If the cell's genome is altered in memory,then either all the synapses of the neuron are altered or,alternatively,some mechanism exists that enduringly restricts the effect of the new gene product(s) to selected synapses.Both assumptions are problematic.Altering all the synapses following experience-dependent modification of only part of them,seems to be a wasteful way of managing storage capacity.On the face of it the second possibility,namely selective deposition of gene products in individual synapses, is more appealing,and is substantiated by pieces of circumstantial evidence.Polyribosomes in neurons are selectively positioned beneath synaptic junctions,hence providing individual synapses with a protein synthesis machinery (Steward and Levy, 1982).Moreover,dentrites contain a cytoskeletal system for the selective transport of RNA to synaptic sites (Davis et al.1987).However,if novel RNA,or ribosomes,or proteins,are funnelled into only selected synapses,then what marks these synapses in the first place? And if such a primary long-term change occurs in the synapse,why is gene regulation needed at all?
_________________
Fausto Intilla
(Inventor-scientific divulgator)
www.oloscience.com
http://upload4.postimage.org/1299907/Faustopic.jpg (http://upload4.postimage.org/1299907/photo_hosting.html)

Ha!
My my.
The little game player Fausto Intilla.

Might as well just give up, Mr. Fausto.
Your game playing will go far less well received here than in the other forum. This forum is full of people that bite.

You could probably make a career out of posting in pseudoscience though.


For anyone reading this, Fausto is a cut and paste artist. I came across him in that other forum (some of you know where I mean) and he's confessed that he's just playing games and whatnot. I really don't understand his concept of game, seems more like he's trying to garner respect where respect isn't deserved. Intellectual fraud.
But he calls it games.

You can try to elicit a response from him, but he refused to respond at the other forum. Instead, he simply cuts and pastes more tangled jargon. Meant to impress, I'm sure.

Heh.
I guess he also had a row over at the Italian wikipedia. Plagiarism, don't you know.

But, don't let me stop you from biting him yourself.
Test him yourselves.

...as you can see,in some Forum people understand me (WHY?):

http://www.sciencechatforum.com/bulletin/viewtopic.php?t=3055

I understand you just fine. I replied to this thread in the other forum, remember?
But you seemed incapable of response.

Are you now saying that you didn't plagiarise it?
Are you now saying that you do understand the material and aren't merely perpetrating intellectual fraud?
If so, then why didn't you state as much at the other place when put to the question?
Why didn't you respond to my response to your thread and the questions that I had about it (which I have wondered if english as a second language might not share some part in.)

Should I then copy-paste my response over here to allow you to respond?

There are also a few people on this forum who are far more versed in this area of science than I and they would be able to go over this in far finer detail than I.

Do you actually want to discuss the topic or do you not?

I will take back everything I've said about you should you prove me wrong.
My theory about you is merely based on your actions and the very words you said about yourself.

Don't worry invert. It's not like there is anyone serious left to respond to this crap.

what... are all the serious poster gone, when did this happen

btw, did you know when you slice onions sulfenic acids a formed, these acids then quickly changes form in to a gas, when the gas then comes into contact with the water in the eye it reforms into a mild sulfenic acid again and that is the reason your eyes sting when cutting onion.

I actually didn't know that. I thought it was because onions haddle little elves on them that shoot you with arrows.

no, that would be cabbage all kinds of cabbage. Eleves, those evil leaf lovers are attracted to cabbages because they are oooh so good and they will defend them with there lives.

Now you might say that "but it doesn't hurt my eyes when i cut cabbage" and that is also true, but that is because elves are terribly inefficent in hurting people primarely do to there small size and belive in "all thinngs most coexist in blissfully harmony" mantra which, luckly for us, leads to there quick and eminent death.

I always knew Lord of The Rings was a fake documentary. Like an elve could kill an Orc. Or a garden gnome for that matter.

yea to think hobbits are the good guys, they are the personification of evil

indeed. big hairy feet. Eating mushrooms all the time.

Need i say more?

Sooo, hobbits are in fact Dutch?

well they could be excepts that dutch are born with bicycle wheels, it's first as the grow older that there wheels mutate in to normal legs, kinda lige some fish change apperance, but then again Holland is below sea level

Don't worry invert. It's not like there is anyone serious left to respond to this crap.

That's not actually true, Spurious.

Look. Charonz showed up to the party.
Hercules is still around from time to time as well.
Umm. I guess them and you are the only ones who really have much microbiological know-how... Used to be more. But, like you say, they don't come around anymore....

Anyway, the opening post isn't completely crap although it is vague about certain issues. At least one of the papers referenced is real.

