” Memory is less of a video recording of the past, and more reconstructive,” says Ramirez, a BU College of Arts & & Sciences assistant professor of mental and brain sciences. It is both a blessing and a curse that memory is malleable in nature. If we remember false information, it is bad. Specifically for memories of something traumatic or scary, its excellent that our brains have the natural ability to mold and update memories to make them less potent.
What if its possible to use the malleable nature of our memories to our advantage, as a method to treat psychological health disorders like anxiety and trauma (PTSD)? Ramirez and his research group are actively pursuing this objective. And after years of studying memory in mice, theyve discovered not only where the brain stores positive and unfavorable memories, but likewise how to turn the volume down on unfavorable memories by artificially stimulating other, better ones.
” Our million-dollar concept is, what if a solution for some of these mental illness already exists in the brain? And what if memory is one way of getting there?” Ramirez asks. In 2 brand-new scientific papers, he and his team show the power of our psychological memories and how our experiences– and the method we process them– leave real physical footprints on the brain.
Mapping Positive and Negative Memories
One of the most important actions toward utilizing memory to deal with memory-related disorders is understanding where positive and unfavorable memories exist in the brain, and how to compare the two. Memories are saved in all various areas throughout the brain, and the private memories themselves exist as networks of cells called engrams. Ramirezs lab is especially thinking about the networks of memories located in the brains hippocampus, a cashew-shaped structure that shops sensory and psychological info crucial for forming and retrieving memories.
It may be tough to believe, however this is an image of a memory. In this image, the blue dots are favorable memory cells, and the red dots are negative memory cells. Memories exist in the brain as networks of cells called engrams, and are stored and processed all over the brain. The memories shown here lie in the hippocampus of a mouse. Credit: Photo by Stephanie Grella
Neuroscientists reveal that its possible to turn the volume down on an unfavorable memory by stimulating other, better ones.
Even though you might not recognize it, each time you recall a memory– such as your very first time riding a bike or strolling into your high school prom– your brain changes the memory ever so somewhat. Its almost like including an Instagram filter, with details being filled in and information being upgraded or lost with each recall.
” Were unintentionally using filters to our previous experiences,” says Steve Ramirez (CAS 10), a Boston University (BU) neuroscientist. Despite the fact that a filtered memory is various from the original, for the many part, you can inform what that basic picture is, he says.
In this image, the blue dots are positive memory cells, and the red dots are unfavorable memory cells. And after years of studying memory in mice, theyve found not only where the brain stores unfavorable and favorable memories, however likewise how to turn the volume down on negative memories by artificially stimulating other, better ones.
They can also color-code negative and favorable memories by inserting a fluorescent protein that is stimulated by light, so that positive memory cell networks glow green, for example, and unfavorable cell networks glow red or blue.
After artificially triggering another, more enjoyable memory, those red cells turned into the blue cells, which represent the altered, less powerful worry memory. The competing positive memory, according to the paper, upgraded the worry memory, minimizing the worry response at the time and long after the memory was triggered.
The term “engram” was created in 1904 by memory researcher Richard Semon. An engram is a system of cognitive info inscribed in a physical compound, thought to be the means by which memories are stored as biochemical or biophysical modifications in the brain or other biological tissue, in response to external stimuli.
In a new paper released in Nature Communications Biology, Ramirez, lead author Monika Shpokayte (MED 26), and a group of BU neuroscientists mapped out the crucial molecular and genetic distinctions between favorable and negative memories. They found that the two are in fact noticeably distinct on numerous levels. It ends up that emotional memories, like a favorable or negative memory, are physically distinct from other types of brain cells– and distinct from each other.
” Thats quite wild due to the fact that it recommends that these negative and positive memories have their own separate property in the brain,” states Ramirez, whos likewise a member of BUs Center for Systems Neuroscience.
The study authors found that negative and favorable memory cells are different from each other in practically every method– they are mainly saved in different areas of the hippocampus, they communicate with other cells utilizing various types of pathways, and the molecular equipment in both types of cells appears to be unique.
” So, theres [possibly] a molecular basis for distinguishing in between positive and negative memories in the brain,” Ramirez says. “We now have a bunch of markers that we understand separate favorable from negative in the hippocampus.”
Seeing and labeling unfavorable and positive memories is just possible with using an advanced neuroscience tool, called optogenetics. This is a way to fool brain cell receptors to react to light– scientists shine a safe laser light into the brain to switch on cells that have actually been provided a receptor that responds to light. They can likewise color-code favorable and unfavorable memories by inserting a fluorescent protein that is promoted by light, so that favorable memory cell networks glow green, for instance, and unfavorable cell networks glow red or blue.
