RNA Moves a Memory From One Snail to Another

Injecting molecules from a sea slug that received tail shocks into one that didn’t made the recipient animal behave more cautiously. 

By Ashley Yeager | May 14, 2018

WIKIMEDIA, GENNY ANDERSONResearchers have transferred a memory from one snail to another via RNA, they report today (May 14) in eNeuro. If confirmed in other species, the finding may lead to a shift in scientists’ thinking about how memories are made—rather than cemented in nerve-cell connections, they may be spurred on by RNA-induced epigenetic changes.

“The study suggests that RNA populations are the missing link in the search for memory,” Bridget Queenan, a neuroscientist at the University of California, Santa Barbara, who was not involved in the study, writes in an email to The Scientist. “If circulating neural RNAs can transfer behavioral states and tendencies, orchestrating both the transient feeling and the more permanent memory, it suggests that human memory—just like mood—will only be explained by exploring the interplay between bodies and brains.”

For decades, researchers have tried to pinpoint how, when, and where memories form. In the 1940s, Canadian psychologist Donald Hebb proposed memories are made in the connections between neurons, called synapses, and stored as those connections grow stronger and more abundant. Experiments in the 1960s, however, suggested RNA could play a role in making memories, though the work was largely written off as irreproducible.

See “Learning Enhances Synapses Between ‘Memory Cells’ in Mice

Study coauthor David Glanzman of the University of California, Los Angeles, has been working on the cell biology of learning and memory for nearly 40 years, and says for the majority of that time he believed memory was stored at synapses. Several years ago, though, he and his colleagues began replicating memory-erasing research done in rodents in California sea hares (Aplysia californica), a type of marine snail also called a sea slug. The team found that the snail synapses built to “store” a memory weren’t necessarily the synapses that were removed from the neural circuits in the memory-erasing experiments.

“It was completely arbitrary which synaptic connections got erased,” Glanzman says. “That suggested maybe the memory wasn’t stored at the synapse but somewhere else.”

Glanzman turned his attention to RNA because of those earlier hints it was related to memory, and also because of recent experiments suggesting long-term memory was stored in the cell bodies of neurons, not synapses. He picked Aplysia because it has been a longtime model organism for memory studies. Like all mollusks, these snails have groups of neurons called ganglia, rather than brains. Their nervous systems comprise about 20,000 neurons, and the cells are some of the biggest and easily identifiable among nerve cells in all animals. In the snail’s gut, for example, are specific sensory and motor neurons that control the withdrawal of a fleshy, spout-like organ on the snail’s back called a siphon and the contraction of a caterpillar-looking gill, which the animal uses to breathe.

When touched lightly on the siphon, the neurons fire, retract the tissue, and contract the gill within the body cavity for a few seconds to protect it against attack. Sticking electrodes in the snail’s tail and shocking it makes this defensive response last longer, tens of seconds, and sometimes up to almost a minute. By repeatedly shocking the snail’s tail, the animal learns to stay in that defensive position when touched on the siphon, even weeks after the shocks end.

This idea is probably going to strike most of my colleagues as extremely improbable.

—David Glanzman,
UCLA

 

In his team’s latest experiments, Glanzman and his colleagues zapped snails’ tails, then pulled the abdominal neurons from the shocked snails, extracted their RNA, dissolved the RNA into deionized water, and injected the solution into the necks of snails that had never been shocked. (For a control, the team also took RNA from non-shocked snails and injected into naive snails.) When tapped on the siphon 24 hours later, snails that got RNA from shocked snails withdrew their siphon and gill for significantly longer (almost 40 seconds) than did snails that got RNA from non-shocked animals (less than 10 seconds).

DNA methylation appeared to be essential for the transfer of the memory among snails. When Glanzman and his colleagues blocked DNA methylation in snails getting RNA from shocked ones, the injected snails withdrew their siphons for only a few seconds when tapped on the siphon.

Glanzman wanted to know if the RNA from shocked snails actually affected the neuronal connections of the snails receiving the injections any differently than RNA from nonshocked snails. So, in a third test, he and his team removed sensory neurons from nonshocked snails, cultured the cells in a dish, and then exposed the cells to RNA from shocked snails. Zapping the culture with a bit of current excited the sensory neurons much more than neurons treated with RNA from nonshocked snails. RNA from shocked snails also enhanced a subset of synapses between sensory and motor neurons in vitro, suggesting it was indeed the RNA that transported the memory, Glanzman explains.

