It may be tough to think, however this is an image of a memory. In this image, the blue dots are favorable memory cells, and the red dots are unfavorable memory cells. Memories exist in the brain as networks of cells called engrams, and are saved and processed all over the brain. The memories revealed here lie in the hippocampus of a mouse. Credit: Photo by Stephanie Grella
Neuroscientists reveal that it’s possible to turn the volume down on an unfavorable memory by promoting other, better ones.
Even though you might not understand it, each time you remember a memory– such as your very first time riding a bike or strolling into your high school senior prom– your brain alters the memory ever so somewhat. It’s nearly like including an Instagram filter, with information being completed and info being upgraded or lost with each recall.
“We’re inadvertently applying filters to our past experiences,” states Steve Ramirez (CAS’10), a Boston University (BU) neuroscientist. Even though a filtered memory is various from the initial, for the a lot of part, you can inform what that standard image is, he states.
“Memory is less of a video recording of the past, and more reconstructive,” states Ramirez, a BU College of Arts & &(******************************************************************************************************************************* )assistant teacher of mental and brain sciences. It is both a true blessing and a curse that memory is flexible in nature. If we keep in mind incorrect information, it is bad. However, specifically for memories of something frightening or terrible, it’s excellent that our brains have the natural capability to mold and upgrade memories to make them less powerful.
What if it’s possible to utilize the flexible nature of our memories to our benefit, as a method to treat psychological health conditions like anxiety and trauma (< period class ="glossaryLink" aria-describedby ="tt" data-cmtooltip ="<div class=glossaryItemTitle>PTSD</div><div class=glossaryItemBody>Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops in some people who have experienced or witnessed a shocking, scary, or dangerous event.</div>" data-gt-translate-attributes="[{" attribute="">PTSD)? Ramirez and his research team are actively pursuing this goal. And after years of studying memory in mice, they’ve found not only where the brain stores positive and negative memories, but also how to turn the volume down on negative memories by artificially stimulating other, happier ones.
“Our million-dollar idea is, what if a solution for some of these mental disorders already exists in the brain? And what if memory is one way of getting there?” Ramirez asks. In two new scientific papers, he and his team demonstrate the power of our emotional memories and how our experiences—and the way we process them—leave actual physical footprints on the brain.
Mapping Positive and Negative Memories
One of the most important steps toward using memory to treat memory-related disorders is understanding where positive and negative memories exist in the brain, and how to distinguish between the two. Memories are stored in all different areas across the brain, and the individual memories themselves exist as networks of cells called engrams. Ramirez’s lab is particularly interested in the networks of memories located in the brain’s hippocampus, a cashew-shaped structure that stores sensory and emotional information important for forming and retrieving memories.
The term “engram” was coined in 1904 by memory researcher Richard Semon. An engram is a unit of cognitive information imprinted in a physical substance, theorized to be the means by which memories are stored as biophysical or biochemical changes in the brain or other biological tissue, in response to external stimuli.
In a new paper published in Nature Communications Biology, Ramirez, lead author Monika Shpokayte (MED’26), and a team of BU neuroscientists mapped out the key molecular and genetic differences between positive and negative memories. They found that the two are actually strikingly distinct on multiple levels. It turns out that emotional memories, like a positive or negative memory, are physically distinct from other types of brain cells—and distinct from each other.
“That’s pretty wild because it suggests that these positive and negative memories have their own separate real estate in the brain,” says Ramirez, who’s also a member of BU’s Center for Systems Neuroscience.
The study authors found that positive and negative memory cells are different from each other in almost every way—they are mostly stored in different regions of the hippocampus, they communicate with other cells using different types of pathways, and the molecular machinery in both types of cells seems to be distinct.
“So, there’s [potentially] a molecular basis for separating in between favorable and unfavorable memories in the brain,” Ramirez states. “We now have a bunch of markers that we know differentiate positive from negative in the hippocampus.”
Seeing and identifying favorable and unfavorable memories is just possible with using a sophisticated neuroscience tool, called optogenetics. This is a method to deceive brain cell receptors to react to light– scientists shine a safe laser light into the brain to switch on cells that have actually been offered a receptor that reacts to light. They can likewise color-code favorable and unfavorable memories by placing a fluorescent protein that is promoted by light, so that favorable memory cell networks radiance green, for instance, and unfavorable cell networks radiance red or blue.
