Gut feelings may actually reflect reliable memories

We've had a bit of discussion of "gut feelings" recently. See here, here.

I've thought for a long time that one explanation of "intuition" and "gut feelings" when applied to dealing with a particular issue or problem is that we have dealt with a similar issue or problem before, but we do not have a clear memory of having done so. Or else we have read or otherwise learned some information related to the issue or problem. But when confronted with the issue or problem again, we "intuitively" sense how to deal with it, even though we aren't conscious of remembering the previous experience or information.

Actually, this happens a lot with experts in many areas, such as law, medicine, or business. For example, a young physician examining a patient with a certain set of symptoms may recall having learned in school that the symptoms might indicate any of several different problems. And that to distinguish among the possible causes of the symptoms it is necessary to carefully examine the particulars of the situation.

An older, more experienced physician, on the other hand, may quickly settle on one specific diagnosis without consciously going over the detailed checklist of distinguishing indicators. In this latter case, the "intuition" may simply be unconscious recollection of past experience where some specific feature in the symptoms correctly tipped the balance between one diagnosis or another.

This is not an original observation (though I can't quite recall where I first saw it), but there is new research that does support it:

Gut Feelings May Actually Reflect Reliable Memories (2/8/09)

You know the feeling. You make a decision you're certain is merely a "lucky guess."

A new study from Northwestern University offers precise electrophysiological evidence that such decisions may sometimes not be guesswork after all.

The research utilizes the latest brain-reading technology to point to the surprising accuracy of memories that can't be consciously accessed.

During a special recognition test, guesses turned out to be as accurate or more accurate than when study participants thought they consciously remembered.

"We may actually know more than we think we know in everyday situations, too," said Ken Paller, professor of psychology at Northwestern.

Actually, this is so well known that psychologists have names for it: "implicit memory" or "recognition memory". It's closely related to another effect called "priming".

So when we are, sometimes, urged to go with our intuition or "gut feelings" in making a decision, it's not necessarily bad advice. We may in fact be making well-informed decisions even when we think we are using our "intuition". But the problem is that our memory, whether explicit or implicity, can be unreliable or downright wrong. So "intuition" can just as easily get us into trouble.

In particular, we may be remembering "information" that is simply untrue. As Satchel Paige is reported to have said, "It's not what you don't know that hurts you. It's what you know that just ain't so."

When faced with important decisions, and enough time to consider them, perhaps it's not a bad idea to go consult reliable sources of information, just to be sure...

The blog Neurophilosophy has a good discussion of this research and implicit memory:

The neurological basis of intuition (2/9/09)

Most of us have experienced the vague feeling of knowing something without having any memory of learning it. This phenomenon is commonly known as a "gut feeling" or "intuition"; more accurately though, it is described as implicit or unconscious recognition memory, to reflect the fact that it arises from information that was not attended to, but which is processed, and can subsequently be retrieved, without ever entering into conscious awareness.

Further reading:

Study Suggests Why Gut Instincts Work (2/8/09) – Livescience.com

Hidden memories guide choices (2/9/09) – Nature.com

Subliminal messages really do affect your decisions (2/14/09) – NewScientist.com

Tags: intuition, implicit memory

Memory and BDNF

Following up on part of this note, where I discussed relationships between memory and stress, it turns out that there are some interesting things known, related to this, which involve a "neurotrophic factor" called BDNF.

In fact, there's quite a lot to say. Let's begin with an explanation of some terms, a little about BDNF, and a look at some research from the past several years on the relationship between BDNF and memory. Later we'll take up more on how stress and depression enter the picture.

A neurotrophin is a type of protein that promotes the survival of neurons – which is in general a pretty good thing. (We'll get to examples in a moment.) One type of neurotrophin, known as a "neutotropic factor", is a growth factor that affects neurons in particular.

More generally, a growth factor is a proteins that signals certain types of cells to survive, differentiate, or grow. A growth factor that helps a cell survive does so by inhibiting programmed cell death. Other growth factors promote cell division, which results in growth of the tissue that contains the affected cells. Yet other growth factors may induce cells to differentiate into cells of a more specialized type.

