Memories selectively, safely erased in mice

[Dante]

New and old memories have been selectively and safely removed from mice by scientists.

 

"While memories are great teachers and obviously crucial for survival and adaptation, selectively removing incapacitating memories, such as traumatic war memories or an unwanted fear, could help many people live better lives," says Dr. Joe Z. Tsien, brain scientist and co-director of the Brain & Behavior Discovery Institute at the Medical College of Georgia School of Medicine.

 

"Our work reveals a molecular mechanism of how that can be done quickly and without doing damage to brain cells," says the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology.

 

Dr. Tsien's research team, in collaboration with scientists at East China Normal University in Shanghai, were able to eliminate new and old memories alike by over-expressing a protein critical to brain cell communication just as the memory was recalled, according to research featured on the cover of the Oct. 23 issue of Neuron.

 

Dr. Tsien had already created a mouse that couldn't form memories by eliminating the NMDA receptor, which receives messages from other neurons. He then garnered international acclaim by making "Doogie," a smart mouse in which a subunit of the NMDA receptor is over-expressed. Younger brains have higher amounts of this NR2B subunit which leaves communication channels between brain cells open longer. That is why young people can learn faster than older adults.

 

This time he was examining downstream cascades of the NMDA receptor to learn more about memory formation. An abundant protein found only in the brain, called αCaMKII, was a logical place to look because it's a major signaling molecule for the NMDA receptor. He found that when he over-expressed αCaMKII while a memory was being recalled, that single memory was eliminated.

 

Receptors such as the NMDA receptor are like front doors to cells, providing an opening for signaling molecules such as calcium. Synapses are the point of communication between two cells, and NMDA receptors are on the receiving end of the message. Like people, neurons change with the signals they receive. "Learning changes the way cells connect to each other," says Dr. Tsien. To form a memory, the NMDA receptor is activated, which results in the insertion of AMPA receptors into those synapses and subsequent strengthening of the synaptic connections among hundreds of thousands of neurons. Scientists believe that αCaMKII plays an important role in the insertion of AMPA receptors into synapses during learning and subsequent strengthening of connections between neurons to create a memory.

 

Memory has four distinct stages: learning, consolidation, storage and recall. It has been difficult to dissect the molecular mechanisms of these stages because researchers lacked techniques to manipulate proteins quickly. For example, when researchers disable a gene suspected to play a role in the memory process, the deletion typically occurred throughout the entire period so it was impossible to tell which parts of processes were impaired. Previous technology would take several days to switch off a protein, which is the product of a gene.

 

So Dr. Tsien's team developed a powerful chemical-genetic method that allows him to use a pharmacologic inhibitor to instantly turn αCaMKII off and on in a mouse that he genetically engineered to over express this signaling molecule. That enabled him to study exactly what happened if he threw off the natural balance during the retrieval stage.

 

Much as a war veteran remembers a fateful patrol when he was fired upon, mice can establish a very long-lasting emotional memory about a place if, for example, they receive a mild shock to the paws while there. The researchers showed if they over-expressed αCaMKII, this powerful memory was rapidly erased as the animals tried to retrieve them while other memories remained intact.

 

A similar approach was taken with object recognition memory, giving mice a couple of toys to play with then erasing their memory of one of them. "You will feel like every time, it's a new toy," says Dr. Tsien.

 

While the ability to rapidly erase a selective memory is exciting, he cautions that its translation to humans would be difficult at this stage. "We are barely at the foot of a huge mountain," says Dr. Tsien. A possible strategy for humans would be a drug that mimics the αCaMKII over expression that researchers accomplished through genetic manipulation. Or, further downstream substrates that αCaMKII acts upon could become possible drug targets.

 

eurekalert.org

[Raining_again]

this sounds like something taken from Eternal Sunshine of the Spotless Mind! Great film.

[Paj!]

You just know this will lead to the mice overthrowing us in the end.

[Dante]

this sounds like something taken from Eternal Sunshine of the Spotless Mind! Great film.

 

Yeah also sounds like something taken from Joss Whedon's Dollhouse.

[Hellfire]

Also sounds like a Boston Legal episode. Memories are a part of us, our worst moments are as defining if not more than the best ones, opening the doors to just erase them at a whim is basically saying it's OK to put the brakes on the moral, ethical and personal evolution of an individual.

[The fish]

That could be very, very effective as a treatment for post-traumatic stress, especially soldiers...

[Supergrunch]

Erm, this is slightly insane. I wouldn't get your hopes up until after peer review. (also, their methods aren't really explained - how do they know the mouse is attempting to recall a particular memory?)

 

Anyway yeah, need a paper.

[ReZourceman]

My mouse doesn't even have a memory card slot, let alone internal memory.

