As Halloween approaches, fear takes center stage in haunted houses, scary movies, and spooky stories. But fear isn’t just a seasonal thrill—it’s a deeply ingrained response that scientists have been studying for decades. Mice and rats have become key subjects in fear research, helping us understand the science of fear and how it shapes behavior.
Hope for PTSD Treatment
Survival would be impossible without fear, an evolutionary response triggered by imminent danger. But what’s going on in cases like post-traumatic stress disorder (PTSD), when the body triggers a fear response in the absence of danger?
A new study by scientists at the University of California, San Diego shed new light on the mechanism in the brain that causes fear to return.
To find the chemical basis of general fear that occurs when there is no immediate danger, the team studied the periaqueductal gray and dorsal raphe nucleus area of the brain in mice.
Using shocks to their paws induce different levels of fear, they observed the activity in these two areas and found that after a stressful event, certain nerve cells in the brain change the chemicals they use to send messages. Specifically, the neurons switched from releasing one chemical, glutamate, to another called GABA. This switch changes the effect of the signals, inhibiting rather than exciting the nerve cells. As a result, the mice showed fear in environments other than the one where they first experienced acute stress.
To extrapolate the findings to humans, the researchers analyzed brain samples from 12 deceased individuals, half with PTSD and half without, and found that the brain stem tissues of those with PTSD had 26.12% fewer neurons that produced both serotonin and glutamate, while neurons producing both serotonin and GABA increased by 6.5%.
The researchers then returned to the mice to explore ways of blocking generalized fear. Before subjecting the mice to stress by giving them paw shocks, they used a virus to block the gene that produces the GABA neurotransmitter. This successfully prevented the mice from developing generalized fear.
They also discovered that giving the mice an antidepressant called fluoxetine (the active ingredient in Prozac) right after the shocks prevented the change in brain signaling—the mice didn’t experience the switch from glutamate to GABA and didn’t freeze in fear during tests. This suggests that administering fluoxetine immediately after a traumatic event might help prevent people from developing generalized fear.
A Novel Pathway Between Freeze and Flight
When triggered by danger, how does the brain transition from a freeze response to a flight response? Researchers at Tulane University have discovered a previously unknown pathway in the brain that might offer an explanation.
The central amygdala (CeA) is a key part of the brain controlling reactions like freezing and fleeing in response to danger. However, it’s unclear what triggers these strong defensive reactions. Tulane researchers discovered a previously unknown connection from the dorsal peduncular (DP) prefrontal cortex to the CeA, which plays a key role in these responses.
These DP-to-CeA neurons help activate defensive behaviors, such as fleeing or freezing, based on the threat’s intensity. The study showed that this pathway is essential for these reactions, highlighting a new top-down mechanism controlling fear responses.
The identification of the DP-to-CeA pathway could lead to new treatments for maladaptive fear responses like PTSD or other anxiety disorders.
How Do Fearful Memories Form?
A team of researchers in Taiwan has uncovered new information about how fear memories form in the brains of mice, which could lead to new treatments for PTSD. The researchers focused on the central amygdala, an area known to regulate fear emotions, and discovered that a specific group of inhibitory nerve cells in this region plays a key role in managing fear responses.
Traditionally, studies have emphasized the role of excitatory nerve cells in memory storage, neglecting the function of inhibitory cells. This study found that activating these inhibitory cells helps prevent overly intense reactions to fear memories. When researchers inhibited these specific cells in genetically modified mice, the mice showed increased fear responses, such as freezing longer when expecting a shock.
The findings suggest that these inhibitory cells act like a brake on fear reactions, serving as a balancing mechanism to manage fear memories. While the results provide valuable insights into the neural mechanisms of fear memory, it remains to be seen whether the human brain experiences the same effect.
How Do We Know Who to Be Afraid Of?
Scientists at Columbia University have discovered how the brain helps distinguish between safe and threatening individuals, which could offer new insights into fear-related disorders like PTSD and social anxiety.
In investigating the hippocampus, which plays a key role in memory in both humans and mice, they focused on two regions with different functions: CA2, which is involved in social memory, and CA1, which primarily remembers places.
The researchers discovered that CA1 and CA2 perform very specific roles in memory: CA2 helps remember the risk factor associated with specific individuals, while CA1 stores the memory of places where threats occurred.
In an experiment with mice, turning off CA2 made the mice fearful of all strangers, while silencing CA1 made them forget the locations where they were previously shocked. This research suggests that targeting CA2 could help better understand and treat conditions like social anxiety and PTSD, where people struggle to identify who is a threat.