An important example of a general growth factor is IGF-1, also known as "insulin-like growth factor 1", which we'll be looking at more extensively in upcoming posts.

In this post we're going to consider the specific neurotrophic factor known as BDNF, the brain-derived neurotrophic factor.

Research has shown that BDNF plays a role in memory formation and in the connection between stress and depression. For example, in rats the stress hormone corticosterone seems to decrease the expression of BDNF, and if stress is persistent, this eventually leads to the atrophy of the hippocampus. Since the hippocampus plays an important role in long term memory, this is one way in which stress can negatively impact memory.

Atrophy of the hippocampus has also been found in humans suffering from chronic depression. There is evidence that suggests a deficiency of BDNF may be at least in part implicated in such depression. For example, various factors (such as the neurotransmitter glutamate, exercise, calorie restriction, and antidepressant drugs) are known to stimulate expression of BDNF – and often ameliorate depression as well.

There's a lot of science behind all this. Let's just look at a few research announcements from the past several years to get a feel for the interactions of BDNF and memory.

Key Pathway In Synaptic Plasticity Discovered (5/23/07)

The researchers studied a major developmental event in newborn rodents. A rapid increases in synapse strength and visual circuit refinement occurs quickly after the animal's eyes first open. It was already known that the PSD-95 protein rushes to visual system synapses soon after eye opening. PSD-95 is a scaffold protein that anchors several types of receptors. Some of these receptors are for the neurotransmitter glutamate, and there is also the TrkB receptor for BDNF (and other neurotrophins).

A positive feedback loop is initiated, in which the NMDA glutamate receptor activates BDNF. BDNF then triggers a signaling pathway involving the kinases PI3 and Akt. This pathway leads to more PSD-95 production, completing the loop. The net result is to make synapses more responsive to BDNF, followed by production of additional PSD-95. Once this loop is started at just a few of a neuron's synapses, the rush of PSD-95 to other excitory synapses of the neuron is on. In this way a few very active synapses can prime larger regions of a neuron for long-term synaptic strengthening in response to subsequent stimulation in the newborn animal.

Proteins Necessary For Brain Development Found To Be Critical For Long-term Memory (9/5/06)

This research indicates that BDNF, which is crucial for the growth of brain cells during development, is also equally important for the formation of long-term memories. The study was performed on the common marine snail Aplysia. When the snails are electrically shocked, the neurotransmitter serotonin is released and promotes the formation of long-term memories associated with the shocks. But when the researchers blocked interaction between BDNF and its TrkB receptor, long-term memories did not form, even though serotonin was still released at synapses. This indicates that serotonin alone was not sufficient for long-term memory formation. Short-term memory formation was not affected. Further investigation showed that interfering with the BDNF receptors blocked long-term enhancement of the connections between the brain cells in the reflex circuit normally induced by the shock treatment.

Drug Triggers Body's Mechanism To Reverse Aging Effect On Memory Process (7/27/06)

A class of drugs known as "ampakines" (so-called because they target AMPA receptors) has been under study and development since the early 1990s to deal with neurological conditions, such as schizophrenia, problems of attention span and alertness, and memory impairment associated with dementia and Alzheimer's disease. The research reported here was conducted by a team that included Gary Lynch, who has long been associated with investigation of the biological bases of learning and memory. (See here for more about Lynch and long-term memory.)

In this study, rats were treated for four days with an ampakine drug. Of particular interest was the effect of the drug on the hippocampus of the brain, because of its known importance in the formation of long-term memories. In the hippocampus areas of rats treated with the drug, it was found that (compared to controls) there was a significant increase both of levels of BDNF and of long-term potentiation (LTP) of synapses (an indicator of memory formation). Further, even though the drug had a known half-life of only 15 minutes, elevated levels of BDNF and LTP were observed as long as 18 hours after drug administration was stopped.

