Manipulating memory with light: Scientists erase specific memories in mice

Manipulating memory with light: Scientists erase specific memories in mice

  8:13:00 PM    Science Lover

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Just look into the light: not quite, but researchers at the UC Davis Center for Neuroscience and Department of Psychology have used light to erase specific memories in mice, and proved a basic theory of how different parts of the brain work together to retrieve episodic memories.

During memory retrieval, cells in the hippocampus
connect to cells in the brain cortex.

Credit: Photo illustration by Kazumasa Tanaka and 
Brian Wiltgen/UC Davis

Optogenetics, pioneered by Karl Diesseroth at Stanford University, is a new technique for manipulating and studying nerve cells using light. The techniques of optogenetics are rapidly becoming the standard method for investigating brain function.

Kazumasa Tanaka, Brian Wiltgen and colleagues at UC Davis applied the technique to test a long-standing idea about memory retrieval. For about 40 years, Wiltgen said, neuroscientists have theorized that retrieving episodic memories -- memories about specific places and events -- involves coordinated activity between the cerebral cortex and the hippocampus, a small structure deep in the brain.

"The theory is that learning involves processing in the cortex, and the hippocampus reproduces this pattern of activity during retrieval, allowing you to re-experience the event," Wiltgen said. If the hippocampus is damaged, patients can lose decades of memories.

But this model has been difficult to test directly, until the arrival of optogenetics.

Wiltgen and Tanaka used mice genetically modified so that when nerve cells are activated, they both fluoresce green and express a protein that allows the cells to be switched off by light. They were therefore able both to follow exactly which nerve cells in the cortex and hippocampus were activated in learning and memory retrieval, and switch them off with light directed through a fiber-optic cable.

They trained the mice by placing them in a cage where they got a mild electric shock. Normally, mice placed in a new environment will nose around and explore. But when placed in a cage where they have previously received a shock, they freeze in place in a "fear response."

Tanaka and Wiltgen first showed that they could label the cells involved in learning and demonstrate that they were reactivated during memory recall. Then they were able to switch off the specific nerve cells in the hippocampus, and show that the mice lost their memories of the unpleasant event. They were also able to show that turning off other cells in the hippocampus did not affect retrieval of that memory, and to follow fibers from the hippocampus to specific cells in the cortex.

"The cortex can't do it alone, it needs input from the hippocampus," Wiltgen said. "This has been a fundamental assumption in our field for a long time and Kazu’s data provides the first direct evidence that it is true."

They could also see how the specific cells in the cortex were connected to the amygdala, a structure in the brain that is involved in emotion and in generating the freezing response.

Co-authors are Aleksandr Pevzner, Anahita B. Hamidi, Yuki Nakazawa and Jalina Graham, all at the Center for Neuroscience. The work was funded by grants from the Whitehall Foundation, McKnight Foundation, Nakajima Foundation and the National Science Foundation.

Story Source:
The above story is based on materials provided by University of California - Davis. Note: Materials may be edited for content and length.

Journal Reference:
Kazumasa Z. Tanaka, Aleksandr Pevzner, Anahita B. Hamidi, Yuki Nakazawa, Jalina Graham, Brian J. Wiltgen. Cortical Representations Are Reinstated by the Hippocampus during Memory Retrieval. Neuron, 2014 DOI: 10.1016/j.neuron.2014.09.037

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Remembering to Forget: The Amnesic Effect of Daydreaming

Remembering to Forget: The Amnesic Effect of Daydreaming

  11:25:00 AM    Science Lover

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When your mind drifts, it's hard to remember what was going on before you stopped paying attention. Now a new study has found that the effect is stronger when your mind drifts farther -- to memories of an overseas vacation instead of a domestic trip, for example, or a memory in the more distant past.

