Scientists discover how the brain encodes memories at a cellular level

December 23, 2009
A neuron. Credit: Sourav Banerjee

Scientists at UC Santa Barbara have made a major discovery in how the brain encodes memories. The finding, published in the December 24 issue of the journal Neuron, could eventually lead to the development of new drugs to aid memory.

The team of scientists is the first to uncover a central process in encoding memories that occurs at the level of the synapse, where connect with each other.

"When we learn new things, when we store memories, there are a number of things that have to happen," said senior author Kenneth S. Kosik, co-director and Harriman Chair in Neuroscience Research, at UCSB's Neuroscience Research Institute. Kosik is a leading researcher in the area of Alzheimer's disease.

"One of the most important processes is that the synapses -- which cement those memories into place -- have to be strengthened," said Kosik. "In strengthening a synapse you build a connection, and certain synapses are encoding a . Those synapses have to be strengthened so that memory is in place and stays there. Strengthening synapses is a very important part of learning. What we have found appears to be one part of how that happens."

Part of strengthening a synapse involves making new proteins. Those proteins build the synapse and make it stronger. Just like with exercise, when new proteins must build up muscle mass, synapses must also make more when recording memories. In this research, the regulation and control of that process was uncovered.

The production of new proteins can only occur when the that will make the required proteins is turned on. Until then, the RNA is "locked up" by a silencing molecule, which is a micro RNA. The RNA and micro RNA are part of a package that includes several other proteins.

"When something comes into your brain -- a thought, some sort of stimulus, you see something interesting, you hear some music -- synapses get activated," said Kosik. "What happens next is really interesting, but to follow the pathway our experiments moved to cultured neurons. When synapses got activated, one of the proteins wrapped around that silencing complex gets degraded."

When the signal comes in, the wrapping protein degrades or gets fragmented. Then the RNA is suddenly free to synthesize a new protein.

"One reason why this is interesting is that scientists have been perplexed for some time as to why, when synapses are strengthened, you need to have proteins degrade and also make new proteins," said Kosik. "You have the degradation of proteins going on side by side with the synthesis of new proteins. So we have now resolved this paradox. We show that protein degradation and synthesis go hand in hand. The degradation permits the synthesis to occur. That's the elegant scientific finding that comes out of this."

The scientists were able to see some of the specific proteins that are involved in synthesis. Two of these -- CaM Kinase and Lypla -- are identified in the paper.

One of the approaches used by the scientists in the experiment was to take live neuron cells from rats and look at them under a high-resolution microscope. The team was able to see the and the places where proteins are being made.

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not rated yet Dec 23, 2009
...the RNA is "locked up" by a silencing molecule, which is a micro RNA.

What I want to know is how come there is a molecule that switches off the RNA not the DNA? RNA lives for very short time before it is degraded itself. So if microRNA sits on the RNA, that blocking has to last for very short time. And therefore, I guess, this process has to repeat many times before any breaking up of microRNA occurs.

Repeat quickly many times when thought does not come in: (Build RNA, attach microRNA to RNA, degrade RNA).
If thought comes in: (detach microRNA).

Is that right?
5 / 5 (2) Dec 23, 2009
Partially, you are correct. RNA does degrade much faster than DNA. However, it is impossible for the neurons to apply DNA to this purpose. Primarily, you can't get from DNA to protein nearly fast enough for it to be applicable to this process. You would need transcription factors binding to DNA, helicase activity, RNApolymerase recruitment... and that's assuming the DNA isn't all buttoned up tight in some chromatin structure. No, while this process is indeed "wasteful" in terms of RNA loss, it's the only feasible process that can be activated fast enough to respond to synaptic activity.

One more thing: You'll only find DNA in the nucleus, which is quite far removed from the axon terminal where this activity is no doubt occurring. I could be wrong, as they didn't explicitly say where this translation is occurring, but it seems logical.
not rated yet Dec 23, 2009
Cognition enhancing drugs will be so huge. Since they will be a optional drug for most people and demand will likely be massive I'm guessing that they will fetch a high price(which should fuel R&D investment like a nuclear rocket).

I believe they will also be very important to economies of the future. Breakthroughs in cognition enhancement can turn never heard of countries into economic powerhouses. Even with a super memory you still need to will to learn but unfortunately many of the mature countries are full of lazy people(I live in U.S. and am not saying I'm perfect either). What happens when China and/or India starts handing out these future drugs like candy? Do the mature counties become obsolete? What I'm saying is once this gets started it will be unstoppable.