Tiny RNA Molecules Fine-tune The Brain's Synapses (1/24/06)

Synapses between two neurons are formed between locations at the tip of an axon of one neuron (the "presynaptic" neuron) and a dendrite on the body of another neuron (the "postsynaptic" neuron). In order to form a complete synapse, it is necessary for there to be protrusions called "dendritic spines" on dendrites of the postsynaptic neuron. In the process of synaptic signaling, it is these spines that absorb neurotransmitter molecules released by the axon of the presynaptic neuron. Consequently, any mechanism that affects the density of spines on dendrites will affect the total number of synapses that can form between neurons.

It had previously been established that BDNF activates a protein kinase called Limk1, which in turn promotes the growth of dendritic spines and hence the ability of synapses to form. This research on rats studied the effect of the microRNA miR-134 on growth of dendritic spines of hippocampal neurons. It was found that when neurons were exposed to miR-134, spine volume significantly decreased, and synapses weakened. Conversely, when miR-134 was inhibited, spines increased in size, strengthening synapses. However, increased levels of BDNF negated the effects of miR-134, indicating that miR-134 achieved its effect by suppressing Limk1.

More: Spine control

Tags: BDNF, memory

A couple of things about memory

First:

Children's Memory May Be More Reliable Than Adults' In Court Cases

Researchers Valerie Reyna, human development professor, and Chuck Brainerd, human development and law school professor--both from Cornell University--argue that like the two-headed Roman god Janus, memory is of two minds--that is, memories are captured and recorded separately and differently in two distinct parts of the mind.

They say children depend more heavily on a part of the mind that records, "what actually happened," while adults depend more on another part of the mind that records, "the meaning of what happened." As a result, they say, adults are more susceptible to false memories, which can be extremely problematic in court cases.

The implications of these results for legal testimony is not what I find especially interesting here. In fact, there are reasons why the testimony of children has sometimes been found to be less reliable than that of adults. Namely, in some cases, the techniques used to interview the children (before trial) have been improperly coercive or suggestive of particular interpretations.

What does seem interesting is the hypothesis that in adults memories of the same event tend to be stored in two distinct forms: literal details of "what happened", and interpretive judgments about the "meaning" of an event. But that in children it is primarily the actual details that are stored.

Reyna and Brainerd's Fuzzy Trace Theory hypothesizes that people store two types of experience records or memories: verbatim traces and gist traces.

Verbatim traces are memories of what actually happened. Gist traces are based on a person's understanding of what happened, or what the event meant to him or her. Gist traces stimulate false memories because they store impressions of what an event meant, which can be inconsistent with what actually happened.

The researchers have experimental evidence to support their conclusions. Some of this is noted in earlier accounts, such as this:

Children Less Prone To False Memories, Implications For Eyewitness Testimony, Study Shows

In a study published in the May issue of Psychological Science, Brainerd and Reyna presented a list of words for groups of first, fifth and ninth graders. Many of the words from this "study list" were related to each other (by belonging to certain categories such as animals, furniture, men's names) while others were unrelated "filler" words.

After a short break, the students were presented with a new "test list" composed of study list words, new words belonging to the aforementioned categories (animals, furniture, etc.), and distracter words that were new and entirely unrelated to the categories or the study list. Their task was to identify whether they had previously heard a word or not.

As predicted, if the test list provided a new word with a closely related meaning (a "semantic relation") to a word from the study list, older children were more likely to assert that they had heard it before. Simply put, the older children had more false memories in this case than younger children.

One can speculate about what's going on here. As people mature through childhood, they are constantly learning about the interrelationship of isolated details and events. (For instance, "Dad acts more scary after he's been drinking beer.") In addition, the accumulation of details makes more literal forms of memory cumbersome (and liable to confusion), so people learn to make abstractions and interpretations that summarize details and make storage easier by associating similar details in more general categories. However, this kind of fuzzy storage (or "fuzzy traces" as Brainerd and Reyna call it) can misrepresent the facts. (For instance, "Dad was drunk when he hit me" – which might not actually be true.)