When your mind drifts, it's hard to remember what was going on before you stopped paying attention. Now a new study has found that the effect is stronger when your mind drifts farther -- to memories of an overseas vacation instead of a domestic trip, for example, or a memory in the more distant past. (Credit: iStockphoto)

Psychologists have known for a while that context is important to remembering. If you leave the place where a memory was made -- its context -- it will be harder for you to recall the memory. Previous studies had also found that thinking about something else -- daydreaming or mind-wandering -- blocks access to memories of the recent past. Psychological scientists Peter F. Delaney and Lili Sahakyan of the University of North Carolina at Greensboro and Colleen M. Kelley and Carissa A. Zimmerman of Florida State University wanted to know if the content of your daydreams affects your ability to access a recently-acquired memory.

For one experiment, each participant looked at a list of words as they appeared on a computer screen, one at a time. Then they were told to think either about home -- where they'd been that morning -- or about their parents' house -- where they hadn't been in several weeks. Next, the participant was shown a second list of words. At the end of the test, they had to recall as many of the words from the two lists as possible. Participants who had thought about the place they'd been only a few hours before remembered more of the words from the first list than did participants who had thought back several weeks. The same was true for memories about place, tested in a second experiment. Those who thought about a vacation within the U.S. remembered more words than those who thought about a vacation abroad. The study is published in Psychological Science, a journal of the Association for Psychological Science.

One practical application of the research might be for people who want to forget about something. "If there's something you don't feel like thinking about, you're better off remembering a more distant event than a close event, to try to put it out of your mind for a while," says Delaney. "It can help you feel like you're in a different situation."

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Computer Algorithm Able to 'Read' Memories

Computer Algorithm Able to 'Read' Memories

  9:58:00 PM    Science Lover

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Computer programs have been able to predict which of three short films a person is thinking about, just by looking at their brain activity. The research, conducted by scientists at the Wellcome Trust Centre for Neuroimaging at UCL (University College London), provides further insight into how our memories are recorded.

To explore how memories are recorded, researchers showed volunteers three short films and asked them to memorize what they saw. The films were very simple, sharing a number of similar features -- all included a woman carrying out an everyday task in a typical urban street, and each film was the same length, seven seconds long. For example, one film showed a woman posting a letter. (Credit: Wellcome Trust Centre for Neuroimaging at UCL)

Professor Eleanor Maguire led this Wellcome Trust-funded study, an extension of work published last year which showed how spatial memories -- in that case, where a volunteer was standing in a virtual reality room -- are recorded in regular patterns of activity in the hippocampus, the area of the brain responsible for learning and memory.

"In our previous experiment, we were looking at basic memories, at someone's location in an environment," says Professor Maguire. "What is more interesting is to look at 'episodic' memories -- the complex, everyday memories that include much more information on where we are, what we are doing and how we feel."

To explore how such memories are recorded, the researchers showed ten volunteers three short films and asked them to memorise what they saw. The films were very simple, sharing a number of similar features -- all included a woman carrying out an everyday task in a typical urban street, and each film was the same length, seven seconds long. For example, one film showed a woman drinking coffee from a paper cup in the street before discarding the cup in a litter bin; another film showed a (different) woman posting a letter.

The volunteers were then asked to recall each of the films in turn whilst inside an fMRI scanner, which records brain activity by measuring changes in blood flow within the brain.

A computer algorithm then studied the patterns and had to identify which film the volunteer was recalling purely by looking at the pattern of their brain activity. The results are published in the journal Current Biology.

"The algorithm was able to predict correctly which of the three films the volunteer was recalling significantly above what would be expected by chance," explains Martin Chadwick, lead author of the study. "This suggests that our memories are recorded in a regular pattern."

Although a whole network of brain areas support memory, the researchers focused their study on the medial temporal lobe, an area deep within the brain believed to be most heavily involved in episodic memory. It includes the hippocampus -- an area which Professor Maguire and colleagues have studied extensively in the past.