Happy Holidays!!!
not rated yet Dec 24, 2009
We get to witness the uncovering of the processes which underpin memory and learning in our lifetime. Maybe I have just stayed up too late, but this seems kind of momentous to me.
not rated yet Dec 24, 2009
Yeah, it sounds good, but does the headline hold water?
5 / 5 (1) Dec 24, 2009
Cells have mechanisms for manufacturing RNAs ahead of time and preserving them to release rapidly when they are needed. The protein / microRNA complex is probably another such mechanism, stabilizing the the RNA to keep it from being degraded.

So the process is probably more like:
Repeat when energy available and stored memory RNA supply is low: (Build RNA, attach microRNA to RNA, stabilize and store).
If thought comes in: destabilize and detach microRNA.
5 / 5 (1) Dec 24, 2009
Also, the degrade protein and detach microRNA release process is probably not an inefficiency. The microRNA may serve as a tag that says ‘Store Me’ upon production. Alternatively the two-step release process could enable extremely fast release from detaching microRNAs, and then replenishing the RNA/micronRNA pair from the stored protein complex.

Among its many purposes, sleep may well allow waking thought to be faster or more efficient by building up reserves of various 'thought chemicals' for rapid release. I'd guess more efficient due to not having observed either a species-to-species or a person-to-person correlation between average sleep time and speed of thought.
not rated yet Dec 24, 2009

Very nice explanation and interesting thoughts about the sleep. Thanks. I did not know much about microRNA. I will try to study that very important part of the cell function.
not rated yet Dec 25, 2009

This is an interesting question: if some of that process takes place still in the body of the neuron (and then the mRNA, miRNA, RISC complex is transported to the axon terminal), and if not, how can mRNA and miRNA float so far for the storage in the presynaptic part of the axon. I see in some other papers that the existence of ribosomes outside of the body of neuron is discussed.
not rated yet Dec 25, 2009
Better memory does not mean that a person smarter.
Just like a computer - full hdd means the computer slows down.
We should reduce the amount of our memory to free up the creative output of the brain ...maybe
not rated yet Dec 25, 2009
Upside may be eidetic memory on demand. Danger is education must quickly switch to *understanding* lest rote-learned data drowns comprehension. And, uh, how-do you un-learn old data as research etc progesses ??

Must wonder if misuse of memory enhancing drugs will create epidemic of PTSD-like symptoms, where a 'flash-bulb memory' is stamped on victim's psyche like ultimate, recurring bad-trip...

eg: Take a Memory Pill before an event so it stays sharp, and find yourself stuck with the minutiae, literally unable to get past it. And if anything went wrong ? Stuff of nightmare...

Dire possibilities cascade: Imagine a psycho dosing some-one before inflicting abuse, or terrorists dosing their hostages...
not rated yet Dec 25, 2009
Misuse of memory enhancing drugs? Alarmist enough? Of course there will be misuse, there's always misuse, that doesn't mean we should stop doing research and exploring our universe. If we don't do it someone else will, and god forbid it's a rogue nation plotting to enhance all of America's Memory.

Call the president warn him of our impending PTSD epidemic! Seriously people need to stop with this "research will be bad for everyone."
not rated yet Dec 25, 2009
"That's the elegant scientific finding that comes out of this."

It was not their elegance. It was just a finding.
not rated yet Dec 26, 2009
sciencebee: I think that(geriatric)memory enhancing drugs are already big sellers. For example, check out: Exelon, Aricept and Reminyl. There may be others.
5 / 5 (1) Dec 26, 2009
When will these drugs just become another "performance enhancing drug?" Students will use them to cheat on tests, as well as, those that cheat on chess or card games, and on and on and on.

There will be no reason to worry about whose muscles are greater or who hits a hardball further! Since everyone will be able to cheat in school, who cares about sports!
not rated yet Dec 26, 2009
I don't see increasing our capabilities as cheating at all. I've always told my wife the moment I can upgrade my brain so to speak I'm taking a loan out on our house. I'm not kidding. We go to school to learn. If we can learn faster I believe that is the ultimate goal. The world would change so much if it was easy to learn another language for example(and I mean very easy). It's true memory intelligence but a good memory is something 'smart people' tend to have in common. For me, I love to solve problems. I go to bed at night thinking of problems but I forget things constantly. I know everyone is different but for me, increasing our intelligence is a major goal. The heck with making "smart computer overlords". Humans are to jealous to give all the smarts to something other than ourselves. I wouldn't worry about the sifi AI robots personally.

(edit - one could also say people who wear glasses like my wife and parents also 'cheat' on tests. I'm all for making us better)
not rated yet Dec 27, 2009
FWIW, I have an inquisitive, 'pack-rat' memory, but I sometimes have problems keeping different scientific eras' info in order. ( Remember when quarks and the BigBang were outrageous whimsy ??)

IMHO, unless students taking memory boosters are specifically taught how to learn, how to question and 'grow' their knowledge, they may be trapped by superceded dogma...

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