Researchers Say They Can Lift Depression In Mice By Activating Happy Memories



You know when you’re feeling really down, or worse, in the throes of depression, and there’s always that chirpy person who earnestly says: “Just try to focus on happy thoughts; think positive!” Well, it turns out, that unshakeable optimist may have a point.

MIT scientists report that they are able to “cure” the symptoms of depression — in mice — by artificially activating happy memories that were formed before the depression took hold.

The findings, published in the journal Nature, hint at a future in which depression might be treated by manipulating brain cells where memories are stored.

MIT graduate student Steve Ramirez, the lead author on the paper, explains that while the work is tantalizing, it’s a long way from any real-world application in people:

“We’re doing basic science that aims to figure out how the brain works and how it can produce memory,” Ramirez said in an email. “The more we know about how the brain works, the better equipped we are to figure out what happens when brain pieces break down to give rise to broken thoughts. In my opinion, we’re a technological revolution away from being able to do this in humans; everything that exists currently is too invasive and not targeted enough. That said, the underlying proof-of-principles are there, as we can do these kinds of manipulations in animals. The question is how we can do this in humans in an ethically responsible and clinically-relevant manner.”

Still, he says, researchers did not expect such clear results:

“The finding that stimulating positive memories over and over actually forces the brain to make new brain cells was surprising,” he wrote. “We did not expect to have such a clean result demonstrating that artificially activated positive memories correlates with an increase in the number of new brain cells that are made.” Continue reading

Amnesia Undone: MIT Study In Mice Restores Lost Memories

mouse neurons1

3-D reconstruction of mouse neurons (Zeiss Microscopy/Flickr Creative Commons)

How’s this for a grabber?

“Memories that have been ‘lost’ as a result of amnesia can be recalled by activating brain cells with light. In a paper published today in the journal Science, researchers at MIT reveal that they were able to reactivate memories that could not otherwise be retrieved, using a technology known as optogenetics.”

Yes! Does this mean we can reclaim our long-forgotten halcyon childhood days with a bit of a laser boost to the right neurons? Um, no, not today. But it’s still fascinating. That MIT press release quoted above goes on to explain that the study explores the difference between how a memory is stored — in a group of brain cells called an engram — and how it is retrieved. It quotes Nobel Laureate Susumu Tonegawa, who leads the group that did the work, on the evolving concept of what a memory is, in our brains:

“We are proposing a new concept, in which there is an engram cell ensemble pathway, or circuit, for each memory,” he says. “This circuit encompasses multiple brain areas and the engram cell ensembles in these areas are connected specifically for a particular memory.”

WBUR’s Rachel Paiste spoke with Dheeraj Roy, a grad student in Tonegawa’s MIT lab who worked on the research. Their conversation, lightly edited:

RP: So what did you find?

DR: We wanted to look at mouse models of amnesia, for the simple reason that there’s very little done today in the field. So we attempted to look at individual memory traces, which we refer to as engram cells, which are sparse populations in several brain regions — the one we worked with is the hippocampus, which is widely known to be involved in memory. And we looked at: Do these memory traces, which we see in normal mice, do they still persist in amnesic mouse models? And if so, is there any way that we can restore or bring back these memories?

And this is actually stemming from a debate in the field: Neuroscientists weren’t sure, when a mouse or a rat or a human can’t remember a memory, is it because the memories are no longer stored or is it because for some reason they can no longer be accessed? So our study really started with that goal: Can we try to tease apart storage problems, where the memory is gone, or retrieval problems, where the memory is there but just needs to be retrieved somehow?

So our findings, I think for the first time, tell us that in certain models of amnesia, memories do persist and, very importantly, at levels similar to what we see in control mice. And that’s actually what was most exciting for us: not just that memories persist — that’s been known for a while — but the fact that we can bring back memories to equivalent levels as control animals is very unexpected.

So the first thing I thought of here, knowing more about pop culture than brain science, is “Eternal Sunshine of the Spotless Mind.” As far as retrieval of memories, is this something that could somehow become used for humans? Continue reading

In Memory: A Fat Kid’s Love For Mr. Spock

By Steven Schlozman, M.D.

I remember the exact moment I realized that I could be Mr. Spock.

I was 9 years old, trapped in the “Husky” jeans section of the local Macy’s department store. Looking around at the selection of very big pants, I understood viscerally what I had known intellectually for years.

“Husky” meant “fat.” It meant that I was fat.

Not super fat, but fat enough to be in the Husky section.