They found that the key areas involved in recording the memories were the hippocampus and its immediate neighbours. However, the computer algorithm performed best when analysing activity in the hippocampus itself, suggesting that this is the most important region for recording episodic memories. In particular, three areas of the hippocampus -- the rear right and the front left and front right areas -- seemed to be involved consistently across all participants. The rear right area had been implicated in the earlier study, further enforcing the idea that this is where spatial information is recorded. However, it is still not clear what role the front two regions play.

"Now that we are developing a clearer picture of how our memories are stored, we hope to examine how they are affected by time, the ageing process and by brain injury," says Professor Maguire.

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Surprise! Neural Mechanism May Underlie an Enhanced Memory for the Unexpected

Surprise! Neural Mechanism May Underlie an Enhanced Memory for the Unexpected

  9:06:00 AM    Science Lover

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The human brain excels at using past experiences to make predictions about the future. However, the world around us is constantly changing, and new events often violate our logical expectations.

The element of surprise appears to have a big effect on our ability to remember. Researchers have discovered that unexpected stimuli enhanced an early and a late electrical potential in the hippocampus and the late signal was associated with a memory for the unexpected picture. (Credit: iStockphoto/Rosemarie Gearhart)

"We know these unexpected events are more likely to be remembered than predictable events, but the underlying neural mechanisms for these effects remain unclear," says lead researcher, Dr. Nikolai Axmacher, from the University of Bonn in Germany.

Dr. Axmacher and colleagues, whose new study is published by Cell Press in the February 25 issue of the journal Neuron, investigated the relationship between novelty processing and memory formation in two key brain structures, the hippocampus, and the nucleus accumbens. The hippocampus plays a key role in memory formation while the nucleus accumbens is involved in processing rewards and novel information. Previous work had suggested that information transfer between these structures may be associated with enhanced memory for unexpected items or events.

Obtaining direct information on the electrical activity of these structures deep in the brain is usually impossible in humans. However, the researchers used the opportunity to record from two groups of patients with electrodes implanted in these regions: Epilepsy patients awaiting surgical treatment of severe epilepsy, and patients with treatment-resistant depression undergoing deep-brain stimulation. Both groups of participants studied pictures of faces and houses in grayscale that were usually presented on a red or green background, respectively. Occasionally, a picture would have an "unexpected" configuration, such as a face on a green background. Subjects were subsequently tested for their memory of the expected and unexpected items.

The researchers discovered that unexpected stimuli enhanced an early and a late electrical potential in the hippocampus and the late signal was associated with a memory for the unexpected picture. In the nucleus accumbens, there was only a late potential which was larger during exposure to unexpected items. "Our findings support the idea that hippocampal activity may initially signal the occurrence of an unexpected event and that the nucleus accumbens may influence subsequent processing which serves to promote memory encoding," explains Dr. Axmacher.

The authors are careful to point out that one limitation of their study is that the recordings from the hippocampus and nucleus accumbens came from two separate groups of subjects, so their data provide an indirect measure of the functional connectivity between these two brain areas. However, their findings do provide fascinating new insight into this complex brain circuit. "Taken together, these are the first results that speak to the relative timing of expectation effects in different regions of the human brain, and they support models of accumbens-hippocampus interactions during encoding of unexpected events," concludes Dr. Axmacher.

The researchers include Nikolai Axmacher, University of Bonn, Bonn, Germany, University of California, Davis, Davis, CA; Michael X. Cohen, University of Amsterdam, Amsterdam, The Netherlands, University of Arizona, Tucson, AZ; Juergen Fell, University of Bonn, Bonn, Germany; Sven Haupt, University of Bonn, Bonn, Germany; Matthias Dumpelmann, Epilepsy Center, University Hospital Freiburg, Freiburg, Germany; Christian E. Elger, University of Bonn, Bonn, Germany, University of California, Davis, Davis, CA; Thomas E. Schlaepfer, University of Bonn, Bonn, Germany, The Johns Hopkins University, Baltimore, MD; Doris Lenartz, University of Cologne, Koln, Germany; Volker Sturm, University of Cologne, Koln, Germany; and Charan Ranganath, University of California, Davis, Davis, CA.

