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The Quad: Research at UCLA labs yields insights about brain mechanisms controlling fear

(Isabella Lee/Daily Bruin)

By Alex Foyt

June 20, 2022 1:06 p.m.

This post was updated July 10 at 10:43 p.m.

UCLA researchers are unraveling the biological mechanisms behind the sensation of fear, a powerful physiological response to perceived dangers that can bypass conscious thought and alter behavior.

The fear response is initiated by a structure in the brain known as the amygdala, which filters through sensory information for a stimulus indicating an individual is in danger.

Michael S. Fanselow, a professor of psychology and principal investigator at Fanselow Research Lab, said that once such a stimulus is detected, the amygdala sends a signal to an area called the central nucleus, which activates the different components of the body that elicit the fear response.

“There are signals out from the central nucleus that go into the places like the brainstem – regions that control our heart rate,” Fanselow said. “It extends to other regions like the hypothalamus, which control our blood pressure and our stress hormone responses.”

These pathways lead to the fight-or-flight physiological responses associated with fear, such as a racing heart and clouded logical thought, according to UW Medicine.

Fanselow said the central nucleus can also send signals to the midbrain, which drives behavioral responses such as freezing. This behavior, which evolved as a way to hide from predators, can override conscious control in humans and rodents alike.

UCLA alumnus Fiona Huang said her recent work in the Fanselow Research Lab has focused on understanding the role that two different proteins, the GluA1 AMPA receptor and mTOR, play in learning new fears.

Having more GluA1 AMPA receptors on the receiving end of a neuron changes the chemical interactions that occur during excitation in a way that facilitates long-term memory formation, Huang said in an emailed statement.

Huang added that after experiments in which the lab members taught the rats new fears, preliminary data showed an increase in the number of GluA1 AMPA receptors in the amygdala, a brain structure also involved in the encoding and extinction of fear memories.

Huang said the mTOR protein may directly influence this process by signaling neural cells to increase their numbers of GluA1 AMPA receptors and also by moderating energy levels in those cells during memory formation and consolidation.

Avishek Adhikari is an assistant professor of psychology and a principal investigator at the Avi Adhikari Lab at UCLA. Adhikari said he studies brain circuits that control fear in mice by identifying different neurons in the brain that manage different behaviors in response to threats.

Adhikari said his lab has mapped out the neural circuits that control escape from dangerous situations that require navigational skills, such as fleeing from a burning house.

“We found out a brain region in the hypothalamus that, when activated, it coordinates the actions of both these circuits that increase the urge to escape with other circuits that control this navigation ability to know which route to take,” Adhikari said.

Adhikari said the terms anxiety, fear and panic describe distinct circuits of the brain that coordinate different behaviors in response to how likely a threat is to occur at any given moment. Adhikari added that these distinctions have important implications when treating disorders in those circuits.

“This anxiety state leads to something like generalized anxiety disorder where … one of the symptoms is constant rumination, worrying about potential problems,” Adhikari said. “Panic attacks … are a very different sort of phenomena where they last … a few minutes, but it’s very overwhelming and intense.”

While current research is illuminating the secrets of fear as technological developments pave the way for new treatments, Fanselow said treatments are already available for people that suffer from many fear disorders, including post-traumatic stress disorder and phobias.

“One of the things is for people to recognize that we do have solutions to this. We’re getting better, but we do have solutions to a lot of these things,” Fanselow said.

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