Supporting Publication: Induction of Fear Extinction with Hippocampal-Infralimbic BDNF
We all have memories of embarrassing or even frightening events that never seem to fade away. I don’t remember what I ate for breakfast last Saturday but I can remember where I was and even what exactly I was wearing when I witnessed the September 11, 2001 events on T.V. Why is it that emotionally charged events create such strong memories that seem to last for an eternity? (That is a plug for a later blog post, how and why fear occurs!) The subtlest reminder such as a sound or a picture can reawaken the awful feelings associated with a memory. In the most extreme cases, such as war veterans with post-traumatic stress disorder (PTSD), these memories can be debilitating and can control one’s life.
What if you could take a pill and have the unwanted memories wiped from your brain? Sounds a little sci-fi, I know, but it may very well be possible in the near future. Researchers at the University of Puerto Rico interested in the neurobiology of learning and memory chose to manipulate one key chemical in the brain in a series of experiments, brain-derived neurotrophic factor (BDNF), that seems to play a significant role in fear-related memories.
These researchers claim that BDNF acts in the brain in a manner that is similar to extinction learning. We all remember Pavlov’s dogs, right? Well in the most typical scenario nowadays, researchers can instill a learned fear into rats (much less expensive than dogs and much less saliva) by applying a small, yet frightening shock while sounding a noise (like playing The Beatles, for instance). The rats become conditioned to The Beatles in a bad way because they fear the pain they will feel from the shock. In most cases the rats will physically express this fear by freezing up in their cage in anticipation of the shock. So are the rats doomed to forever freeze up and experience a panic attack when they hear The Beatles for the rest of their lives?
What a horrible existence… sounds like some frightening Guantanamo experiment. Of course not! Researchers have proven that this fear-conditioned memory can be undone through the process of extinction learning. This is accomplished by doing the exact opposite as before, start playing The Beatles but instead of shocking the rat, give him a piece of cheese (or something else to quell those munchies… we all know the kind of folks that listen to The Beatles).
Ok so we all know what extinction learning is and how it can be accomplished with something like a behavior therapy. The PTSD that is seen in war veterans involves memories that are deeply engrained in the brain and oftentimes behavioral therapy isn’t enough to overcome the neurobiological factors that have taken control.
The researchers at the University of Puerto Rico knew that BDNF played a strong role in fear-related memories and they wanted to know if it could be used to extinguish the learned fear chemically, without any behavior learning. Knowing that the CA1 area of the hippocampus is responsible for producing BDNF, the researchers increased the available supply of hippocampal BDNF in one group of rats and compared this group with a control group.
The control group of rats froze when the fear-conditioned tone was played but the rats with increased BDNF levels surprisingly did not! This group responded instead almost identically to the group of rats that had undergone behavioral extinction learning. Both groups of rats did not freeze up in most cases but instead held their cigarette lighters in the air and swayed back and forth while “Lucy in the Sky with Diamonds” blared from the speakers (in truth, they did nothing because they no longer feared the tone that they had once associated with a painful shock). This result proved that by solely increasing levels of BDNF in the hippocampus, the rats were able to lose their association between a learned memory and fear. The researchers believed that the rats still held the memory of the tone associated with a shock, but the actual fear was greatly reduced.
The possibility of erasing those unwanted memories doesn’t sound so far fetched now, does it? There is certainly a lot of research to be done before we could even begin to consider applying this to the human brain but the prospect is extremely exciting. Anxiety and PTSD can be extremely debilitating because emotionally charged memories can keep the brain from extinguishing strong feelings of fear and thus make us act or think in ways that are not logical. A therapy that focused on BDNF levels in the brain would not necessarily make us forget our bad memories, but it would allow us to better cope with them by allowing the brain manage the associated fear.
A recent study in the journal Military Medicine examined rates of PTSD among 120 soldiers returning from Irag and Afghanistan. They surveyed the service members on their PTSD symptoms, depression, alcohol use, and the frequency at which they had sought out mental health services. This survey showed that 6% had PTSD, 27% abused alcohol, another 6% had problems with both PTSD and alcohol use and 62% were receiving mental health care (therapy and medication). BDNF therapy in the future could very well be a method to help treat these war veterans and allow them to adjust back to a healthy mental civilian lifestyle.