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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

Your Love Is My Drug: The Science Of A Broken Heart

By Nicole Tay
CommonHealth Intern

Valentine’s Day is around the corner, and we know what that means. Cheesy cards and too many heart-shaped candies, yes, but also, possibly: a break-up.

According to an analysis of Facebook statuses, the weeks following Valentine’s Day mark one of the most common periods during the year to end a relationship. A break-up at any time is miserable, but perhaps a scan of the latest brain science might ease some of the agony. Maybe.

(Nicholas Raymond/Flickr)

(Nicholas Raymond/Flickr)

NPR recently dove into this topic and took a look at some psychological therapies for a broken heart. But what about chemical, neurobiological and other treatments? Could a brain implant for a broken heart be in your future?

First, a quick look at the chemicals driving our desire to please, the yearning for our lovers and our addiction to love. Many of us are familiar with the euphoria associated with the feeling of being in love, and its counterpart, the crushing grief that can accompany a break-up.

When a romantic relationship ends, our brains work tirelessly to rewire our associations with our ex-lovers.

Similar to cases of drug addiction, falling out of love can entail a physically and emotionally painful withdrawal period. In fact, addiction to another person appears to parallel drug addiction anatomically and functionally. In a 2012 review of social attachment, love and addiction, researchers identified numerous areas of neurological overlap between love and other drugs.

Not only do we utilize some of the same neurotransmitters and regions of our brain to maintain these addictions, the researchers found, but we also exhibit the same “reward-seeking” behavior when we do not get our fix. The difference (or at least one difference) is that love is a socially acceptable form of drug addiction. Continue reading

Diaper Power: Expanding Gel Could Help Scientists See Brain Workings

If this were a glam-genius movie along the lines of “The Imitation Game,” we’d see an exhausted, stymied scientist changing the over-wet diaper of his cranky baby, then suddenly straightening up and gasping in the throes of a revelation: “What if — what if — we don’t try to improve the microscope? What if we just make the thing we’re trying to see bigger? We could expand it just like the gel in this huge wet diaper!”

Sadly, it didn’t happen that way. So the moral of this story is not that scientists should change more diapers. But a report just out in the journal Science does point the way to a promising new scientific tool that could prove helpful in the monumental efforts under way to map the brain. And yes, it involves diapers — or rather, the polymer gel that makes disposable diapers expand so rapidly when wet.

Turns out, with some chemical tweaking, that gel can be used to expand brain tissue without distorting its structure, so it may allow scientists to map the nano-scale 3-D connections between neurons — even potentially to get a full picture of how information flows in small animal brains or parts of the human organ.

I spoke with neuro-engineer Ed Boyden of MIT’s Media Lab and McGovern Institute for Brain Research, senior author on the new study in Science, co-authored with MIT grad students Fei Chen and Paul Tillberg. Our conversation, lightly edited:

How would you sum up what you report in this “Science” paper?

Over the last several hundred years, microscopists have been imaging life. The way they do it is they use a glass lens to magnify the light coming out of the biological sample. This has been very, very powerful, and untold numbers of insights have emerged from it, but there’s a problem: How can you image a large, 3-D object with nano-scale precision? Light cannot go down to very, very fine precision because light is sort of finite in size, you could say. It has a wavelength that’s really large compared to single molecules.

What we’ve found is that, in contrast to lens-based magnification, you can physically magnify an object and make it bigger. So that was the first key finding: We can physically magnify an object.
The second key finding is that we have engineered a chemical system that lets you do this very, very precisely and with good resolution.

And a third take-home message from the paper is that we have now shown that the chemical process we developed is very isotropic — that is, it’s very smooth and even, and doesn’t introduce distortion, all the way down to the nanoscale.

Why does being able to analyze brain tissue at this nanoscale resolution matter?

If you want to understand the brain, well, brain circuits are quite large. The individual cells in the brain could be millimeters or centimeters in size in terms of their length. But the actual things that organize the brain — the connections called synapses — are nanoscale. So if you want to understand how a brain circuit funnels information or processes information, you need to be able to map a large, 3-D object with nanoscale precision, and that’s something our technology is enabling.

What could be done with it?

In neuroscience, we’re excited by the possibility that you could try to map an entire small brain, in organisms like flies or worms. We think it’s possible you could expand the entire nervous system or the entire brain and then see the whole thing.

That would be very exciting because you could try to follow the pathways that lead in from the sensory organs — like the eyes — all the way to the motor outputs — to the muscles, and look at all the stuff in between: What makes decisions? What makes memories? And then map that.

One could imagine that at some time in the future you could try to load up these molecular maps of a neural circuit into a computer and then try to simulate a brain in a computer.

