needs, such as consumption of food or water when you are hungry or thirsty," Xiangyu Zhang, one of the paper's lead authors, told Seeker. "The central amygdala receives sensory information related to such behaviors."

"Amygdala" is the ancient Greek word for almond. In terms of brain anatomy, the word refers to an almond-shaped mass of gray matter located inside each cerebral hemisphere.

Last year, the lab of senior author Susumu Tonegawa, director of the RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, identified two distinct populations of neurons in another part of this brain structure, called the basolateral amygdala (BLA). This region of the brain is hardly blah, though, as Tonegawa and his team determined that the two groups of neurons are genetically programmed to encode either fearful or happy memories.

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For the new study, Zhang, co-lead author Joshua Kim, and their colleagues in Tonegawa's lab again investigated the BLA neurons as well as others within the amygdala.

Using a technique called optogenetics, they injected a virus that expresses light-sensitive proteins into the central amygdala of mice.

"The mice sought more light after being exposed, suggesting that activation of the central amygdala elicits rewarding behaviors," Zhang said.

The researchers next examined the neural activity of this part of the brain in response to other stimuli, including things that would normally be threatening to the tiny rodents, such as slight foot shocks or exposure to quinine water with a bitter taste. In those cases, the circuitry linked to pleasure in the central amygdala was not activated.

The researchers determined that more than 90 percent of the central amygdala is packed with cells that respond to rewarding events. A circuit that controls responses to fearful events is also present, but to a much lesser degree.

"It's surprising that positive-behavior-promoting (neuronal) subsets are so abundant, which is contrary to what many people in the field have been thinking," Tonegawa said in a statement.

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He explained that the traditional view of the amygdala is that it is involved primarily in fear-related behaviors. He and his team now think otherwise.

In fact, humans might have more potential for happiness than most of us might tend to imagine. The researchers are even studying the role of BLA neurons in fear extinction, which is the process of rewriting fearful memories so that they are associated with more positive ones. The approach is already being used to treat disorders, such as depression and post-traumatic stress disorder.

The researchers can rewrite bad memories with precision in mice, such as by switching a memory about the aforementioned yucky-tasting (to rodents) quinine water with a good memory of interacting with a desired member of the opposite sex.

"Emotions are mediated by complicated neural pathways," Zhang said. "Our latest findings concerning the central amygdala, a well-known player in the neural circuits of emotion, bring us one step closer to solving the complicated puzzle."