Second, and not directly related to this, there are two quite indepentdent studies that show something about the relationship between memory and experience of stress.

The first item concerns observation of squirrels:

Correct Levels Of Stress Hormones Boost Learning, Squirrel Study Suggests

Tests on the influence that a stress-related hormone has on learning in ground squirrels could have an impact on understanding how it influences human learning, according to a University of Chicago researcher.

Jill Mateo, Assistant Professor in Comparative Human Development, has found that when they perform normal survival tasks, ground squirrels learn more quickly if they have a modest amount of cortisol, a hormone produced in response to stress, than those with either high or low levels of cortisol.

In humans, cortisol production is also related to stress and is known to have an impact on learning, but that impact is not well understood, Mateo said.

This should sound familiar to anyone who's been through even a few moderately difficult college courses. Namely, if the work in a particular course isn't difficult enough to cause at least a little stress, retention of the details may not be very complete. Without some stress, the material just doesn't seem "important" enough, even if it's new to the student, to compel the student's attention to the details and the complexity. But of course, if the material is difficult enough to cause excessive stress, anxiety can get in the way of successfully organizing the material in the student's mind.

The second study looked at the actual neurobiology of learning under conditions of acute stress:

Short-term Stress Can Affect Learning And Memory

Short-term stress lasting as little as a few hours can impair brain-cell communication in areas associated with learning and memory, University of California, Irvine researchers have found.

It has been known that severe stress lasting weeks or months can impair cell communication in the brain's learning and memory region, but this study provides the first evidence that short-term stress has the same effect.

As it turns out, another stress-related hormone besides cortisol is involved, corticotropin releasing hormone (CRH), and the latter is more significant under conditions of acute stress:

In their study, Baram and her UC Irvine colleagues identified a novel process by which stress caused these effects. They found that rather than involving the widely known stress hormone cortisol, which circulates throughout the body, acute stress activated selective molecules called corticotropin releasing hormones, which disrupted the process by which the brain collects and stores memories.

Learning and memory take place at synapses, which are junctions through which brain cells communicate. These synapses reside on specialized branchlike protrusions on neurons called dendritic spines.

In rat and mouse studies, Baram's group saw that the release of CRH in the hippocampus, the brain's primary learning and memory center, led to the rapid disintegration of these dendritic spines, which in turn limited the ability of synapses to collect and store memories.

The researchers discovered that blocking the CRH molecules' interaction with their receptor molecules eliminated stress damage to dendritic spines in the hippocampal cells involved with learning and memory.

The role of cortisol, in learning under conditions of moderate stress, remains somewhat less clear. In addition to the squirrel study, anecdotal experience with so-called "flashbulb memories" supports the idea that some degree of stress can assist the formation of memories. The Wikipedia article states, without references, "Some biologists believe that the hormone cortisol, which is released in response to stressful incidents, cooperate with epinephrine (adrenaline) to cause the formation of flashbulb memories by the brain, functioning to help remembering things to avoid in the future." The squirrel study suggests cortisol actually has some role in memory formation, rather than being just a coincidental byproduct of stress. (See also the article on Emotion and memory.

Tags: memory, stress, cortisol, corticotropin-releasing hormone

Memory and long-term potentiation

To begin with, we have an in-depth series of four recent articles by Terry McDermott of the Los Angeles Times on Gary Lynch and his work on the neurobiology of memory. In spite of some minor criticisms, it's as heroic a piece of exposition as one will find in the mass media. You can learn a lot about the current "story" of how memory works by reading these articles.

You can learn a lot more, besides – namely, how science really works. This particular story is quite amazing actually. Lynch's career has had more ups and downs than a roller coaster. I wouldn't be surprised to see the story made into a Hollywood drama before too long.

