Talk:Long-term potentiation

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[edit] Definition of Associative LTP

The definition of associative LTP was dead wrong, so I corrected it. January 27, 2006.

For the record, I think you misinterpreted that section as defining "associativity" as it pertains to LTP. Sorry for the confusion. My original intent was to distinguish between the associative LTP that occurs at CA1 synapses and the non-associative LTP that occurs in the mossy fiber pathway. I no longer see that as an important distinction that needs to be on this page, so it's since been removed. --David Iberri (talk) 17:37, 9 April 2007 (UTC)

[edit] Don't Like First Sentence

The first sentence sounds like LTP means something to do with physical strength. I think it should be changed but can't think of what to. --Username132 (talk) 19:50, 21 May 2006 (UTC)

I agree, and unfortunately I can't think of a great alternative either. For now, I've changed "long-lasting strengthening of the connection" to "long-lasting enhancement of the synapse". Though now that I think about it more, I don't like this either. You don't enhance a synapse, you enhance the strength of a synapse. Gah. Let's think about this some more... --David Iberri (talk) 14:08, 31 May 2006 (UTC)
How about:
LTP is the long-lasting enhancement in the activity efficacy of a synapse between two neurons.
? --David Iberri (talk) 16:56, 2 June 2006 (UTC)
"Efficacy" to do what? Without using concepts not yet defined. DCDuring 03:29, 6 September 2007 (UTC)
Fair enough. What do you think of the current lead sentence?
In neuroscience, long-term potentiation (LTP) is an increase in the strength of a chemical synapse that lasts from minutes to several days.
--David Iberri (talk) 11:23, 6 September 2007 (UTC)
I agreed with the original objection to the word strength. Without qualification most readers who need a reference to LTP (like me) would probably think of some kind of mechanical concept of stength. DCDuring 11:29, 6 September 2007 (UTC)
I see your point, but I'm still having a difficult time relating the concept without too much verbiage. Do you have any suggestions? (Meanwhile, I've moved your comments about inconsistencies in the lead to the bottom of this page.) --David Iberri (talk) 11:52, 6 September 2007 (UTC)

I think this might strike the right chord. I'm going to replace the lead sentence with this:

In neuroscience, long-term potentiation (LTP) is a persistent increase in the chemical strength of a synapse that lasts from minutes to several days.

Comments welcome. --David Iberri (talk) 20:37, 7 September 2007 (UTC)