My question is is the opening post actually Fausto's work or did he plagiarize it? I tend to believe it is his work because of the confusing nature of it. If he plagiarized it, you'd think it's be a bit more clear and less obfuscatory.

The main problem with the post is that it seems to be talking about some form of genetic memory or something... I'm not entirely sure, actually. I asked him about it in that other forum but he never answered...

Fuck it.
I'll repost it here just for good measure:

=======================



Polyribosomes in neurons are selectively positioned beneath synaptic junctions,hence providing individual synapses with a protein synthesis machinery (Steward and Levy, 1982).

Technically, the paper states that polyribosomes are preferentially found at the base of dendritic spines or mounds (which are then conjectured to be part of the base of a dendritic spine).

And, the area of the brain mentioned is the dentate gyrus of the rat brain.


However,if novel RNA,or ribosomes,or proteins,are funnelled into only selected synapses,then what marks these synapses in the first place?

Good question. But probably answered by the same mechanism which marks the destination of any protein. Although, there would seem to be a larger number of addresses needed for the huge number of dendritic spines.

However, each spine need not be uniquely addressed. Perhaps they are separated into groups of some sort?

Interesting line of research.

But what of the axonal side of things?

And what of soma synapses?


And if such a primary long-term change occurs in the synapse,why is gene regulation needed at all?

This and:


If the cell's genome is altered in memory,then either all the synapses of the neuron are altered or,alternatively,some mechanism exists that enduringly restricts the effect of the new gene product(s) to selected synapses.

Are probably the two most difficult things to understand about your post (aside from the tangled jargon, of course.)
What does 'If the cell's genome is altered in memory' mean?
And why wouldn't you expect gene regulation in synapses?

Seems to me that the polyribosomes might serve several purposes.

For one, the dendritic spines shift about quite often and the polyribosomes would likely create the protein machinery to regulate this whole process (although I wouldn't be suprised to find more than simple RNA and proteins involved. miRNA and the like probably play key roles as well.)

It seems to be more efficient to have the machinery in place rather than to necessitate the physical transport of multiple proteins and etc when changes need to be made. This way, only RNA of various flavors need be transported en masse.

Still. Addressing is a problem.

Interesting line of thought.

A pity you couldn't try stating these things in ordinary language.

Question: Is this your work or did you copy it from a journal somewhere?


Furthermore,structural alterations may then occur retrogradely from the synapse towards the cell body,directing the transport of newly synthesized mRNA or proteins only to the modified synapse

Structural alterations such as...?


Finally,the possibility that synapses have autonomous DNA,for example in mitochondria,should not be neglected.

A novel notion. But one which would surely have been discovered by now, I should think. Still something to look into. I would doubt that every synapse could have its own DNA overlord, but perhaps a few key junctures might have its own DNA which would ease the strain of addressing problems.

This would be a huge change in cellular function. A huge paradigm shift.

Unlikely. But an interesting notion.




Couldn't find the Davis et al paper.
But the other one is here: http://www.jneurosci.org/cgi/content/abstract/2/3/284

Might as well throw this in for good measure:

http://www.sciencemag.org/cgi/content/summary/313/5794/1744
http://www.sciencemag.org/cgi/content/abstract/313/5794/1792

The first is a summary and the second is the abstract for a paper in the issue of Science I'm currently reading (the issue before the most current).

It talks about a couple of post-synaptic proteins and their functions. Connecting them to some types of epilepsy.

It makes no mention of memory, of course, nor does it mention where the proteins are constructed. In the body of the cell or in the dendritic spine. Nor does it mention how the proteins are delivered to the specific location it is needed.

That is what is most interesting to me about the opening post. The question of addressing. In neurons, this problem is magnified hugely compared to ordinary cells. Because of this, it makes sense that ribosomes would be found in the dendrites. This still leaves us with problems of addressing for the mRNA however. And the tRNA would also have to filter down there....

As I said, an interesting line of study and one which had previously escaped my attention.


But, to link any of this with memory is quite tenuous.
Perhaps if Fausto was able to actually explain his model of memory? That is something that is sorely missing from the opening post. Perhaps its a common model which I am not familiar with?

well they could be excepts that dutch are born with bicycle wheels, it's first as the grow older that there wheels mutate in to normal legs, kinda lige some fish change apperance, but then again Holland is below sea level

That would make him a Wheeler!

http://img122.imageshack.us/img122/8959/wheelerpackal9.jpg

Better than a Gump, I suppose.

http://img122.imageshack.us/img122/4411/gumpwj1.gif

Have you seen this?
http://www.sciencedaily.com/releases/2006/01/060114233355.htm



"It has been known for some time that learning and long-term memory require synthesis of new proteins, but exactly how protein synthesis activity relates to memory creation and storage has not been clear," says Sam Kunes, professor of molecular and cellular biology in Harvard's Faculty of Arts and Sciences. "We have been able to monitor, for the first time, the synthesis of protein at the synapses between neurons as an animal learns, and we found a biochemical pathway that determines if and where this protein synthesis happens. This pathway, called RISC, interacts with RNA at synapses to facilitate the protein synthesis associated with forming a stable memory. In fruit flies, at least, this process makes the difference between remembering something for an hour and remembering it for a day or more."