Except for one thing: it's not over yet. The tight connection between long-term potentiation has been for the last 30 years or so just a hypothesis. Only about a year ago was the paper published that seems to be accepted as the long-awaited verification of the hypothesis. And it's merely one of the ironies of this Byzantine story that this confirmatory paper came out of a laboratory at the other end of the country from Lynch's. Unfortunately, McDermott does not even mention this part of the story. To make up for that, you will find at the end of this note some references to work that has appeared in the past year on long-term potentiation. One of them is about Gary Lynch and his associates and the goal they managed to (finally) achieve.

The most exciting thing about it all is that the accomplishment is just the beginning, not the end of the story. What seems to have been achieved is a technique for actually visualizing memory traces. This should make it possible eventually to map out how memories are laid down in the brain, in a manner that could become as routine as the technique of staining cells for microscopy was 100 years ago.

Unfortunately, I can't quickly summarize the story that McDermott tells in his series of articles. Even though it could take you several hours to read through the whole thing, it's worth it. I wouldn't be surprised to see this turned into a book (and then into the movie) – but you'll learn the story much sooner if you just read the articles.


The text following each item is quoted material, except for editorial comments, which are in color.

One man's epic quest for understanding

Lynch is a neuroscientist at UC Irvine, where he has spent 37 years trying to uncover the biochemical mechanisms of memory.

He has, for almost the length of his career, been trying to answer essentially a single pair of questions: What happens in the brain when a human being encounters a new experience so that he or she can recall it at will tonight, tomorrow, in 2025? And what goes wrong when we can't remember?

Trials, and a series of errors, in the brain lab

Yanagihara one day, finally, working with the brains of young rats, got his experiment to work right, and found the result he was expecting to find. "If we get it tomorrow in middle-aged rats, it's great," he said.

"If you see a garbage can flying out of the lab onto the hedge, you'll know we didn't," Kramar said.

The next day, the trash cans remained inside, but only because nobody had the energy to throw them out the window. The experiment had failed again.

Unfortunately, one can't rely on the technical accuracy of everything written in this series. An example in this part is the confusion of nitric oxide with nitrous oxide. The former is the molecule of greater interest in biology, while the latter is "laughing gas". At least the error is acknowledged in a note within the article. But it makes one wonder just how many other details not so readily checked can be relied upon. Like, for instance, the reference to antibodies as just "chemicals" – well, yes, but...

Breakthroughs, and new crises, in the lab

After weeks of repeated failures on almost every other front, Lynch was ecstatic. "You mean this crap actually works?" he said. "You don't expect to see a result this black-and-white. You expect ambiguity. Aging does not occur uniformly even across a single neuron. It's an instant default explanation for memory loss. It's getting to the point where we might have to start believing we were right."

Another bit of sloppy writing in this installment of the series. In one place it says, correctly, that a neuron has just one axon. Then in the same paragraph it talks about the "axons" of one neuron.

Success and rejection

It seemed fitting, somehow. There he sat at the end of the great, long chase, often sick as a dog, the entry locked, the clamorous tribes of the neurosciences a low hum in the distance; no phone, no e-mail, not even a name on the door to betray his presence. The only way you would know he was there at all was the blue Corvette out front. And, of course, the science, which, no matter the circumstance, difficulty or hour, had poured out for 30 years like water from the well. And poured still.

Memory: a glossary of terms

You might want to keep this glossary open in a separate window if you need help with some of the terminology.

Further references

And now we have some pointers to the additional details, as promised early on.

• Researchers Provide First Evidence For Learning Mechanism In Brain – July 2006 press release describing the paper published in Science that asserts strong evidence for the connection between long-term potentiation and memory.
  
• Learning Induces Long-Term Potentiation in the Hippocampus – The actual research paper published in Science. (Subscription required to read the whole thing.)
  
• ZAP and ZIP, a Story to Forget – "Perspectives" article that accompanies the research report. Online version has links to much background material. (Sub. rqd.)
  
• First Images Of Brain Changes Associated With Memory Revealed – May 2007 press release about the culmination (for now) of Lynch's own LTP research.
  
• Drug Triggers Body's Mechanism To Reverse Aging Effect On Memory Process – July 2006 press release on publication of an article about Lynch's research on ampakines.
  