The idea “seems quite radical as we don't have a specific mechanism for how it works in a non-synaptic manner,” Bong-Kiun Kaang, a neuroscientist at Seoul National University who was not involved in the study, writes in an email to The Scientist. Kaang notes there are “many critical questions that need to be addressed to further validate the author’s argument,” such as what kinds of noncoding RNAs are specifically involved, how are the RNAs transferred among neurons, and how much do RNAs at the synapse play a role? The experiments should also be replicated in organisms other than snails, he says.

Glanzman says that in his next experiments he will attempt to identify the RNAs involved, and he has an idea for the mechanism, too. The memory is not stored in the RNA itself, he speculates—instead, noncoding RNA produces epigenetic changes in the nucleus of neurons, thereby storing the memory.

“This idea is probably going to strike most of my colleagues as extremely improbable,” Glanzman says. “But if we’re right, we’re just at the beginning of understanding how memory works.”

A. Bédécarrats et al., “RNA from trained Aplysia can induce an epigenetic engram for long-term sensitization in untrained Aplysia,” eNeuro, doi.org/10.1523/ENEURO.0038-18.2018, 2018.

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Avatar of: PastToTheFuture

PastToTheFuture

Posts: 118

May 15, 2018

This has been suspected for a while. There is a weird reason why I have kept aware of research on this topic. The only explanation I could find for something I observed was if a meme could be encapslated that way. Not just that the idea was contageous - a meme, but that it could be transferred "in a physical form" rather than communicated. This isn't what I research, so I can say what I want (I always do anyway), but it is reasonable to believe that there are actually ideas floating around in the form of molecules.... but they are only contageous if there are "receptors" in the brain for them. Now this is a valid model in psychology of ideas communicated by normal communication vectors, but dang if I haven't seen ideas show up multiple places at the same time where there were no obvious communication vectors. It's like they are floating out there, constantly being picked up, but only noticed by someone able to process them. Think about this a little. This is obviously absurd, I know, but it also makes some sense and makes me wonder if they could be artifacts. I've observed them multiple times, but why study what you aren't going to make sense of?

Avatar of: Hugh-F-61

Hugh-F-61

Posts: 77

May 15, 2018

Is this transfer of memory or state? A tail-shock should make a slug alert to danger and increase the protection response, turning on genes for, say, adrenalin and cortisol production (or the slug equivalents). Transfer of RNA might well stimulate the same genes in the recipient, but it need not be a memory, rather it could be a response state. Being epigenetic it could be long lasting, but it still would not be a memory of  "something stung my tail". Similarly, squashing greenfly (aphids) causes other greenfly to run away, poking an ant will make its mates attack you, just as the attached one will try to do, but it is as a response to pheremones, they don't  "remember" being personally attacked. They just become more anxious.

Avatar of: James V. Kohl

James V. Kohl

Posts: 532

May 15, 2018

RNA editing: when what you se(quence) isn’t what you get

Quantized energy-dependent / food energy-dependent RNA interference has been linked from RNA editing to biophysically constrained viral latency at every level of examination. Mutations link the virus-driven degradation of messenger RNA to all pathology.

George Church tried to place what is known about natural occurring RNA-mediated genetic engineering into the context of this patent application

 He now appears to now be moving away from the horrors of CRISPR-Cas9 to food energy-dependent precision medicine in the context of the cell biology game "Cytosis" for ages 10+ . See: Cytosis - The Science Behind the Game


"This is the four page booklet that explains the science in Cytosis. It was written and edited collaboratively by 20 PhD's and Doctors "through the world.  
 

Avatar of: Jon S

Jon S

Posts: 1

May 16, 2018

In 1965, while a student at U of M, Ann Arbor, I had a part time job as an assistant in the lab of James V McConnell, a psych professor who did RNA memory transfer with flatworms (The Worm Runner's Digest). When I was there, we were doing it with rats. Train a rat to do a maze or something like that, take the brain of that rat, extract the RNA and inject it on to the cortex of recipient rats. He demonstrated the abilities of those rats to do better at the challenge than control rats. No one believed the studies were legit and funding dried up. Thus was born The Journal of Irreproducible Results. It's mind boggling to see RNA memory engram work more than a half century later. Makes me smile for old Ann Arbor memories

Avatar of: 20120607124528200

20120607124528200

Posts: 14

May 16, 2018

When we making cDNA libraries from brain mRNA we found that a major fraction of RNA was polyA- but couldn't figure out a function. It would  be interesting to know if it functions in memory. 

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