Here is another that looks interesting (its older):

http://www.sciencedaily.com/releases/2002/01/020104074521.htm


"We just don't find neurons that are generic memory neurons. What we find are neurons that show statistically significant relationships to memory for a particular thing," Ojemann says.

There are three regional differences in brain activity that have not been noted before:

* There is a cluster of neurons that changes activity from encoding, to storage, to retrieval, in the basal temporal area, below the temporal lobe.

* Neurons that may help people recall something quickly after they have seen it earlier in the day what scientists call 'implicit memory' -- seem very active in the superior temporal gyrus of the temporal lobe.

* There are neurons in the language-dominant hemisphere that respond to more than one modality memory of both visual and auditory material.

At this point, the research is helping to illuminate the vast mysteries of the human brain. Someday, scientists may be able to use this knowledge to assist ailing brains. For example, it may be possible to externally activate neurons related to memory encoding in order to enhance memory.

By golly, there's Sam to the rescue!
Thanks, Sam. Interesting stuff. I'm going to go look at those in more depth now.

RISC... hmm. Isn't there a RISC architecture for the computer?
The name rings bells, but I'm unsure whether it's the computer or the microbiology bell that's being rung. PRobably the former.

By golly, there's Sam to the rescue!
Thanks, Sam. Interesting stuff. I'm going to go look at those in more depth now.

RISC... hmm. Isn't there a RISC architecture for the computer?
The name rings bells, but I'm unsure whether it's the computer or the microbiology bell that's being rung. PRobably the former.

Here is the original paper:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16413491&query_hl=3&itool=pubmed_docsum

can you access it?

Alas. No.
I only have Science, I'm afraid.

Alas. No.
I only have Science, I'm afraid.

Okay.

This is the approach and model:

A well-defined system for the study of memory is the olfactory/electric shock paradigm of Drosophila (Tully and Quinn, 1985). A memory of odor associated with electric shock can be induced in phases that include short-term (STM) and long-term (LTM), phases that are distinguished by their dependence on training protocol, genetic pathway, and protein synthesis. A requirement for protein synthesis in olfactory LTM was demonstrated long ago (Tully et al., 1994) and reinforced by the identification of longterm memory mutants as genes with functions in mRNA transport and translation (Dubnau et al., 2003). This system presents an opportunity to determine how and where protein synthesis is deployed and what mechanisms regulate it during the formation of a memory.

To approach these questions, we devised fluorescent reporters of synaptic protein synthesis using sequences of the Drosophila Calcium/Calmodulin-dependent Kinase II (CaMKII), the homolog of the mammalian αCaMKII, which is synthesized at synapses and required for memory (reviewed in Kelleher et al., 2004). We show that the induction of a long-term memory in Drosophila is accompanied by transport of mRNA to synapses and patterns of synaptic protein synthesis that have features of memory specificity. These events are regulated by components of the RNA interference (RISC) pathway. At least one RISC factor, Armitage (Cook et al., 2004), is localized to synapses and degraded by the proteasome in response to neural activity or the induction of an LTM. Therefore, degradative control of RISC underlies the pattern of synaptic protein synthesis associated with the establishment of a stable memory.

Here's another general article on the same research:

http://www.news.harvard.edu/gazette/2006/02.02/35-kunes.html

...the RNA interference (RISC) pathway

Derr.
That's where I know RISC from.


...patterns of synaptic protein synthesis that have features of memory specificity.

I wonder exactly what and how these proteins are utilized. Are they the framework of the dendritic spines? Are they part of the cytoskeleton of the dendrites?

This does take place in the dendrites, yes? Not the axon?

Interesting stuff, but I'd like to see a more explanatory model. I suppose it's rather early in the game yet...
It's a start though.



By manipulating the RISC pathway, Kunes and colleagues were able to alter flies' memory, changing their response to stimuli in subsequent behavioral tests. Using a classical learning test that simultaneously exposes the insects to an odor and an electric shock, the researchers found that long-term memory could be greatly increased by adjusting the activity of the RISC pathway in the fruit flies.

