Scientists have discovered how stress turns into fear

 Neuroscientists have discovered how stress turns into fear in the brain—in conditions like PTSD—and a method to block it. Our nervous system is naturally wired to feel fear. Whether triggered by eerie sounds we hear in the dark or the growl of a threatening animal, our fear response is a survival mechanism that tells us to be alert and avoid dangerous situations.

But if fear occurs in the absence of tangible threats, it can harm our well-being. Those who have experienced episodes of severe or life-threatening stress may later experience intense feelings of fear, even in situations where there is no real threat. Experiencing such generalized fear is psychologically damaging and can lead to long-term debilitating mental disorders such as post-traumatic stress disorder (PTSD).

The stress-induced mechanisms that cause our brains to generate feelings of fear in the absence of threats remain largely a mystery. Now, neuroscientists at the University of California, San Diego have identified the changes in brain biochemistry and mapped the neural circuits that cause this generalized feeling of fear. Their research, published in the journal Science, provides new insight into how the fear response can be prevented.

Breakthrough in fear research

In their talk, former UC San Diego Project Scientist Hui-quan Li (now Senior Scientist at Neurocrine Biosciences), Atkinson Family Professor Emeritus Nick Spitzer of the School of Biological Sciences, and their colleagues describe the research behind their discovery of neurotransmitters . — chemical messengers that allow neurons in the brain to communicate with each other — are at the heart of generalized fear caused by stress.

By studying the brains of mice in an area known as the dorsal cingulate (located in the brainstem), the researchers found that acute stress causes chemical signaling in neurons to switch from excitatory "glutamate" neurotransmitters to inhibitory "GABA". , which led to generalized fear reactions.

Insights and Interventions for Generalized Fear

"Our results provide important insights into the mechanisms involved in fear generalization," said Spitzer, of UC San Diego's Department of Neurobiology and the Kavli Institute for the Brain and Mind. "The advantage of understanding these processes at this level of molecular detail—what's happening and where it's happening—allows for interventions that are specific to the mechanism driving the associated disorders."

Building on this new discovery of stress-induced neurotransmitter switching, which is thought to be a form of brain plasticity, researchers examined the post-mortem brains of people who had suffered from PTSD. A similar switching of the neurotransmitter from glutamate to GABA was also confirmed in their brains.

Then the researchers found a way to stop the production of generalized fear. Before experiencing acute stress, they injected mice with adeno-associated virus (AAV) into the dorsal ligament to suppress the gene responsible for GABA synthesis. This method prevented the mice from acquiring generalized fear. In addition, when mice were treated with the antidepressant fluoxetine (branded as Prozac) immediately after a stressful event, the switch in the transmitter and subsequent generalized fear was prevented.

The researchers not only pinpointed the location of the neurons that switched their transmitters, but also demonstrated the connections of these neurons to the central amygdala and lateral hypothalamus, brain regions previously associated with the generation of other fear responses.

"Now that we know the mechanism by which stress-induced fear occurs and the circuitry that implements that fear, interventions can be targeted and specific," Spitzer said.