What about human brains? Continue reading

Brain Science, Dangerous? Not So Fast, Says Poverty Expert

Back in June, we wrote about a novel program in Boston that seeks to lift women and their families from poverty, in part by using the latest research in neuroscience. Specifically, the program (developed by the nonprofit Crittenton Women’s Union) takes into account recent studies that reveal how trauma, and poverty, can rewire the brain and potentially undermine executive function.

In an Op-Talk piece in this week’s New York Times headlined “Can Brain Science Be Dangerous?” writer Anna North cites our story, and then goes on to question whether this type of approach might be problematic. In the article, North refers to sociologist Susan Sered:

Dr. Sered…says that applying neuroscience to problems like poverty can sometimes lead to trouble: “Studies showing that trauma and poverty change people’s brains can too easily be read as scientific proof that poor people (albeit through no fault of their own) have inferior brains or that women who have been raped are now brain-damaged.”

She worries that neuroscience could be used to discount people’s experiences: “In settings where medical experts have a monopoly on determining and corroborating claims of abuse, what would happen when a brain scan doesn’t show the expected markers of trauma? Does that make the sufferer into a liar?”

We asked Elisabeth Babock, president and chief executive officer of Crittenten Women’s Union, to respond to the Times piece. Here, lightly edited, is what she wrote:

Moving out of poverty in the U.S. today is an extremely complicated and challenging process. It involves trying to maintain a roof over your head when the minimum wage doesn’t cover the minimum rent; and trying to get a better paying job when almost all those jobs require education beyond high-school and the costs of that education, in both money and time, are well beyond the means of most low-wage workers. It involves trying to care for a family while filling in the gaps in what the minimum wage will buy with increasingly-frayed public supports. It involves a lot of juggling.

We at Crittenton Women’s Union (CWU) understand this process all too well because we work with hundreds of people trying to navigate their way out of poverty every day: homeless families living in our transitional housing and domestic violence shelters, and people who are living on the edge of homelessness, struggling to make ends meet. What we at CWU see is that the stress of this everyday struggle creates an additional set of monumental challenges for those we serve.

Our families often describe themselves as feeling “swamped” by their problems to the point that they can only think about how to deal with the crisis of the moment. And in those moments, they may not have the mental bandwidth to strategize about how to change their current circumstances or help them get ahead.

One of the most valuable things brain science research does for this struggle is that it validates what our families share about the way being in poverty affects them. Instead of saying that stress leaves people “irrevocably debilitated”, or worse still, that people should somehow rise above this crippling stress to “just move on” the science actually suggests something much more important. It calls upon all of us to understand that poverty, trauma, and discrimination are experiences whose cumulative effects impact our health, decision-making, and well-being in tangible and predictable ways, and because of this, we as a society can and must do our best to remediate it. Continue reading

Can Brain Science Help Lift People Out Of Poverty?

Five years ago Lauretta Brennan was a single mom on welfare with a pack-a-day smoking habit, stuck in a “bad” relationship and living in the South Boston projects where she grew up.

Now, she’s still living in the projects with her young son, but the bad boyfriend is gone and Brennan’s got a job as an administrative assistant after receiving a business management degree. And she quit smoking.

Her childhood in the projects was marked by alcoholism and violence all around, Brennan said; “having no adult role model was the norm, being with a man who’s ignorant, that was the norm.”

Lauretta Brennan graduated from Bunker Hill Community College with an Associates Degree in Business Management in June 2013 (Courtesy)

Lauretta Brennan graduated from Bunker Hill Community College with an Associates Degree in Business Management in June 2013 (Courtesy)

But now, thanks to a novel program that uses the latest neuroscience research to help women dig themselves out of poverty, Brennan says: “I don’t want to live off welfare. I want to make money and be around people who work and go to school. In five years, the program got me to think more like an executive — I have goals, I’m an organizer managing my family well. I’m not scared anymore.”

This shift in thinking — from chaotic, stressed-out, oppressed and overwhelmed to purposeful and goal-oriented — may not sound like brain science. But it fits into an emerging body of research that suggests that the stress of living in poverty can profoundly change the brain: it can undermine development and erode important mental processes including executive function, working memory, impulse-control and other cognitive skills.

To fix that damage, the new thinking goes, people must engage in activities and practices that strengthen this diminished functionality and, exploiting the brain’s ability to change (plasticity in neuroscience lingo) re-train themselves to think more critically and strategically.

“Poverty whacks executive function and executive function is precisely what’s needed to move people out of poverty,” says Elisabeth Babcock, chief executive of the nonprofit Crittenton Women’s Union, a Boston-based group that draws on the latest brain research to help families achieve economic success. “What the new brain science says is that the stresses created by living in poverty often work against us, make it harder for our brains to find the best solutions to our problems. This is a part of the reason why poverty is so ‘sticky.'”

In a recent paper, “Using Brain Science To Design New Pathways Out Of Poverty,” Babcock makes the case that living in an impoverished environment “has the capacity to negatively impact the decision-making processes involved in problem-solving, goal-setting and goal attainment.” In other words, this type of stress can “hijack” the brain.