I was awkward, developing in that tortured way that evolution see’s fit to make us endure. Staring at the mirror while my Mom gathered trousers for me try on, I was pissed off that because of this shopping trip, I was missing the rerun of “Star Trek” that aired on weekday afternoons.

(Daniel Arrhakis/Flickr)

(Daniel Arrhakis/Flickr)

“What would Spock think about the ‘Husky’ designation?” That’s what I was pondering. I was wondering how the master of logic would justify and make sense of the clearly derogatory way I was feeling about myself.

“Fascinating,” I imagined him saying, and he would raise that patented eyebrow.

Then I looked in the mirror, furrowed my brow, took note of the barely present peach fuzz growing under my nose, and with all the power of a Vulcan mind meld, I imagined that my right eyebrow was being pulled by a thread towards the stars. That one eyebrow was to boldly go where no eyebrow of mine had ever gone before.

And I did it. I raised that eyebrow.

“Fascinating,” I muttered. And then I did it again, and again. It was like a teeny Bar Mitzvah moment. “Today, I am a Vulcan.”

Spock meant that much to me. Spock could be friends with a tough guy like Kirk. Spock was unfazed by McCoy’s insults. Spock tolerated with admirable self-control the romantic advances of Nurse Chapel. Spock would, I was certain, be emotionally impervious to the Husky section of Macy’s.

“Fascinating,” I said, and again I raised my right eye brow.

I share the world’s sadness for Leonard Nimoy’s passing. I am grateful that he stuck around so long after he began his “five year mission.” I feel like a kid every time I hear his voice in the Imax theater at Boston’s Museum of Science. Every time I hear his voice, I am wearing Husky jeans but feeling OK about it.

These days I’m still raising one eyebrow on an almost daily basis. I even had a patient’s parent give me Vulcan ears for Christmas a few years ago.

“They’re not because you’re emotionally cold,” she explained.

No, I thought, Spock wasn’t cold.

“They’re because you’re not freaked out by our child. They’re because you’re interested.” Continue reading

2014: CommonHealth Year Of The Brain, From Depression To Dyslexia


A map of nerve fibers in the human brain (. (Courtesy of Zeynep Saygin/Massachusetts Institute of Technology.)

A map of nerve fibers in the human brain (. (Courtesy of Zeynep Saygin/Massachusetts Institute of Technology.)

Happy almost 2015. Instead of doing our usual “Top 10 CommonHealth stories of the year” post, we’ve decided instead to look back at our tip-top, far-and-away #1 organ of the year for 2014.

Hint: It’s well above the waist. The brain is, to quote Pink Floyd: “All that you touch/All that you see/All that you taste/All you feel./All that you love/All that you hate/All you distrust/All you save.”

Etcetera. The brain is also the focus of some of the most fascinating research in modern-day science.

Our 2014 series, “Brain Matters: Reporting from the Front Lines of Neuroscience,” tried to capture a partial snapshot of this pivotal moment in brain science, a time of new tools and insights so promising that scientists themselves are saying this is the most exciting time ever to work on the brain.

The series included the set of gorgeous images below, compiled by former intern Suzanne E. Jacobs, and a collection of short video interviews with young neuroscientists, produced by WBUR’s Jesse Costa: 11 Young Neuroscientists Share Their Cutting Edge Research.

The individual “Brain Matters” pieces, in reverse chronological order:

Wishing you a wonderful new year. Special thanks to WBUR’s Iris Adler, who supervised the “Brain Matters” series. And now, for your visual pleasure, the wondrous view inside your head: Continue reading

Facing The Inevitable: From Lost Keys To Dementia

I recently turned 50 and, on cue, my AARP card came in the mail and my doctor told me to schedule my first colonoscopy.

Also on cue, I’ve noticed what seems to be my own increased mental scattered-ness — misplaced keys, sluggish name recall. As a catastrophizer, I immediately link this apparent (but my doctor assures me normal) ever-so-slight decrease in cognitive sharpness to full blown Alzheimer’s and the start of a bleak, diminished future.

I am slightly comforted by two factors. First, I’m hardly alone. As Michael Kinsley eloquently reports in his recent New Yorker piece, “Have You Lost Your Mind?” we baby boomers are the first generation to have witnessed our parents cognitive decline and know in terrifying detail what’s in store for us; but at least we’re all on this sinking ship together. Second, there’s a lot of genetics behind Alzheimer’s and cognitive decline, and in that department, I’m not in bad shape. My parents kvetch, but they’re both nearly 80 and my mother, in particular, lives an incredibly active life on her own in Brooklyn: she recently learned chess, ushers off-Broadway with friends most weekends and walks and does yoga everyday.