• Proteins Anchor Memories In Our Brain – November 2006 press release about publication of related work on LTP.
  
• Researchers Investigate The Molecular Basis Of Memory In Living Mice – January 2007 press release about additional LTP research.
  

Tags: neuroscience, neurobiology, memory, long-term potentiation, Gary Lynch, ampakines

Stuff I forgot to mention about memory

And speaking of memory here and here, there's recent research I forgot to mention. Oh, the irony. (Damn! I sure hope someone comes up with a memory pill, and fast.)

First up is a gene named Kibra. It's expressed in the hippocampus, and has been found to be associated with memory performance.

Research Team Identifies Human 'Memory Gene'

The impact of the study is that it gives the research community a new and important handhold into truly understanding the process of memory. The ramifications of this report are ultimately developing new and effective medicines that can combat memory loss, and that might also help improve memory in people with memory disorders like Alzheimer's disease.

The team has already begun working on new drugs to restore memory function in age-related memory loss and diseases that have a memory loss component.

What this press release doesn't make clear is that discovering exactly what the protein corresponding to this gene does in neurons of the hippocampus will help us understand memory better. And that in turn may help find ways to augment memory even in people who don't have memory disorders.

In the meantime, while we're awaiting such a breakthrough, research has found ways to make the best use of the memory we have. First:

Asleep at the Memory Wheel

Going a night without sleep may cause your hippocampus to go on strike. A new study has caught this crucial memory-encoding brain region slacking off in college students the day after they've pulled an all-nighter. The study is one of the first to investigate how sleep deprivation interferes with memory mechanisms in the human brain.

Unfortunately, you need a subscription to Science in order to see the full article, but the key point is this:

To find out which part of the brain was responsible for this forgetfulness, the researchers repeated the experiment with a different group of undergrads, but this time used functional magnetic resonance imaging (fMRI) to monitor brain activity while the students viewed a set of emotionally neutral photographs. The fMRI scans revealed lower activity in the hippocampus of sleep-deprived students than in well-rested students. This suggests that just as sleep is important for consolidating new memories after they're learned, as other studies have shown, it's equally important for preparing the brain to learn new things the following day.

This work was done by Matthew Walker and his colleagues at Harvard. Here are several reports of releated work they've done previously.

• Study shows how sleep improves memory
  
• Sleep helps memory
  
• Sleep to Remember
  
• New stage of memory found: Combines with sleep to make better memories
  
• Sleep Replenishes the Memory Bank
  
• Stages of memory described in new study
  
• "Power Nap" Prevents Burnout; Morning Sleep Perfects a Skill
  

One last item – if you want a good memory, lay off the weed:

Marijuana wreaks havoc on brain's memory cells

Smoking marijuana often causes temporary problems with memory and learning. Now researchers think they know why.

The active ingredient in the drug, tetrahydrocannabinoid (THC), disrupts the way nerves fire in the brain’s memory centre, a new study shows.

David Robbe at Rutgers University in New Jersey, US, and colleagues gave rats an injected dose of THC, proportional to the amount inhaled by a person smoking an average-sized marijuana joint.

The team monitored the drug’s effect using wire probes placed in a memory centre in the animals’ brains – the hippocampus. The probes monitored the nerve impulses as they fired.

Normally, cells in hippocampus fire in sync, creating a current with a total voltage of around 1 millivolt. But THC reduced the synchrony of the firing. The drug did not change the total number of firings produced, just their tendency to occur at the same time – and this reduced the combined output voltage of the nerve signals by about 50%.

Abnormal firing occurs because THC binds to a receptor on the surface of the nerve cell, and so indirectly blocks the flow of current, Robbe believes.

See also: Marijuana's High Times Not Memorable with Neurons Out of Sync

Tags: neuroscience, memory, sleep, cannabis

Improving your memory

Who wouldn't like to have a better memory? Probably nobody, except maybe Solomon Shereshevskii or the fictional Ireneo Funes.