In this image, the red cells are a worry memory. After synthetically triggering another, more enjoyable memory, those red cells developed into the blue cells, which represent the transformed, less effective worry memory. This shows that the initial memory has actually been changed by their memory control method, according to lead research study author StephanieGrella Credit: Photo by Stephanie Grella
Rewiring Bad Memories
Before the scientists identify a memory in a mouse, they initially need to make the memory. To do this, they expose the rodents to a generally excellent or undesirable experience– a favorable experience might be munching on some delicious cheese or fraternizing other mice; an unfavorable experience might be getting a moderate however unexpected electrical shock to the feet. Once a brand-new memory is formed, the researchers can discover the network of cells that hang on to that experience, and have them radiance a particular color.
Once they can see the memory, scientists can utilize laser light to synthetically trigger those memory cells– and, as Ramirez’s group has actually likewise found, reword the unfavorable memories. In a paper released in Nature Communications, they discovered that synthetic activation of a favorable experience completely reworded an unfavorable experience, calling the psychological strength of the bad memory down.
The scientists had the mice remember an unfavorable experience, and throughout the worry memory recall, they synthetically reactivated a group of favorable memory cells. The contending favorable memory, according to the paper, upgraded the worry memory, minimizing the worry action at the time and long after the memory was triggered. The research study constructs on previous work from Ramirez’s laboratory that discovered it’s possible to synthetically control previous memories.
Activating a favorable memory was the most effective method to upgrade an unfavorable memory, however the group likewise discovered it’s not the only method. Instead of targeting simply favorable memory cells, they likewise attempted triggering a neutral memory– some basic, dull experience for an animal– and after that attempted triggering the entire hippocampus, discovering that both worked.
“If you stimulate a lot of cells not necessarily tied to any type of memory, that can cause enough interference to disrupt the fear memory,” states Stephanie Grella, lead author and a previous postdoctoral fellow in the Ramirez Lab who just recently began the Memory & & Neuromodulatory Mechanisms Lab at Loyola University.
Even though synthetically triggering memories is not possible to do in human beings, the findings might still equate to medical settings, Grella states. “Because you can ask the person, ‘Can you remember something negative, can you remember something positive?’” she states– concerns you can’t ask a mouse.
She recommends that it might be possible to bypass the effects of an unfavorable memory, one that has actually impacted an individual’s mindset, by having an individual remember the bad memory, and properly timing a vibrant recall of a favorable one in a restorative setting.
“We know that memories are malleable,” Grella states. “??One of the things that we found in this paper was that the timing of the stimulation was really critical.”
The Quest for Game Changers
For other, more extensive kinds of treatment for serious anxiety and PTSD, Grella recommends that it might become possible to promote big swaths of the hippocampus with tools like transcranial magnetic stimulation or deep brain stimulation– an intrusive treatment– to assist individuals get rid of these memory-related conditions. Ramirez explains that increasingly more neuroscientists have actually begun to accept speculative treatments including psychedelics and illegal drugs. For example, a 2021 research study discovered that regulated dosages of MDMA assisted ease some serious PTSD signs.
“The theme here is using some aspects of reward and positivity to rewrite the negative components of our past,” Ramirez states. “It’s analogous to what we’re doing in rodents, except in humans—we artificially activated positive memories in rodents, and in humans, what they did was give them small doses of MDMA to see if that could be enough to rewrite some of the traumatic components of that experience.” These kinds of experiments indicate the significance of continuing to check out the medical and advantageous approaches of memory control, however it is essential to keep in mind that these experiments were done under close medical guidance and should not be tried in the house.
For now, Ramirez is thrilled to see how this work can even more press the borders in neuroscience, and wishes to see scientists try out much more out-of-the-box concepts that can change medication in the future: “We want game changers, right?” he states. “We desire things that are going to be way more reliable than the presently readily available treatment choices.
References:
“Hippocampal cells segregate favorable and unfavorable 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 during 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.
