Investigators identify neural circuit, genetic 'switch' that maintain memory precisionMarch 12, 2018
Investigators from the Massachusetts General Hospital (MGH) Center for Regenerative Medicine and the Harvard Stem Cell Institute (HSCI) have identified a neural circuit mechanism involved in preserving the specificity of memories. They also identified a genetic 'switch' that can slow down memory generalization - the loss of specific details over time that occurs in both age-related memory impairment and in post-traumatic stress disorder, in which emotions originally produced by traumatic experiences are elicited in response to innocuous cues that have little resemblance to the traumatic memory.
"The circuit mechanism we identified in mice allows us to preserve the precision or the details of memories over the passage of time in adult as well as aged animals," says Amar Sahay, PhD, of the MGH Center for Regenerative Medicine and HSCI, corresponding author of a paper appearing in Nature Medicine. "These findings have implications for the generalization of traumatic memories in PTSD and for memory imprecision in aging."
Memories are generated in the seahorse-shaped brain structure called the hippocampus and stored in the prefrontal cortex at the front of the brain. Memory formation involves cells in a portion of the hippocampus called the dentate gyrus, and memories are thought to be conveyed to the prefrontal cortex via the CA subregions of the hippocampus, specifically subregions CA3 and CA1. The hippocampus also is believed to play a continuing role in the stabilization of memories in the cortex - maintaining the precise details that keep one memory from being confused with another and preventing issues ranging from not being able to remember dinner selections from a week ago to age-related memory issues.
Hyperactivity of this hippocampal circuitry has been observed in aged animals - rodents, non-human primates and humans - and alterations in hippocampal structure are seen in patients with PTSD. The current study was designed to investigate the hypothesis that inhibitory signals passing from dentate gyrus cells (DGCs) to the CA3 subregion help to constrain hyperactivity and maintain the stability and precision of memories over time.
A key finding by Sahay's team was identification of a protein called abLIM3 - highly expressed in DGCs but absent in the CA field of mouse brains - that acts as a molecular brake on the inhibitory signals DGCs exert onto the CA3 subregion. Experimental manipulation of abLIM3 levels in DGCs in adult mice revealed that decreasing abLIM3 levels increased the delivery of inhibitory signals to CA3 neurons. A series of experiments with mouse models showed that manipulation of abLIM3 levels within DGCs could slow down the process of memory generalization.
Using a classical behavioral conditioning protocol, the investigators first trained the animals to expect an unpleasant sensation, a mild but not painful foot shock, in a particular context, such as being placed into a box with dark walls. Typically, when animals are placed in the same context, they will 'freeze' in expectation of the shock but will do not react to a context not associated with the shock, such as a box with light walls. But after two weeks, the memory will generalize and the animals will 'freeze' when place in any context, even one with little resemblance to that in which they received the foot shock.
In contrast, decreasing abLIM3 levels within DGCs maintained the specificity of the memory over time so that, even two weeks later, the mice would only freeze when placed into the foot-shock associated context. The investigators also found that decreasing abLIM3 levels in aged mice reversed age-related alterations in DGC-CA3 circuitry and improved memory precision. A recent study by another group found significantly increased abLIM3 levels in the circulation of aged humans who are beginning to show signs of memory impairment.
"Our ability to improve memory precision in both adult and aged mice by essentially 'flipping a genetic switch' suggests that targeting abLIM3 expression in DGCs may lead to similar improvement in aged humans, a strategy we are actively pursuing," says Sahay, who is an associate professor of Psychiatry at Harvard Medical School and principal faculty of the Harvard Stem Cell Institute. "Since overgeneralization of traumatic memories is a hallmark of PTSD, we are also keen to assess abLIM3 levels in patients with PTSD and investigate whether reducing abLIM3 expression could prevent the activation of traumatic memories."
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."
Massachusetts General Hospital
Related Memory Articles:
A quick glance at any social media platform will tell you that people love taking photos of their experiences -- whether they're lying on the beach, touring a museum, or just waiting in line at the grocery store.
Research from Katherine Duncan at the University of Toronto suggests we may have to rethink how we improve memory.
The ability to remember sounds, and manipulate them in our minds, is incredibly important to our daily lives -- without it we would not be able to understand a sentence, or do simple arithmetic.
In the battle of the sexes, women have long claimed that they can remember things better and longer than men can.
A collaboration between Universitat Autònoma de Barcelona and Harvard University pioneers the increase of memory using optogenetics in mice in Spain.
Peppermint tea can improve long-term and working memory and in healthy adults.
MIT study finds bursts of neural activity as the brain holds information in mind, overturns a long-held model.
For over forty years, neuro-scientists have been interested in the biological mechanisms underlying the storage of the information that our brain records every day.
Why is it that some people have richly detailed recollection of past experiences (episodic memory), while others tend to remember just the facts without details (semantic memory)?
Neuroscientists at Rosalind Franklin University of Medicine and Science have discovered a novel mechanism for memory formation.
Related Memory Reading:
Unlimited Memory: How to Use Advanced Learning Strategies to Learn Faster, Remember More and be More Productive
by Kevin Horsley (Author)
Kevin Horsley Broke a World Memory Record in 2013...