[rokhed00]

Don't see how they can prove anything conclusive from this, not like a mouse can tell them what it has forgotten.

[Tellyn]

Reminded me of this fellow.

 

 

If they can somehow do the same thing for humans, it'll be great for people with post-traumatic stress, as Fish said.

[ShadowV7]

That's exactly what I got reminded of.

 

Also, as folk have said, how can you tell what a mouse thinks/has forgotten. Maybe the mouse loved cheese but after the experiment, didn't know what it was. I think that's as far as they can go

[Mundi]

MY NAME IS NOT QUAIIIIIIIIIIIIIIIIIIIIID!

[Jonnas]

(also, their methods aren't really explained - how do they know the mouse is attempting to recall a particular memory?)

 

My mouse doesn't even have a memory card slot, let alone internal memory.

 

Don't see how they can prove anything conclusive from this, not like a mouse can tell them what it has forgotten.

 

Also, as folk have said, how can you tell what a mouse thinks/has forgotten. Maybe the mouse loved cheese but after the experiment, didn't know what it was. I think that's as far as they can go

 

In case you don't know, mice can memorize labyrinths. You put a piece of cheese in the end of the labyrinth, and he takes a while to find his way. You do it again, and he already knows the way, breezing his way through.

 

If they aim to take away a specific memory, they can take the labyrinth experiment away. Like do a few labyrinths, observe if they can do them again, take a few memories, and check which labyrinths he doesn't remember.

 

Anyway, taking away memories may be good for people with serious post-traumatic stress, but I can't see any other beneficial uses.

[Rummy]

I'm getting scared of how we're advancing technologically on the biological side of things. I saw something on the Wright Stuff papers section about now being able to screen for serious disorders in the womb, possibly within the time frame for abortions, and I mean...I dunno, what's happening to natural selection or whatever? We've survived this long without it, do we really need it? Fish does raise a good point though, I would kind of agree with that, maybe.

 

(Didn't really read all of the first post admittedly, I kinda side with Supergrunch and take some of these things with a pinch of salt)

[Supergrunch]

In case you don't know, mice can memorize labyrinths. You put a piece of cheese in the end of the labyrinth, and he takes a while to find his way. You do it again, and he already knows the way, breezing his way through.

 

If they aim to take away a specific memory, they can take the labyrinth experiment away. Like do a few labyrinths, observe if they can do them again, take a few memories, and check which labyrinths he doesn't remember

I'm well aware of that, but we aren't told that what's done, and I would like to know the experimental method, which would be in a paper. Also, the claim is that over-expression of the αCaMKII protein when a particular memory is being recalled causes that memory to be forgotten. That's all very well, but I can't see a way of devising an experiment that ensures the mouse is recalling a particular memory, especially as spatial memory (or any memory for that matter) is hardly atomic, apart from maybe at the synaptic level. Surely a maze experiment would contain far too many memory variables for you to really see what was going on, even if you're able to turn off expression of the protein at will.

[Shino]

I'd like to forget all about Zelda OOT or Mario Galaxy. Except how much I like them.

[Jonnas]

I'm well aware of that, but we aren't told that what's done, and I would like to know the experimental method, which would be in a paper. Also, the claim is that over-expression of the αCaMKII protein when a particular memory is being recalled causes that memory to be forgotten. That's all very well, but I can't see a way of devising an experiment that ensures the mouse is recalling a particular memory, especially as spatial memory (or any memory for that matter) is hardly atomic, apart from maybe at the synaptic level. Surely a maze experiment would contain far too many memory variables for you to really see what was going on, even if you're able to turn off expression of the protein at will.

 

Honestly, I don't know much about the chemical, or how memory works.

I was just pointing out that there are ways to see if a mouse forgot something.

 

I'd like to forget all about Zelda OOT or Mario Galaxy. Except how much I like them.

 

That...would be so sweet.

[Dannyboy-the-Dane]

I'd like to forget all about Zelda OOT or Mario Galaxy. Except how much I like them.

 

That's ... that's GENIUS! We all know the first time is the best - sexual jokes aside. We could relive all out favourite moments of life for the first time again!

 

About the news, I also have some doubts about how this actually works. Also, the ethical issues have to be taken into account. Already I can hear the conspiracy theorists' minds working at full steam.

[Zero]

That's ... that's GENIUS! We all know the first time is the best - sexual jokes aside. We could relive all out favourite moments of life for the first time again!

 

About the news, I also have some doubts about how this actually works. Also, the ethical issues have to be taken into account. Already I can hear the conspiracy theorists' minds working at full steam.

 

King V will be along any moment :p

 

This could be a very good thing or a very bad thing. I believe all memories are important to defining yourself as a person but, I would agree there are a few exceptions to this.