Having read some of the linked articles, I am no longer the perfectly naive reader although still very naive. I think I am looking to hook up my layman's model of the brain to what this article says. Is it the
  • probability of or
  • strength of
a signal being carried across a synapse that is associated with an increase in chemical strength? I think the educated layman believes that signals are transmitted through "nerves" and that that is part of how the brain works. The objective would be to correct or improve this kind of thinking without forcing the fellow to talk a course -- or even to read the whole article. DCDuring 21:31, 7 September 2007 (UTC)
I agree, but I'm not sure all the details belong in this article. For example, there are several ways to increase the strength of a connection between neurons; off the top of my head: 1) put more neurotransmitter vesicles in the presynaptic cell, 2) make more vesicles available in the readily releasable pool, 3) increase the probability of presynaptic vesicle release, 4) increase the number of neurotransmitter receptors on the postsynaptic cell, 5) increase the efficiency with which neurotransmitters trigger electronic or metabolic events in the postsynaptic cell, or 6) increase the number of synapses between the pre- and postsynaptic cell. These (and more) should be listed in our article on synaptic strength, but probably aren't (seeing as that page currently redirects to a section within the chemical synapse article). They probably don't belong on the LTP article because not all of these mechanisms are believed to be used during LTP expression.
As for relating a layman's model of the brain to a physiological one, that's also going to be difficult to accomplish in an article on LTP. It should probably be covered in synaptic transmission, with relevant details included in the articles on chemical synapses and action potentials. Do you think specific points deserve mentioning here though? If so, let's brainstorm. PS: I just finished a major revamp of the section on mechanisms, including some specific mention of ways to improve synaptic strength (eg, increase probability of vesicle release, increase postsynaptic sensitivity to receptor). If you have a spare moment, I'd love to hear your thoughts on it. Cheers, David Iberri (talk) 07:24, 8 September 2007 (UTC)
I think the first sentence of lede has to be very simple, with the lede as a whole suggesting, but not exemplifying the level of complexity of the full article. It also may pay to give the reader some idea why the article is important. If there are numerous candidate mechanisms that might be involved, that would not be the road to simplicity. The road to simplicity might lie in emphasizing the importance of LTP mechanisms for understanding the physiological basis for human memory. As an example of the kind of bridging that I am seeking: The word "Habits", which has a long heritage in both ordinary language and in psychology and pre-psychology was hijacked by behaviorists on WP who insisted that it was all just habituation. The habituation article had very little in it that provided anything of value from the point of view of anyone linking to the term habit. I am trying to create a bridging article that fits my views about readers. You don't need the bridging article, I don't think, but you do need to keep the article from being entirely irrelevant to lay readers. I will carefully examine the other article that you refer to. DCDuring 13:20, 8 September 2007 (UTC)
Great points, all of them. After editing the mechanisms section last night, I realized that the lead was quite a bit more distinct from the rest of the article than it should be. Like you suggest, the lead should give a better overview of LTP rather than carrying out a discussion of it that isn't elaborated upon within the main article text. If you have specific changes in mind, please be WP:BOLD and go for it! --David Iberri (talk) 15:52, 8 September 2007 (UTC)
There is a disconnect between the ordinary notion of memory as soemthing that can last years and lab-demonstrated LTP lasting only days. Explaining why lab LTP differs from naturally occurring LTP would help. Is it believed that the LTP has to be maintained over longer periods by repeated stimulation to give us long-lasting memories ? DCDuring 13:40, 8 September 2007 (UTC)
That question brings up a good point that needs to be explicitly said in the article: LTP decays with time. So yes, repeated stimulation is believed to help support robust LTP. Another consideration is that one memory doesn't equal one synapse undergoing LTP; what we commonly consider a memory is probably the cumulative effect of having LTP at many synapses (thousands, millions?). With time, repeated exposure, training, etc., the weights (ie, strengths) of these synapses get fine-tuned via changes in LTP. This helps explain the disconnect between LTP in the lab (where researchers typically study at most a few dozen or hundred synapses) and memory in living animals. For example, let's take a look at a few of those synapses whose strength was increased when you learned that new memory. Now let's say that that synapse represents a relatively insignificant piece of the memory you formed. Maybe you were taught what a pickup truck looks like, and your initial memory of it made a big deal out of the fact that the wheels were separated by almost exactly one meter. Of course, not all pickup trucks have wheels separated by exactly one meter, so that fact probably needs to get refined in your memory of a pickup truck. The synapses that represent that detail thus need to be weeded out of that memory. With repeated exposure to pickup trucks, and subsequent realization (unconscious or otherwise) that the wheels aren't separated by one meter, those synapses get pruned out. Either LTP decays in these synapses, or they undergo LTP's sister process, long-term depression which decreases synaptic strength. Either way, those unimportant synapses get pruned out of your memory of pickup trucks. I gather that much of these observations are difficult to reproduce in a laboratory setting for several reasons, not the least of which being that memories are so diffusely stored in the brain (eg, what we consider a single memory might be stored in synapses in every area of the cerebral cortex). This is becoming a bit long-winded, I apologize. But hopefully you can begin to see the difficulty in relating some of this in this article. Thanks for your feedback; it's been most helpful. --David Iberri (talk) 15:52, 8 September 2007 (UTC)

[edit] Am I right to include Timothy Bliss as a co-discoverer?