As other researchers, including Jack Shonkoff, director of the Center on the Developing Child at Harvard, have noted, this chronic vise of pressure — to pay the bills, function at work, raise the kids, and simply survive in an atmosphere rife with social bias and harsh living conditions — “places extraordinary demands on cognitive bandwidth.” Babcock writes:

“The prefrontal cortex of the brain — the area of the brain that is associated with any of the analytic processes necessary to solve problems, set goals and optimally execute chosen strategies — works in tandem with the limbic system, which processes and triggers emotional reactions to environmental stimuli…When the limbic brain is overactive and sending out too many powerful signals of desire, stress, or fear, the prefrontal brain can get swamped and the wave of emotion can drown out clear focus and judgement…”

How does this play out in real life? Chuck Carter, senior VP of research at Crittenton Women’s Union, explains:

“One of the things the brain science brings is something of an ‘aha’ in terms of why things are sometimes harder than we expect them to be. When you’re looking at a family that is struggling and making decisions that you don’t really understand, having that research helps you reassess…it adds another perspective. A lot of nonprofit organizations look at the social determinants [of poverty] but not a lot look at the science that says, ‘What else is at play?’

“I think that, on the ground, it gives us creative ways to think about the work and how we might approach it…Often families are in a lot of crises…and they feel they need to do things ‘right now.’ So, for instance, we’ve got a family, and they’re in a hallway and they’ll have to talk to the case manager ‘right now.’ And we ask whether it’s a true emergency, and if not, can we talk about this the next morning, and not in the hallway. It’s a problem with executive function and poor impulse control, but we can help them slow down and figure out the right time to figure this out and what information do they need. It’s about not responding so impulsively in other parts of their lives. So, in thinking about what to do with money, it can be a question of, ‘Do I buy cigarettes now or save the money for some new furniture when I move?'”

So how do you begin to fix all of this?

I asked Babcock a bit about the science behind her organization’s Mobility Mentoring program, in which low-income — mostly single — mothers apply to get training, professional mentoring, financial and other support for three to five years, in hopes of attaining economic independence.

Here, edited, is our discussion:

RZ: What does the research say about how poverty changes the brain? And how does a “hijacked” brain function compared to a brain not experiencing intense, chronic stress?

EB: Poverty hits what scientists call our executive functioning skills: our ability to problem-solve, set priorities and goals, juggle and multi-task, focus and stick to things. And it does this in at least two very important ways. First, the stress of dealing with new problems every day and never having enough to make ends meet overwhelms our heads and swamps us. It overloads the circuits in our brains and compromises our decision-making in the moment. Continue reading

Rock Stars Of Brain Science Gather In Boston

I was remarking upon the truly astonishing line-up of luminaries attending Rep. Patrick Kennedy’s major brain conference in Boston today, launching an initiative that aims to take on the brain as a challenge on the scale of JFK’s drive to the moon 50 years ago. “It’s just about everybody who’s anybody,” I said — all the names of federal agency leaders and high-profile scientists I’d covered for years on the brain beat.

Yes, said another attendee, “They really brought out all the rock stars of brain science.”

So call me a groupie, but I homed in on one particular scientist whose work I’ve admired from afar but never covered: Dr. Karl Deisseroth of Stanford. He leads work that many see as a real game-changer in brain science. His best summary: “The combination of genetics and optics to achieve gain and loss of function.” My best simplification: You engineer neurons so that, say, green light turns them on, red light turns them off. Green light: scared. Red light: Not scared any more.

Here’s Karl kindly obliging with sound bites:

Many at the Kennedy conference have noted that the brain is frustratingly hard to experiment on, stuck as it is inside the skull and endlessly complex. Optogenetics lets us effectively turn things in the brain off and on, to test hypotheses, figure out how ciruits work and someday, perhaps, fix them.

Actually, for mice, that day may already have come. Karl Deisseroth’s team showed this spring that they could apparently reduce the anxiety of a mouse by manipulating it optogenetically. The Times reported earlier this month:

Treating anxiety no longer requires years of pills or psychotherapy. At least, not for a certain set of bioengineered mice. In a study recently published in the journal Nature, a team of neuroscientists turned these high-strung prey into bold explorers with the flip of a switch. The group, led by Dr. Karl Deisseroth, a psychiatrist and researcher at Stanford, employed an emerging technology called optogenetics to control electrical activity in a few carefully selected neurons.
First they engineered these neurons to be sensitive to light. Then, using implanted optical fibers, they flashed blue light on a specific neural pathway in the amygdala, a brain region involved in processing emotions.
And the mice, which had been keeping to the sides of their enclosure, scampered freely across an open space.

Obligatory disclaimer: Manipulating circuits in mice is a long way from doing it in humans. Continue reading