"In essence, these flies had twice the memory of their normal counterparts," Kunes says. "When RISC was knocked out, so was long-term memory, and flies would remember to alter their behavior in the presence of the shock-linked odor for perhaps an hour; that is, they only had short-term memory. When the pathway was normally active, the flies remained averse to the odor for a day or more."

Alright.
So.
What we have here is that the mRNA that is translated into proteins that get somehow utilized in memory incorporation are sent down the dendrites willy-nilly. Little to no direct addressing.

At the sites where memory incorporation is occurring, the RISC factor Armitage (among others) is removed and thus the mRNA is able to be translated at these sites into the necessary proteins.

That's pretty simple.

And when RISC is knocked out completely, I'm thinking, then LTM is eradicated as the mRNA being sent down the dendrites is being translated everywhere (although it might well be getting used up in the dendritic spines closes to the soma and never reaching the outlying reaches.

This effect, I would think, would have a large number of side effects other than a disappearance of LTM. Unless I'm conceiving this wrong.


I'd really like to know how the proteins are utilized in incorporating a memory. The only thing I can think of is by making temporary synapses permanent.... Hebbian learning at its finest....

Interesting stuff, really.

Thanks, Sam.

Long-lasting memories are stored in the brain through strengthening of the connections, or synapses, between neurons. Researchers have known for many years that neurons must turn on the synthesis of new proteins for long-term memory storage and synaptic strengthening to occur, but the mechanisms by which neurons accomplish these tasks have remained elusive.

So. Pretty much what I conjectured above.

However, this is still crude and lacks a truly effective model.
For instance, how is it that synaptic structure of the neural network translates to memory? This is a key discovery waiting to be made.

Getting closer though.

So. I suppose.. Back to proteins.
The proteins are probably many.
Some proteins go into the cytoskeleton.
Some proteins go into the ion channels.. although. No. that wouldn't work unless there was an endoplasmic reticulum at the synapse as well. And I seriously doubt this. So, ion channels and other membrane proteins would have to be transported all the way from the cell body.

This brings up addressing again, because the specific membrane proteins must be delievered to the specific synapses in order to be effective.

Anyway.
There's a whole host of proteins and uses of proteins that can be made in situ.
But, still, transmembrane proteins put a crimp in this particular model...

Hmm.


Edit:

ahh.


An immediate question that Tonegawa and colleagues are pursuing is how neurons target the newly synthesized proteins to the specific synapses participating in memory formation while not modifying other synapses.

Heh heh heh.
Yup. That's the thing, eh?

Looks like these guys aren't talking about the same protein pathways as the others. This pathway (MAPK) seems to be targeted towards the ordinary somatic protein synthesis.

I imagine that it probably takes part in the RISC option as well.

It would be interesting to see the differences in proteins utilized by these two separate pathways.
I suppose one 'obvious' would be that membrane proteins would, by necessity, be part of the MAPK pathway rather than being created in situ via RISC.

But what other categories of proteins are involved in LTM?

And, in this model, is STM merely the temporary formation of the neural network which will vanish within hours if not strengthened and made permanent via protein synthesis?

And what about working memory?

How do these physical models combine with the psychological models?

Ah.
What an era looms on the horizon.
FINALLY.

Ample evidence indicates that the expression of genes in the mature organism is influenced by the environment.It is ,therefore,tempting to consider a role in memory for alteration in gene expression.Before proceeding to discuss experimental evidence for the macromolecular synthesis hypothesis,I should clarify what role the newly synthesized proteins could have.I assume that these proteins modify properties of neuronal systems,by stabilizing and extending mechanisms used in short-term memory,or by initiating new types of cellular change.Note that the neuronal loci subserving short - and long - term memory are expected to overlap,at least at first,but need not be identical.An example from Aplysia illustrates this:
short term habituation of the GSW reflex was portrayed as homosynaptic depression,but long-term habituation involves additional central neurons and heterosynaptic depression(Montarolo 1988).However,regardless of wich cellular loci are modified in short and long term memory,one point is clear: macromolecules subserve changes in the representational properties of neuronal circuits,but do not directly encode a specific representation.The latter is encoded in the connectivity and molar activity of the circuit.In other words,similar molecular changes may subserve different modifications in different internal representations,depending on the cellular context in wich these molecular changes take place.

Fausto Intilla
www.oloscience.com

Ample evidence indicates that the expression of genes in the mature organism is influenced by the environment.

Only in specific cases and hence the whole discussion that follows is pointless. You will have to address the specific cases.

...as you can see,in some Forum people understand me (WHY?):

Funny, the link shows you were not understood.

"Fausto Intilla
(Inventor-scientific divulgator)"

What is a 'divulgator?'