I googled that Tim Bliss was a co-discoverer of LTP, and included him in the sentence about the discovery in 1966, but now I have doubts. If I was wrong, -revert my change. --CopperKettle 04:36, 12 August 2006 (UTC)

Most researchers I've spoken with (which admittedly isn't many) seem to regard Bliss as a co-discoverer, but they base that on the 1973 Bliss & Lomo paper that first characterized LTP. But based on Lomo's recent paper on the discovery of LTP, I'm fairly certain that Lomo made the initial discovery by himself in 1966, with Bliss joining the Andersen lab only in 1968. I'll revert your change for now, but feel free to continue the discussion here. --David Iberri (talk) 14:03, 12 August 2006 (UTC)

[edit] Behavioral memory

This one's just screaming to be added to the "relationship to behavioral memory" section: Whitlock J, Heynen A, Shuler M, Bear M (2006). "Learning induces long-term potentiation in the hippocampus". Science 313 (5790): 1093-7. PMID 16931756.  --David Iberri (talk) 04:28, 15 January 2007 (UTC)

Done, although it could use some refining. --David Iberri (talk) 19:26, 5 February 2007 (UTC)

[edit] Hippocampal anatomy

Jacobp22 (talk · contribs) recently added a brief description of hippocampal connectivity. It's good, but doesn't currently relate enough to LTP, so I've removed it for the time being and copied it here:

Located in the temporal lobe, the hippocampal formation is a specialized region of the limbic cortex. Believed by scholars to be associated with learning and memory, the hippocampal formation receives its primary input from the entorhinal cortex. The axons of these neurons then pass through the perforant pathway and go on to form synapses with granule cells located in the dentate gyrus.

I can see this being used in a section on LTP experimental design, which might describe why the hippocampus was used in early studies, why it is important to memory in general, and why it is important to LTP specifically. The answers to all these questions have to do with hippocampal function, which is so deeply tied to its anatomy that such a section would merit a description of the latter. Cheers, David Iberri (talk) 15:49, 10 April 2007 (UTC)

[edit] Comments

  • The caption of the first image is too long, it is longer than the introduction!
  • Reference 23 is missing.
  • Adding more "Main article" links in subsections would help guide readers to other relevant articles.

Hope this helps. TimVickers 04:49, 11 April 2007 (UTC)

Definitely helpful; thanks. I've tightened the first image caption, moving the bulk of the text to Image:LTP exemplar.jpg. I've also fixed the oversight in ref 23 -- thanks for catching it. I agree about the main article links; I'm starting a Retrograde signaling in LTP section as a start (haven't submitted it yet, though). Any additional comments are much appreciated! Cheers, David Iberri (talk) 06:59, 11 April 2007 (UTC)

[edit] Duration

hwo long does LTP last?

This is covered in the introduction to the article. --David Iberri (talk) 18:59, 27 May 2007 (UTC)

[edit] Late Phase Clarification

Awesome article. Can someone craft the last paragraph in "Late Phase" to be a bit more pedestrian? I'm a bit lost. http://en.wikipedia.org/wiki/Long-term_potentiation#Late_phase —Preceding unsigned comment added by 76.22.5.47 (talk) 02:13, 2 September 2007 (UTC)

I took a look at that section and noticed that there's quite a bit on synaptic transmission mentioned there. But as the basics of transmission are covered in the background section, I'd imagine that's not too far out of the scope of this article. Are there specific points you'd like to be clarified? --David Iberri (talk) 03:45, 3 September 2007 (UTC)

[edit] Inconsistencies

Other comments: on the lede. There are a couple of inconsistencies that bother me. Sentence 1 says LTP lasts minutes or hours vs. Later in same paragraph LTP has to do with long-term memory Sentence 1 says minutes or hours vs. paragraph 2 says years. DCDuring 11:37, 6 September 2007 (UTC)

There's a distinction drawn between LTP observed in vitro (done in hippocampal slices, cell cultures, etc.), and LTP in vivo (observed in living animals). In vitro studies have only been able to demonstrate LTP that lasts up to several hours, while in vivo studies have observed LTP lasting for many months. --David Iberri (talk) 11:50, 6 September 2007 (UTC)

