In the labyrinth of the human brain, the mechanisms governing fear responses hold profound implications for understanding mental health disorders like post-traumatic stress disorder and anxiety.  

Jonathan Fadok’s research explores how the brain generates defensive behaviors in response to threatening stimuli. Fadok, associate professor in Tulane University’s School of Science and Engineering, and his team aim to uncover the neural basis of fear-related disorders by studying these processes in mice.  

Fadok emphasizes that people with fear-related mental health disorders often experience disproportionate reactions to perceived threats. 

“A large percentage of individuals who experience the same traumas will recover with time, but there’s a certain subset of individuals that develop post-traumatic stress disorder…They can have exaggerated responses to stimuli that are similar to the traumatic experience,” Fadok said. “What we’re hoping to do in the mouse is to understand how the brain generates and coordinates defensive responses to threat.”  

Fadok hopes this research will help his team better understand fear-related disorders. Fadok and his team aim to identify specific types of neurons or neural pathways that generate fear by studying brain activity in mice. Once identified, genetic analysis of these neurons can reveal potential targets in the brain that pharmaceuticals can act on.  

“If you find a pathway in the brain that is involved in a high fear state, you can develop a way of modulating the activity of it, and maybe that is something that could help individuals,” Fadok said.   

Additionally, researchers can apply techniques such as cognitive behavioral therapy to target maladaptive brain activity.  

“In a mouse, you can actually tag the neurons that are involved in a learning event using genetic tools,” Fadok said. “One thing that I think would be cool would be to label the engram for a bad memory and see if you can condition the animal to turn that bad memory into one that’s rewarding.” 

An engram for a memory is a group of neurons that, when activated by similar stimuli, can produce memory retrieval. By targeting engrams, there may be a precedent for converting a bad memory into a positive one.   

Recently, the Fadok lab made a groundbreaking discovery involving a previously unknown projection of the amygdala. Despite the extensive study of the prefrontal cortex and amygdala, scientists had never documented this projection before. The amygdala is known for its implication in emotional processing; however, this novel region may also be linked to “escape behavior” when confronted with a threat. 

“We did these very simple neuroanatomical experiments, and we located this region, and we repeated it, and we saw it again. Then we just started testing and using various tools to try to understand what the role of this projection was,” Fadok said. “We found that it was heavily involved in generating escape behavior.” 

Fadok said that every experiment brings excitement, especially when uncovering something new.  

In the future, Fadok’s research will promote even more advancements in understanding post-traumatic stress disorder. Two newly secured grants will allow the team to investigate PTSD further. Beyond these studies, Fadok envisions developing broader conceptual models to examine how a small number of neurons generate so many different types of outcomes. There is also potential for intersectional research that combines different areas of study.  

“I would like to collaborate, for instance, with philosophers just to try to develop a larger concept,” Fadok said.  

Working with academics from different fields ideally leads to testable hypotheses, paving the way for even more groundbreaking discoveries.