Updated* Manipulating memory in mice: What to do when a sexy neuroscience story is (almost) too complex to explain

Addendum: When I first started reading these stories on mouse memory manipulation, I thought it was my fault that I couldn’t comprehend the versions written for a general readership. Maybe I was too tired, or too distracted. But a closer look revealed the problem to be missing steps – details the researchers may have left out of their press briefing but were nevertheless crucial for the story to make sense.

In my search for comprehensible stories, I was late to come across Researchers erase fearful memories in mice by Emily Underwood, for Science. This story includes an explanation that makes sense. And it really isn’t all that long. She adds explanatory material from an outside source and keeps the story compact by leaving out some of the boiler plate that took up space in many other versions.

Science writers sometimes ask readers to trudge through rough intellectual terrain. One way you risk losing those readers is to lead them to think some skipped step should be obvious, when in fact you don’t even understand it, or you can’t figure out how to explain it in a reasonable number of words.

In many stories, it’s impossible to explain everything, but a good science writer can signal to readers when they should be able to connect the dots themselves, and when those dots don’t actually connect as you’ve presented them.

A good case in point surfaced this week in the coverage of an intriguing Nature paper on the manipulation of memory and emotion. The claim was, roughly, that researchers were able to manipulate the brains of mice in order to make them feel fear associated with a certain region of an enclosure and then switch the association to a pleasant one. Needless to say, the very thought of such profound mind meddling led to international headlines.

The scientists emphasized that their experiment offered insight into the way circumstances sometimes shift the emotional content of an association. “Recalling the week you just spent at the beach probably makes you feel happy, while reflecting on being bullied provokes more negative feelings,” was the example given in the MIT news release and reporters tweaked the example in different ways, most of them using romantic situations/breakups.

There was the obligatory conjecture about using the knowledge to help people – especially those with PSTD or other disorders.

But what was astonishing and even a little chilling was the experiment itself, and what it said about the possibility of turning good memories bad, or fearful ones pleasant. The procedure relied on a technique that actually allows researchers to tag neurons activated in the formation of a memory and then reactivate those neurons and switch on the memory later. How is such a feat done? It’s not magic, but it was hard to explain in a simple newspaper story. The trick here was to either go into the details or at least warn readers of the gaps.

At the Wall Street Journal, Gautam Naik covered the news in Scientists Experiment With Reworking Memory in Mice

They began by giving one set of mice fearful memories (via a small electric shock to the foot) and by giving other mice pleasurable memories (by allowing them to interact with female mice). By firing the laser into the mouse brain, the scientists could identify the specific brain cells that were activated when each of the two memories were formed.

How does the laser tell them which cells were activated when a memory was formed? This is not obvious.

At The New York Times Pam Belluck covered the story in Scientists Switch Bad Memories for Good Ones in Mice:.

The M.I.T. scientists labeled neurons in the brains of mice with a light-sensitive protein and used pulses of light to switch the cells on and off, a technique called optogenetics. Then they identified patterns of neurons activated when mice created a negative memory or a positive one.

A negative memory formed when mice received a mild electric shock to their feet; a positive one was formed when the mice, all male, were allowed to spend time with female mice.

Later, mice that had been shocked were put in the company of females, a positive experience, while scientists used the light to activate the memory of the shock.

Again, how do they identify the neurons associated with the bad memory and set things up so light activates them? Sounds like magic.

At The Washington Post, Rachel Feltman covered the news in Scientists switch ‘good’ and ‘bad’ memories in mice

They exposed half of them to a positive stimuli (interaction with a female mouse) and half to a negative one (small electric shocks). This activated both the neurons that form the structure of a memory, which are found in the hippocampus, and the neurons that determine the emotional value of a memory, in the amygdala.

Then the mice were placed in a box with two sides that the mice could move freely between. When the mice moved to one particular end of the box, a light would shine down on them —activating the neurons that had been active during their conditioning.…”

That last sentence sounds like it should make sense, but why would the light only activate the neurons that had been active during the conditioning?

Here’s USA Today’s story, Light can switch bad memories to good, by Traci Watson:

They quickly learned that whenever they ventured into a certain section of the chamber — call it the target zone — they were flooded with the unpleasant memory of the electrical shock. Naturally enough, the mice avoided that part of the chamber.

The bad vibes were actually the handiwork of the scientists, who deliberately turned on the painful memory with the help of a laser that activated the brain cells where the painful memory was stored.