And You're About to Learn How to Use His Memory Strategies to Learn Faster, Be More Productive and Achieve More Success
Most people never tap into 10% of their potential for memory. In this book, you're about to learn:
How the World's Top Memory Experts Concentrate and Remember Any Information at Will, and How You Can Too
Do you ever feel like you're too busy, too stressed or just too distracted to concentrate and get work done? In Unlimited Memory, you'll learn how the world's best memory masters... View Details
The Memory Book: The Classic Guide to Improving Your Memory at Work, at School, and at Play
by Harry Lorayne (Author), Jerry Lucas (Author)
Unleash the hidden power of your mind through Harry Lorayne and Jerry Lucas's simple, fail-safe memory system, and you can become more effective, more imaginative, and more powerful, at work, at school, in sports and play. Discover how easy it is to: file phone numbers, data, figures, and appointments right in your head; learn foreign words and phrases with ease; read with speed--and greater understanding; shine in the classroom--and shorten study hours; dominate social situations, and more.
From the Paperback edition. View Details
Moonwalking with Einstein: The Art and Science of Remembering Everything
by Joshua Foer (Author)
The blockbuster phenomenon that charts an amazing journey of the mind while revolutionizing our concept of memory
An instant bestseller that is poised to become a classic, Moonwalking with Einstein recounts Joshua Foer's yearlong quest to improve his memory under the tutelage of top "mental athletes." He draws on cutting-edge research, a surprising cultural history of remembering, and venerable tricks of the mentalist's trade to transform our understanding of human memory. From the United States Memory Championship to deep within the author's own mind, this is an... View Details
Memory Man (Memory Man series)
by David Baldacci (Author)
With over 110 million copies of his novels in print, David Baldacci is one of the most widely read storytellers in the world. Now he introduces a startling, original new character: a man with perfect memory who must solve his own family's murder.
Amos Decker's life changed forever--twice.
The first time was on the gridiron. A big, towering athlete, he was the only person from his hometown of Burlington ever to go pro. But his career ended before it had a chance to begin. On his very first play, a violent helmet-to-helmet collision knocked him off the... View Details
Memory Rescue: Supercharge Your Brain, Reverse Memory Loss, and Remember What Matters Most
by Daniel G. Amen (Author)
A proven program from #1 New York Times bestselling author and brain researcher Dr. Daniel Amen to help you change your brain and improve your memory today!
Brain imaging research demonstrates that memory loss actually starts in the brain decades before you have any symptoms. Learn the actions you can take to help not just prevent memory loss later in life . . . but to begin restoring the memory you may have already lost.
Expert physician Dr. Amen reveals how a multipronged strategy―including dietary changes, physical and mental exercises, and spiritual... View Details
Memory (Miles Vorkosigan Adventures)
by Lois McMaster Bujold (Author)
Restored to life after being pronounced dead, Miles Vorkosigan realizes that the event has left him with a profound weakness and is dismissed from his job, but things are further complicated when he remembers something he saw while dead. Reprint. View Details
In Search of Memory: The Emergence of a New Science of Mind
by Eric R. Kandel (Author)
“A stunning book.”―Oliver SacksMemory binds our mental life together. We are who we are in large part because of what we learn and remember. But how does the brain create memories? Nobel Prize winner Eric R. Kandel intertwines the intellectual history of the powerful new science of the mind―a combination of cognitive psychology, neuroscience, and molecular biology―with his own personal quest to understand memory. A deft mixture of memoir and history, modern biology and behavior, In Search of Memory brings readers from Kandel's childhood in... View Details
The Seven Sins of Memory: How the Mind Forgets and Remembers
by Daniel L. Schacter (Author)
A groundbreaking work by one of the world's foremost psychologists that delves into the complex behavior of memory.
In this fascinating study, Daniel L. Schacter explores instances of what we would consider memory failure—absent-mindedness, transience, blocking, misattribution, suggestibility, bias, and persistence—and suggests instead that these miscues are actually indications that memory is functioning as designed. Drawing from vivid scientific research and creative literature, as well as high-profile events in which memory has figured significantly (Bill... View Details
How to Develop a Brilliant Memory Week by Week: 50 Proven Ways to Enhance Your Memory Skills
by Dominic O'Brien (Author)
Written by eight times World Memory Champion, Dominic O'Brien this book is a complete course in memory enhancement. Dominic takes you step-by-step through an ingenious program of skills, introducing all his tried and tested techniques on which he has built his triumphant championship performances. Pacing the course in line with his expert understanding of how the brain responds to basic memory training, Dominic offers strategies and tips that will expand your mental capacities at a realistic but impressive rate. View Details
Memory Improvement: How to Improve Your Memory in Just 30 Days
by Gildan Media, LLC
Have you ever walked into a room and couldn't remember what you went there for? Have you ever grasped the hand of a potential client and then when the handshake broke, the name seemed to disappear from your memory? Or have you ever left a prospect or an important meeting and as you drove away remembered a key point that you should have shared with them?
The problem is NOT with your memory. The problem is with the "Filing System" your brain currently uses to store and retrieve memory items. Change the filing system and you'll double and even triple your memory comprehension.... View Details