Innovative research demonstrates how weakening specific fear-related connections in the brain of a mouse can erase previous fear responses to a stimulus. The work may help to build future treatment programs for post-traumatic stress disorder and phobias.
As we evolved, swiftly learning to be afraid of dangerous situations or objects was a vital skill. If we are injured by something, our brain forms a memory linking the stimulus to the production of fear, ensuring that we will always avoid it in the future.
This mechanism works well throughout the animal kingdom; creatures quickly learn what stimuli are dangerous and will, going forward, give them a wide berth.
Sometimes, however, a learned fear response is not healthy. For instance, following a car crash, some people have to relive the experience each time they get into a car. Similarly, individuals with post-traumatic stress disorder (PTSD) may have disproportionately strong fear responses to certain sights, smells, or sounds.
Although medications are available that reduce fear and anxiety across the board, as it stands, it is not possible to target specific stimuli and remove particular fears.
Understanding the fear response
Recently, a group of researchers from the University of California, Riverside designed a way to unhitch benign stimuli from their learned fear response. The team was led by Dr. Jun-Hyeong Cho, an assistant professor of molecular, cell, and systems biology, and Woong Bin Kim, his postdoctoral researcher.
In a nutshell, the team wanted to see if they could weaken the connections between the neurons responsible for an inappropriate fear response. The investigation, using a mouse model, was published in the journal Neuron this week.
Mice were presented with either a high-pitch or low-pitch tone. At the beginning of the study, the mice showed fear to neither sound. Then, each time the high-pitched sound was played, the mice received a mild electric shock to the feet.
Once this pairing had been learned, the high-pitch sound elicited a fear response called freezing behavior in the mice, even when no shock was given, while the low-pitch sound continued to produce no fear response. When the brains of the mice were examined, the team found that synaptic connections that relayed the high-pitch sound to the amygdala were strengthened.
Dr. Cho explains, "In the brain, neurons communicate with each other through synaptic connections, in which signals from one neuron are transmitted to another neuron by means of neurotransmitters."
"We demonstrated that the formation of fear memory associated with a specific auditory cue involves selective strengthening in synaptic connections which convey the auditory signals to the amygdala, a brain area essential for fear learning and memory."
Using light to remove fear
In the next phase of the study, the team wanted to understand whether they could remove or at least reduce this newly learned fear response. They weakened the synaptic connection using a method called optogenetics, which is a procedure wherein genetically modified neurons can be switched on or off by pulses of light.
The researchers found that the neurons responsible for receiving high- and low-pitch sounds were "intermingled," but they were able to single out just those responsible for responding to the high-pitch sound.
"We were able [...] to experimentally stimulate just those neurons that responded to the high-pitch sound. Using low-frequency stimulations with light, we were able to erase the fear memory by artificially weakening the connections conveying the signals of the sensory cue - a high-pitch tone in our experiments - that are associated with the aversive event, namely, the foot shock."
Dr. Jun-Hyeong Cho
The future of fear
The findings further our understanding of how adaptive fear memories for a particular stimulus are encoded. Although earlier research has demonstrated that connections between auditory centers and the amygdala are strengthened when an animal forms a fear memory for an auditory cue, this study had some unexpected results.
Medical News Today recently spoke with Dr. Cho, and he explained, "We were surprised when we found that only a small population of neurons (nerve cells) in these areas were involved in the formation of fear memory for a specific auditory cue."
Of course, the findings are fascinating, but the results are unlikely to be usable in humans for some time. When MNT asked Dr. Cho how long it might take, he said, "Based on recent advances in technology to control neural activity in humans (such as deep brain stimulation and transcranial magnetic stimulation), we expect that we will be able to weaken pathological and maladaptive fear memories in PTSD within the next 10 years."
As with any complex area of research, there are plenty of questions that need answers. Dr. Cho told MNT about his future plans, saying that, "as we discovered the neural mechanism of the formation of fear memory associated with a sensory (auditory) cue, we plan next to investigate how fear memory associated with a context is encoded in the brain."
They will also investigate "how a memory associated with a reward cue is encoded in the brain, which has implications in treating addictive behaviors." PTSD and phobias are notoriously difficult to treat, and this line of research gives some much-needed hope.