And at Reuters, Tricking memory in lab animals stokes hope for PTSD By Sharon Begley

The mice had been engineered so specific brain neurons could be activated with light, a technique called optogenetics. Using lasers, the scientists reactivated the where, what and when of the memories, which are encoded in the hippocampus.

While the shock memory was active and labile, the mice got to play with females. While the memory of socializing was active, they got a shock.

The Independent: Eternal sunshine of the spotless mouse: Scientists successfully erase bad memories in rodents By Charlie Cooper

Scientists were able to identify the neurons that were active during the forming of each memory. These same neurons were then manipulated using light – a technique called optogenetics which uses light-sensitive organisms to control cell activity.

Science News covered the story with Laser light rewrites memories in mice. It’s behind a paywall.

There are a couple of approaches to telling this story without making readers hit their heads against the wall or give up, thinking they’re too stupid to get it. One way is just to explain the whole complicated procedure. That was the approach Ben Thomas took in Discovery’s D-Brief, with  Researchers “Copy and Paste” Fear From One Memory to Another

MIT neuroscientist Roger Redondo and his team started by gathering a sample group of genetically engineered mice. The mice’s brains were engineered so that, if an antibiotic known as doxycycline was removed from their diet, certain neurons in their brains would express a protein called channelrhodopsin-2 (ChR2) which triggers neural activity in response to blue light.

This system enabled the team to use doxycycline as a sort of “record/pause” button for neural activity in the animals’ brains. The investigators could remove the antibiotic from the mice’s diet, give the animals certain kinds of conditioning, then start giving them doxycycline again; thus creating light-sensitive groups of neurons that had activated during specific time periods and tasks….

But Redondo and his team decided to take things one step further, and find out if it was possible to link the mice’s “where” memories — those of certain locations in their enclosure — with new and different “what” memories — those of fear and reward. So the team used light to reactivate the mice’s fear memories again, this time while those mice interacted with a female.

Sure enough, after nine days of this conditioning, the mice had become terrified of their romantic playmates — meaning the researchers had essentially “copied and pasted” the fear from the shock memory onto the mice’s memories of the female. 

Aha. So that’s how they did it! It’s not obvious at all – certainly not something readers should be able to infer.

One variation on the story that worked well was the Boston Globe’s New studies erase traumatic memories in mice by Carolyn Y Johnson. This story combined the Nature paper with another memory-related paper from PLOS ONE. The story is written in a way that readers understand it’s a brief overview with steps missing.

The MIT research used a technique called optogenetics, which involves laser light and genetic tweaking, to activate specific memories when mice were having scary or pleasurable experiences . They found that they could alter the valence of the memory — making something the mice previously feared into something they sought out, or the reverse.

Thanks for reading. Remember to always check your blind spots, be mindful of assumptions and take nothing on faith without reason. – Faye Flam fayeflamwriter.com

 

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5 comments / Join the Discussion

    Excellent piece! Optogenetics is one of the hardest techniques to explain well for lay audiences, I find. But what surprises me most is that the most detailed and best explanatory writing example is not all that terribly long here. Certainly could have been done within the lengths of most of the articles cited. And should have.

    It seems both the USA Today and Science News headlines suffered from a lack of understanding that the light is simply a laboratory tool and not the key point here.

    Kendall, that seems like a pretty large overstatement — “a lack of understanding.” Read our story (and USAT’s) and see if you think that’s the case.

    I’m sure our hed is not perfect. But as you know, there are restrictions on headline style and substance, and sometimes the word that one writer/editor might choose to emphasize does not end up at the front of someone else’s headline.

    As to Faye’s main point: Laura Sanders did a skilled job at explaining the technique, giving a nod of the head to readers when she was skimming over steps: “A molecular trick marked neurons that stored the memory of each experience so that the cells, and the memory they evoke, could be later activated with laser light piped through tiny optical fibers embedded in the mice’s brains…”

    (Full disclosure: I’m the news editor at Science News, but her story was assigned, written and edited while I was on vacation, so I can take absolutely no credit for it.)

    Oh, you are so right about this! How many times, even in well-respected and highly credible papers and magazines, have I come across articles that baffle readability. Is something missing here? I often ask. Science writing is enormously difficult, particularly on a deadline. But media outlets should allow editors plenty of time to query with the kind of questions posed in this blog and send stories back to the journalists for clarification.

    Good commentary. I will repeat Rensberger’s First Rule of Science Writing: Never try to explain something you don’t understand.

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