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Scientists Decode Memory-Forming Brain Cell Conversations

Scientists Decode Memory-Forming Brain Cell Conversations

  12:37:00 AM    Science Lover

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The conversations neurons have as they form and recall memories have been decoded by Medical College of Georgia scientists.

Artist's rendering of neurons. (Credit: iStockphoto)

The breakthrough in recognizing in real time the formation and recollection of a memory opens the door to objective, thorough memory studies and eventually better therapies, said Dr. Joe Tsien, neuroscientist and co-director of MCG's Brain & Behavior Discovery Institute. He is corresponding author on the study published Dec. 16 in PLoS ONE.

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How We Know A Dog Is A Dog: Concept Acquisition In The Human Brain

How We Know A Dog Is A Dog: Concept Acquisition In The Human Brain

  10:35:00 AM    Science Lover

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A new study explores how our brains synthesize concepts that allow us to organize and comprehend the world. The research, published by Cell Press in the September 24th issue of the journal Neuron, uses behavioral and neuroimaging techniques to track how conceptual knowledge emerges in the human brain and guides decision making.

Although two dogs can look very different, the human brain recognizes them as particular instances of the concept of a dog. (Credit: iStockphoto/Annette Wiechmann)







The ability to use prior knowledge when dealing with new situations is a defining characteristic of human intelligence. This is made possible through the use of concepts, which are formed by abstracting away the common essence from multiple distinct but related entities. "Although a Poodle and a Golden Retriever look very different from each other, we can easily appreciate their similar attributes because they can be recognized as instances of a particular concept, in this case a dog," explains lead study author, Dr. Dharshan Kumaran from the Wellcome Trust Centre for Neuroimaging at University College London.

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Scientists erase bad memories from brain

Scientists erase bad memories from brain

  2:01:00 AM    Science Lover

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It may soon be possible to erase bad memories from the human brain.

Canadian scientists at the University of Toronto and the local Hospital for Sick Children have found a link between a given memory and specific neurons - the cells in the brain that transmit information - that store it.

The human brain has over 100 billion neurons, but memories are stored in only small number of them. Scientists have been trying to identify these precise neurons that encode a given memory.

Now in their experimental study on mice (which has 100 million neurons), the Toronto research team has succeeded in identifying precise neurons that carry a particular memory.

Unlike in the past when scientists had deleted an entire brain region in mice to try and erase a memory in the hopes of finding out about how memories are normally stored, the Toronto team has succeeded in removing only the small portion of neurons that stored a specific memory.

"Though previous studies have provided important evidence suggesting that specific neurons are involved in a memory, we believe this (study) paper is the first to establish causal links," a university statement quoted study leader and physiology professor Sheena Josselyn as saying.

In their previous experiments, the same research team had found evidence that in mice, fear memories are stored in specific neurons within a brain structure known as the lateral amygdala (LA) that have a high amount of a specific protein (CREB).

This means that CREB levels helps dictate which neurons are involved in storing a memory.

Now in their latest study, the research team destroyed only these LA neurons with high levels of CREB and found that mice no longer remembered the fearful event. The research team also showed that random removal of any LA neurons does not erase the fear memory. You have to remove only specific set of neurons that store a memory.

"Our experiences, both good and bad, teach us things," said study leader Josselyn.

"If we did not remember that the last time we touched a hot stove we got burned, we would be more likely to do it again. So in this sense, even memories of bad or frightening experiences are useful.

"However, there are some cases in which fearful memories become maladaptive, such as with post-traumatic stress disorder or severe phobia. Selectively erasing these intrusive memories may improve the lives of afflicted individuals," she said.

"Our studies suggest that one strategy would be to target interventions to that small subset of neurons actually involved in storing a memory, rather than the entire brain. It sounds like a futuristic film, but our results in mice do provide proof-of-principle that this may one day be possible in humans," said co-researcher Paul Frankland.

The study is published in the March 13 issue of the journal Science.

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