[edit] Lead rewrite

In light of the recent discussion about overcomplexity of the lead, the lack of continuity between it and the main article body, etc., I've rewritten the lead mostly from scratch. I wound up dropping the paragraph on in vitro and in vivo observations (which unfortunately was the only spot that mentioned a difference in duration between LTP in vitro and in vivo), but this will be added in elsewhere, and shortly. I took some care to be upfront about the mechanisms of enhancing synaptic strength, and what it means to improve the strength of a synapse. Hopefully this is a step in the right direction. Comments welcome. --David Iberri (talk) 02:00, 20 September 2007 (UTC)

[edit] PKMz and retrograde amnesia

I've got a question about the assertion that PKMζ inhibitors cause "Retrograde Amnesia" in the paragraph about Late-LTP. Shouldn't this be anterograde amnesia? Otherwise we should be talking about an inability to recall memories with the inhibitors. TDumbarton (talk) 20:55, 18 November 2007 (UTC)

We are talking about an inability to recall memories after adminitering the PKMz inhibitor. That's exactly what the section on L-LTP maintenance is trying to convey. The gist is that PKMz is necessary/sufficient for maintenance of L-LTP and the persistence of long-term memories. PKMz inhibition interferes with the persistence of memories resulting in loss of established long-term memory: retrograde amnesia. It's important to distinguish between the acquisition of memory and the persistence of memory. PKMz appears to have no role in the acquisition of memory, only its persistence. Inhibiting PKMz does not interrupt memory acquisition, so it does not cause anterograde amnesia. See also PMID 16931766. --David Iberri (talk) 16:18, 21 November 2007 (UTC)

[edit] GA Review

This article is very well written, well referenced, and meets all of the Good Article criteria. I'm almost at a loss as to make suggestions on how to improve it, though there are a few areas that could use some additional citations (e.g. the last 2.5 paragraphs of 'Synaptic tagging' -- "There is some evidence...", and 'Relationship to behavioral memory'). Other than that, this article is excellent. Good work! Dr. Cash (talk) 17:27, 9 December 2007 (UTC)

Sweet. Thanks so much for reviewing this, Dr. Cash. I'll see about adding some more references for the sections you mentioned. Thanks again, David Iberri (talk) 00:09, 19 December 2007 (UTC)

[edit] Recommended addition of synapse-specific LTF topic

Surprised this isn't mentioned or cited: Si, K. et al. (December 26, 2003). A neuronal isoform of CPEB Regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. Cell, Vol. 115, 893-904.

Quick review: http://psychologyreview.blogspot.com/2008/02/neuronal-cpeb-stabilizes-synapse.html

--128.208.35.237 (talk) 21:52, 12 February 2008 (UTC)

[edit] Properties of LTP

I don't agree with the first property of Rapid induction. There are no references and the description sounds very much like Posttetanic Potentiation (PTP). PTP is distinctly different from LTP (please refer to Principles of Neural Science, Kandel and Jessel). PTP can last up to about an hour but is not LTP since though it is Ca2+ mediated, it does not involve phoshorylations or Kinases. As is my understanding, firing a high frequency volley through a neuron cannot IMMEDIATELY set up a LTP. It takes a couple of seconds for the cascades to work... at the bare minimum. PTP however is immediate, since it functions on residula Ca2+ from the last stimulation. User: Mubinchoudhury —Preceding unsigned comment added by Mubinchoudhury (talk • contribs) 11:19, 6 May 2008 (UTC)


Sorry... additional note. Furthermore Bliss and Collingridge, 1993 (don't remember the full reference)reported that short trains of high frequency stimulation caused synaptic potentiation. The key concept is that one train was not enough... so a brief tetanus cannot cause LTP. There are possible physiological reasons why more than one stimulation is required, that I shan't go into. User: Mubinchoudhury —Preceding unsigned comment added by Mubinchoudhury (talk • contribs) 11:26, 6 May 2008 (UTC)

Thanks for the input. By all means, be bold and correct the article (providing relevant references, of course) as you see necessary. Much thanks, David Iberri (talk) 23:32, 6 May 2008 (UTC)