Neuroscientists are coming up with various small steps towards better memory:

Scientists Use Gene Therapy To Improve Memory And Learning In Animals

Stanford University neuroscientists have designed a gene that enhances memory and learning ability in animals under stress. Writing in the Nov. 8 issue of the Journal of Neuroscience, the Stanford team says that the experimental technique might one day lead to new forms of gene therapy that can reduce the severe neurological side effects of steroids, which are prescribed to millions of patients with arthritis, asthma and other illnesses.

"Steroids can mess up the part of the brain involved in judgment and cognition," said neuroendocrinologist Robert Sapolsky, co-author of the study. "In extreme cases it's called steroid dementia. Ideally, if you could deliver this gene safely, it would protect the person from some of these cognitive side effects, while allowing the steroid to do whatever helpful thing it should be doing elsewhere in the body."

Unfortunately, gene therapy is (at least presently) rather a drastic technique:

[T]his type of gene therapy will not be medically available until scientists figure out a way to safely deliver the chimeric gene to humans, Sapolsky said. He also noted that the treatment should be used to prevent severe neurological side effects caused by medication and should not be given to those who simply want to enhance their short-term memory and learning skills. "You can't drill into people's heads and inject a virus just because somebody has a big exam coming up, " he said.

OK, so maybe it's back to the drawing boards. Here's something that, at least, doesn't require a Black & Decker:

A Stimulating Slumber

Each night as you sleep, your brain buzzes with electrical activity. Neuroscientists suspect that that this activity helps solidify memories formed during the day. Now, they've bolstered their case: for the first time, researchers have shown that electrically stimulating the brain during sleep can enhance memory performance the following day.

We might call that a "proof of concept". Looks a little better, but still sort of cumbersome. However, if you're taken with the idea there are more references on the study here and here.

OK, guys, let's try once more. Can't we do just a little better? Maybe:

Hopkins researchers discover how brain protein might control memory

Researchers at Johns Hopkins have figured out how one particular protein contributes to long-term memory and helps the brain remember things longer than an hour or two. The findings are reported in two papers in the Nov. 9 issue of Neuron.

The protein, called Arc, has been implicated in memory-linked behaviors ranging from song learning in birds to rodents being aware of 3-D space.

It turns out that this Arc protein works indirectly by controlling a couple of other proteins:

To figure out what Arc was doing, the Hopkins team looked for what other proteins Arc "plays" with. Using Arc protein as bait, they went on a molecular fishing expedition in a pond filled with other proteins normally found in the brain and hooked two known to be involved in transporting materials into and out of cells.

"Moving things in and out of cells is critical for normal brain cell function. We were extremely excited that Arc might somehow be involved in this transport because it links transport to memory formation," says Worley. "This brings us one step closer to understanding how the brain saves memories."

According to Worley, memories form when nerve cells connect and "talk" to other nerve cells. It's thought that the stronger these connections are, the stronger the memory.

Bueno. Muy bueno. Unfortunately, proteins don't work very well when delivered in pill form. (The stomach tends to digest them.) But perhaps we're getting closer to something that will help you pass that bar exam.

Tags: neuroscience, memory

Thanks for the memories

We're all pretty concerned about how well our memory works, right? There's now evidence that the quantity of the neurotransmitter acetylcholine present in the brains of test animals (rats, of course) is directly related to the level of detail of new memories:

Researchers discover mechanism that determines when detailed memories are retained

The levels of a chemical released by the brain determine how detailed a memory will later be, according to researchers at UC Irvine.

The neurotransmitter acetylcholine, a brain chemical already established as being crucial for learning and memory, appears to be the key to adding details to a memory. In a study with rats, Norman Weinberger, research professor of neurobiology and behavior, and colleagues determined that a higher level of acetylcholine during a learning task correlated with more details of the experience being remembered. The results are the first to tie levels of acetylcholine to memory specificity and could have implications in the study and treatment of memory-related disorders.