Also, researchers are busily trying to tackle this problem on numerous fronts. On Sunday, for example, Harvard scientists reported what felt like a breakthrough: a new protein that in mice seems to have a rejuvenating effect on brains and muscles.

And a fairly technical study just out in Biological Psychiatry also hints at the possibility of future fixes: using something called “imaging genetics” researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health are trying to identify “key molecular switches that control age-related memory impairment” and are specifically looking at a protein known to play a role in human memory, called “KIBRA and the gene responsible for its production.” Continue reading

Hope For The Older Mind — Maybe Not Clueless, Just ‘Fuller’

Mr. Mo-Fo/flickr

Mr. Mo-Fo/flickr

Last week I inadvertently dropped my keys into the garbage at Starbucks.

Of course, I didn’t realize it at the time, and it took about 45 minutes of retracing — back to the baristas, who said no, they’d found no keys, back to Trader Joe’s, again no trace of lost keys, and back, once more, to Starbucks, where I sheepishly asked the pierced and rather dismissive coffee girl if I could rifle through the garbage. After going through several bags, I reached into the last one and there, covered in wet grinds and God knows what else, were my car keys.

At first, the incident made my heart heavy, and led me to this story line: I’m so very middle-aged and edging into cognitive decline, joining the ranks of my senior relatives who do clueless things like drop half-eaten apples into the mail box, forget their kids’ birthdays, tell that story about the guy with the pig farm in Montana again and again and again. But in a slight glimmer of positivity, I thought, some part of my brain remembered that I’d thrown a few things in the garbage, and another part urged me to forge ahead, into the dank underbelly of the Starbucks trash bags, until I emerged triumphant. In other words, in a tiny, distant quadrant of my brain there was cognitive crispness, or at least a murky memory that contained the location of my keys.

And lo, in The New York Times this morning, Benedict Carey bolsters my positivity with a story headlined: The Older Mind May Just Be A Fuller Mind. OK, it’s a study with no actual subjects and it’s highly preliminary, but I’ll take it:

“…the new report will very likely add to a growing skepticism about how steep age-related decline really is,” he writes.

And here’s a little background:

Scientists who study thinking and memory often make a broad distinction between “fluid” and “crystallized” intelligence. The former includes short-term memory, like holding a phone number in mind, analytical reasoning, and the ability to tune out distractions, like ambient conversation. The latter is accumulated knowledge, vocabulary and expertise. Continue reading

‘Total Recall’ For Mice: Scientists Implant False Memories

Arnold Schwarzenegger in "Total Recall" trailer (YouTube)

Arnold Schwarzenegger in “Total Recall” trailer (YouTube)

In “Total Recall,” Arnold Schwarzenegger’s best film ever (in my humble opinion), he plays a construction worker who seeks a “memory implant” from a company that provides them to customers who want a false memory of a wonderful vacation they can’t afford to take.

That’s just the beginning of the complex plot, based on the ingenious Philip K. Dick’s “We Can Remember It For You Wholesale,” but of course I thought of it immediately when I saw this major memory news out of MIT in the journal Science:

Researchers at the RIKEN-MIT Center for Neural Circuit Genetics and MIT’s Picower Institute for Learning and Memory have implanted false memories into mice, potentially illuminating the mechanisms underlying the human phenomenon of “recalling” experiences that never occurred.

In previous work, the researchers had detected a single memory in the brain, genetically tagged the brain cells housing that memory with a light-sensitive protein, and flickered pulses of light to “turn on” the memory at any given moment. The latest work, to be reported in the journal Science, tinkers with that memory to change its contents—in essence, creating a false memory.

Mars, here I come. (Schwarzenegger’s character signs up for a Mars vacation implant.) Actually — sigh — I doubt we’ll be implanting false memories of Mars trips any sooner than we get to Mars for real. But this new work does have more immediate implications for the study of how we make memories — including how we seem to remember things that never actually happened.

For more on how the experiment was conducted, read the Globe’s Carolyn Johnson’s excellent report here. I spoke with Susumu Tonegawa, the MIT brain scientist and Nobel laureate who led the work, about what it could mean. Our conversation, lightly edited:

So in what way is this experiment a “first”?

This is the first time a study allowed for the making of animal models of human false memory.

We knew that false memories existed in humans. So this is the first time that it’s been shown in animals that it’s possible to create a false memory and manipulate it?