In this image, the red cells are a worry memory. After synthetically triggering another, more enjoyable memory, those red cells turned into the blue cells, which represent the altered, less effective fear memory. This shows that the original memory has actually been altered by their memory manipulation technique, according to lead research study author Stephanie Grella Credit: Photo by Stephanie Grella.
Rewiring Bad Memories
Before the scientists label a memory in a mouse, they first need to make the memory. To do this, they expose the rodents to a unpleasant or universally good experience– a positive experience could be nibbling on some tasty cheese or fraternizing other mice; a negative experience could be getting a mild however surprising electrical shock to the feet. As soon as a new memory is formed, the researchers can find the network of cells that hang on to that experience, and have them radiance a specific color.
Once they can see the memory, researchers can utilize laser light to synthetically trigger those memory cells– and, as Ramirezs group has also found, reword the negative memories. In a paper released in Nature Communications, they discovered that synthetic activation of a positive experience completely rewrote an unfavorable experience, calling the emotional intensity of the bad memory down.
The scientists had the mice remember a negative experience, and throughout the worry memory recall, they artificially reactivated a group of favorable memory cells. The competing favorable memory, according to the paper, updated the fear memory, minimizing the worry reaction at the time and long after the memory was triggered. The research study constructs on previous work from Ramirezs laboratory that found its possible to synthetically control previous memories.
Activating a positive memory was the most powerful way to update an unfavorable memory, however the group also found its not the only way. Rather of targeting just positive memory cells, they also tried activating a neutral memory– some standard, boring experience for an animal– and after that tried activating the entire hippocampus, finding that both worked.
” If you stimulate a great deal of cells not always connected to any kind of memory, that can cause sufficient interference to disrupt the fear memory,” states Stephanie Grella, lead author and a previous postdoctoral fellow in the Ramirez Lab who just recently started the Memory & & Neuromodulatory Mechanisms Lab at Loyola University.
Although artificially activating memories is not possible to do in people, the findings could still translate to clinical settings, Grella states. “Because you can ask the individual, Can you remember something unfavorable, can you keep in mind something favorable?” she says– concerns you cant ask a mouse.
She suggests that it might be possible to bypass the effects of an unfavorable memory, one that has impacted an individuals frame of mind, by having a person remember the bad memory, and correctly timing a vibrant recall of a favorable one in a restorative setting.
” We understand that memories are flexible,” Grella states. “?? One of the things that we found in this paper was that the timing of the stimulation was really vital.”
The Quest for Game Changers
For other, more intensive types of treatment for extreme depression and PTSD, Grella recommends that it could ultimately be possible to stimulate large swaths of the hippocampus with tools like transcranial magnetic stimulation or deep brain stimulation– an intrusive procedure– to help individuals get rid of these memory-related disorders. Ramirez mentions that a growing number of neuroscientists have begun to embrace speculative treatments involving psychedelics and illegal drugs. A 2021 study discovered that regulated doses of MDMA helped relieve some serious PTSD signs.
” The theme here is utilizing some elements of benefit and positivity to reword the unfavorable elements of our past,” Ramirez states. “Its analogous to what were doing in rodents, other than in people– we synthetically activated favorable memories in rodents, and in humans, what they did was provide small dosages of MDMA to see if that could be enough to rewrite some of the distressing components of that experience.” These types of experiments point to the importance of continuing to check out the beneficial and medical methods of memory manipulation, but its crucial to keep in mind that these experiments were done under close medical guidance and shouldnt be attempted at house.
For now, Ramirez is delighted to see how this work can further press the boundaries in neuroscience, and wishes to see scientists experiment with much more out-of-the-box concepts that can change medication in the future: “We desire game changers, right?” he says. “We desire things that are going to be way more reliable than the presently available treatment choices.
Recommendations:
” Hippocampal cells segregate negative and positive engrams” by Monika Shpokayte, Olivia McKissick, Xiaonan Guan, Bingbing Yuan, Bahar Rahsepar, Fernando R. Fernandez, Evan Ruesch, Stephanie L. Grella, John A. White, X. Shawn Liu and Steve Ramirez, 26 September 2022, Communications Biology.DOI: 10.1038/ s42003-022-03906-8.
” Reactivating hippocampal-mediated memories throughout reconsolidation to disrupt fear” by Stephanie L. Grella, Amanda H. Fortin, Evan Ruesch, John H. Bladon, Leanna F. Reynolds, Abby Gross, Monika Shpokayte, Christine Cincotta, Yosif Zaki and Steve Ramirez, 12 September 2022, Nature Communications.DOI: 10.1038/ s41467-022-32246-8.
This work was supported by the National Institutes of Health.