The findings appear in the November issue of the journal Neurobiology of Learning and Memory.

"This is the first time that direct stimulation of a brain region has controlled the amount of detail in a memory," said Weinberger, a fellow at UCI's Center for the Neurobiology of Learning and Memory. "While it is likely that the brain uses a number of mechanisms to store specific details, our work shows that the level of acetylcholine appears to be a key part of that process."

It isn't news that acetylcholine is related to memory. As a neurotransmitter, acetylcholine is released by presynaptic projections of a neuron's axon in order to cause activation (or inhibition) of a postsynaptic neuron. Normally, the neurotransmitter must be quickly degraded in the synapse so as not to continue to affect the postsynaptic neuron.

However, it was discovered that inhibiting the degradation of acetylcholine (which is normally done by the enzyme acetylcholinesterase) can improve memory performance of persons with early stage Alzheimer's disease. And so acetylcholinesterase inhibitors have turned out to be popular drugs for treating early Alzheimer's.

A little is known about how acetylcholine is involved in memory. It is generally assumed now that memory is a phenomenon of "synaptic plasticity" that occurs when the strengths of connections between neurons increase in proportion to how often signals pass between the neurons – so-called "long-term potentiation". (There has been experimental confirmation of this hypothesis only recently – see this report.) Acetylcholine has been shown to enhance the amplitude of synaptic potentials following long-term potentiation in many regions of the brain.

What the recent research reported here seems to show is that deliberately increasing the quantity of acetylcholine in the brain leads to the formation of more detailed memories.

Sounds like a useful thing to be able to do whenever one needs to cram for a crucial exam...

Tags: neurobiology, acetylcholine, memory, long-term potentiation

Memory traces

The question of where and how memories are stored in the brain is one of the most intriguing in neuroscience. Answers to this question are just starting to emerge, as reported here.

That research dealt with short-term memory in honeybees. It showed that the memory trace involves synchronized neural activity lasting for several minutes. The activity was in clusters of neurons known as glomeruli in the bee's antenna lobe. This area is considered to be the equivalent of the olfactory bulb in vertebrates (which handles the sense of smell).

Now there are additional results involving longer-term memory in fruit flies.

Memory follows dynamic pattern involving many cells in brain

Memory formation follows a dynamic pattern, allowing for retrieval from different areas of the brain, depending on when an organism needs to remember, said a researcher at Baylor College of Medicine.

That is what Dr. Ron L. Davis, professor of molecular and cellular biology at BCM, theorizes, based on his most recent report on the topic that finds a memory trace in Drosophila or fruit flies is formed in a pair of neurons called the dorsal pair medial neurons, but only 30 minutes after the fact and only through the mediation of a gene called, ironically, amnesiac.

The really interesting thing is that the trace of a specific memory does not appear to remain in one place, but instead seems to move around:

The finding belies the commonly held precept that a memory is formed in the same way that data are stored in a computer - always in the same place.

"It's not as if we are forming memories that are then being written to a "hard disk" area of the brain, and it's there and recalled from the same location at any time after learning," said Davis. "We now think that different areas of the brain have dominion over small intervals of time after training. One area might have dominion and then another."

Tags: memory trace, neuroscience

First evidence of a living memory trace

What is a memory, physically, as it resides in the brain? Looks like there's progress finding out:

Scientists find first evidence of a living memory trace

An international team of scientists for the first time has detected a memory trace in a living animal after it has encountered a single, new stimulus. The research, done with honeybees sensing new odors, allows neuroscientists to peer within the living brain and explore short-term memory as never before, according to scientist Roberto Fernández Galán, a leading author on the report who is currently a postdoctoral research associate at Carnegie Mellon University.

What was it, exactly, that they found?

"Our findings show that an odor produces a memory trace of synchronized neural activity that lasts several minutes after a bee initially senses it," said Galán. "This is the first time anyone has revealed a short-term, stimulus-specific neural pulse within the living brain that occurs after exposure to a previously unknown stimulus."

Tags: memory, memory trace