Our brains have a built-in mechanism for hiding traumatic and emotionally distressing memories in the recesses of our minds, and now a new study from Northwestern University Feinberg School of Medicine researchers has shed new light on how this process works.
The paper, published earlier this week in the journal Nature Neuroscience, pulls back the curtain on a process known as state-dependent learning, which is believed to help us form memories that are inaccessible to normal consciousness, protecting us from events such as childhood abuse.
While this method protects us from the pain of recalling specific events, they can also lead to an array of different issues, including anxiety, depression, or PTSD. Though they are inaccessible in most situations, memories formed in a particular mood or state can be retrieved when the brain is returned to that state, as demonstrated by the researchers through mouse experiments.
In those experiments, Dr. Jelena Radulovic, professor of bipolar disease at the Feinberg School, and colleagues discovered the mechanism through which state-dependent learning renders these fear-related memories inaccessible to a person’s consciousness for the first time.
Amino acids responsible for this phenomenon
In a statement, Dr. Radulovic said that the findings “show there are multiple pathways to storage of fear-inducing memories, and we identified an important one for fear-related memories.” Their work “could eventually lead to new treatments for patients with psychiatric disorders for whom conscious access to their traumatic memories is needed if they are to recover.”
As the authors explained, it is hard for therapists to help these patients because those individuals themselves are unable to recall the traumatic events at the core of their symptoms. The best way to access these hidden memories is to return the brain to the same state of consciousness as when the memory was encoded, and the new research reveals exactly why this is the case.
A pair of amino acids, glutamate and GABA, are at the center of this phenomenon. The Feinberg School researchers explained that these substances are essentially the brain’s yin and yang. They direct the brain’s emotional tides and control if nerve cells are excited or inhibited. The system is balanced under normal conditions, but when a person becomes hyper-aroused and vigilant, there is a surge in glutamate, the chemical primarily responsible for storing memories.
When glutamate stores memories, they do so in a way that is easy to remember, while GABA blocks the action of this substance, calming us and helping us sleep. Benzodiazepine, a common tranquilizer, activates GABA receptors in our brains, including one set which encodes memories of fear-inducing events, storing them so that they are hidden from consciousness.
GABA receptors change how stressful events are encoded
As part of their new study, Dr. Radulovic’s team infused the hippocampus of mice with a drug known as gaboxadol, which stimulates extra-synaptic GABA receptors. The rodents were then placed in a box and given a brief, mild electrical shock. The next day, when the mice were put back in the same box, they moved about freely and showed no signs of fear.
These observations appeared to indicate that the mice didn’t recall the earlier shock that had taken place in that location. However, when the mice were put back on the drug and in the box, they appeared to be anticipating another shock. In short, once the mice were returned to the state in which they received the shock, they remembered the experience.
The findings reveal that when extra-synaptic GABA receptors were activated with the drug, they altered the way that the stressful event was encoded in the brains of the mice. When in the drug-induced state, their minds used completely different molecular pathways and neuronal circuits to store the memory than those utilized when they weren’t inebriated.
This system is regulated by a small microRNA, miR-33, and according to the authors, it may be the brain’s protective mechanism to deal with extremely stressful experiences. The results of this new study appears to indicate that some individuals will respond to traumatic stress by activating the extra-synaptic GABA system to store memories, thus making them essentially inaccessible.
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