That’s exactly right — and that’s important because in humans, all false memory has been studied by psychology. But the human studies had a lot of limitations in terms of understanding what’s going on in the brain. So an animal model is very important.

How would you describe the implications of these animal findings for humans?

First, in terms of practicality, I think we’ve shown how easily false memory can be formed. And also, in terms of underlying brain mechanisms, we have demonstrated that the mechanism for forming false memory is virtually identical to the mechanism underlying the formation of real memory. Continue reading

More Reason To Sleep On It: Sorting Out The Brain’s ‘Inbox’


Imagine you’re cleaning off your desk. You sort some papers into folders with the relevant labels. Others you red-tag as “urgent” or yellow-tag as “semi-urgent.” Quite a few go directly into the large circular file at your feet, also known as the trash basket.

Turns out, it seems that your brain does something very similar with your memories every night as you sleep.

The journal Nature Neuroscience has just published a special issue on memory, and among its authors is Dr. Robert Stickgold of Beth Israel Deaconess Medical Center and Harvard Medical School, a leading researcher on the role that sleep plays in consolidating memories.

In the past, my layperson’s take-home message from his complex research might have been, “Sleep helps strengthen memories. So if it’s the night before an exam and you have the option of cramming more or sleeping, better to sleep.”

But there’s ever so much more to know, and for researchers to find out — about sleep states beyond REM, about how our brains “tag” some memories for retention and dump others, about how sleep can improve performance overnight — even about why toddlers so desperately need naps.

Our conversation, lightly edited:

You’ve written a sweeping review of years of recent research on what sleep does to memories. How would you sum up for a lay audience what we now know?

I’d start by telling them a true story, which is that about 50 years ago, my father commented to me that when he was in law school studying for an exam, he would stay up late at night reading case after case, and go to sleep with a complete mishmash of cases in his mind. When he woke up the next morning, they had just all been filed away in the right spot. That was 50 years ago, and I can now say, ‘Yes, and now we have an idea how.’

It really does happen while you sleep, and although some of it can happen while you’re awake, especially if you’re consciously working at it, sleep seems to be a time that’s been set aside to make sure that filing gets done, even without your awareness or intent.

So sleep is a time of sorting and discarding memories?

Sleep is doing about five things. Continue reading

Your Brain On Butter: The Fats That May Hasten Mental Decline

Researchers link saturated fats found in butter and red meat to cognitive and memory decline in older women. (madlyinlovewithlife/flickr)

What’s good for the heart is good for the brain, the medical thinking goes.

Here’s the latest twist: What’s bad for the heart turns out to be bad for the brain. Put another way, some fats may make us stupider — or at least less cognitively on the ball.

Amid growing evidence that what we eat has a profound impact on brain function, researchers at Brigham and Women’s Hospital in Boston found that women who consumed the highest amounts of saturated fat — which can come from animal fats like red meat and butter — had worse overall cognitive function and memory over four years of testing compared to women who ate the lowest amounts of such fats. Moreover, women who consumed the most monounsaturated fats — think olive oil — scored better on the cognitive function tests over time.

(Trans-fats found in processed and baked goods — like those ginormous muffins they used to sell at the corner deli — are also considered “bad” but in this particular study, they weren’t associated with declines in cognitive ability.)

To be clear, this latest research doesn’t mean that if you start cooking with olive oil instead of butter you’ll suddenly be able to locate your car keys or remember your mother-in-law’s birthday.

But it does strongly suggest that the type of fat you eat matters, Continue reading

Harvard Memory Expert On Rick Perry’s ‘Oops’ Moment

You almost had to feel sorry for Rick Perry last night.

His breathtaking inability to remember the third federal agency he’d shut down as President (!!) was so utterly embarrassing — at that level, in that context, for that long — I wondered whether there must be some biological breakdown behind it.

So I emailed leading memory researcher Daniel L. Schacter, a professor of psychology at Harvard, and asked what he thought. Here’s his quick response:

The kind of memory problem suffered by Perry corresponds to what I called
“blocking” in my book on The Seven Sins of Memory (2001) – blocking is the third of the seven sins. Blocking refer to a temporary inability to retrieve information that is available in memory. Interestingly, blocking occurs most commonly for proper names, as was the case here. Blocking can be increased by stress and also by aging, although we can’t know for sure whether either one was a factor in this instance. Also, blocking tends to occur for information that is familiar, but has not been retrieved frequently or recently – again, I don’t know for sure whether that applies here.