LTP Research Has Done Nothing to Show Any Neural Basis for Memory Creation

In the English language "lost in the woods" is a phrase meaning "to be confused, bewildered or helpless." Neuroscientists trying to explain how human beings create memories have always been very much lost in the woods. Such scientists have no credible tale to tell on this topic. The problem is that nothing in the brain bears the slightest resemblance to some apparatus for storing learned information. Humans create various types of devices for writing information, things such as pens, pencils, paint brushes, typewriters, laser jet printers, offset printers, and the read/write heads used by a computer hard drive. Nothing in the brain bears any resemblance to such things. 

So what do you if you are a neuroscientist trying to fool people into thinking that neuroscientists like yourself have some kind of understanding of how a human could form a memory? What such people normally merely do is to senselessly repeat the same old clueless charade that neuroscientists have been doing for about fifty years: they zap a tiny bit of brain tissue, creating some tiny change that lasts about as long as a suntan or the morning dew, and they try and pass off that little change as something like information storage, even though no information was stored. This is the witless nonsense of LTP experiments. 

What is misleadingly called “long-term potentiation” or LTP is a not-very-long-lasting effect by which certain types of high-frequency stimulation performed by scientists (such as stimulation by electrodes) produces a fleeting increase in the strength of synapses. The main part of synapses are gaps between nerve cells, gaps which neurotransmitters can jump over. The evidence that LTP even occurs when people remember things is not very strong, and in 1999 a scientist stated (after decades of research on LTP) the following:

"[Scientists] have never been able to see it and actually correlate it with learning and memory. In other words, they've never been able to train an animal, look inside the brain, and see evidence that LTP occurred."

In 2007 a scientist said on page 120 of her PhD thesis, "While LTP is assumed to be the neural correlate of learning and memory, no conclusive evidence has been produced to substantiate that when an organism learns LTP occurs in that organism’s brain or brain correlate."

So-called long-term potentiation is actually a very short-term phenomenon. Speaking of long-term potentiation (LTP), and using the term “decays to baseline levels” (which means “disappears”), a scientific paper says, "potentiation almost always decays to baseline levels within a week," while noting that even after considering LTP "we would be at a loss for a brain mechanism for the storage of a long-term memory."

Another scientific paper says something similar, although it tells us even more strongly that so-called long-term potentiation (LTP) is really a very short-term affair. For it tells us that “in general LTP decays back to baseline within a few hours.” “Decays back to baseline” means the same as “vanishes.” 

Neuroscientists have long been guilty of profoundly misleading behavior in trying to persuade people that so-called so-called long-term potentiation (LTP) is a "mechanism for memory." Inducing LTP requires artificial electrode stimulation which synapses do not naturally receive.  Also, human memories can last for sixty years, but LTP is a very short-lived thing.  So why do neuroscientists keep doing LTP experiments, and why do they keep mentioning LTP as if it had something to do with memory? There are two reasons:

(1) It always sounds better if you have some sound bite or catchphrase you can mutter when someone asks how something occurs, rather than saying, "I haven't the slightest idea how it occurs." When scientists can mutter the phrase "LTP" when asked about how memories are created, it makes them sound more knowledgeable, rather than sounding like people who have no understanding of a topic. 

(2) LTP research is an easy-to-conduct "no way to fail" line of research that provides an easy way for a neuroscientist to add to his total of published papers. Scientists love these kind of "no way to fail" research opportunities. Similarly, theoretical physicists keep grinding out speculative papers about string theory or primordial cosmic inflation.  If you have learned how to write such a papers, doing another such paper is a relatively easy and safe way to get another published paper. 

In a recent article in Knowable Magazine, we have a very bad article repeating "hook, line and sinker" the groundless legend that LTP research did something to show a neural basis for memory storage. The author (Tim Vernimmen)  is a freelance science journalist who as far as I can see has little history of writing on topics of cognitive neuroscience or human memory.  The article has the extremely misleading title "It began with a rabbit: Unraveling the mystery of memory" suggesting the utterly groundless boast that scientists have done something to unravel the mystery of memory -- something that is still a hundred miles over their heads. 

We read about a 1973 paper by Bliss and Lomo in which some rabbits had their brains artificially zapped after "stimulating electrodes were constructed from electrolytically sharpened tungsten wire insulated with several coats of varnish." We have a claim that the paper is "now considered a turning point in the study of learning and memory." No, it was only the opening of a dead end that has led nowhere.  Very many similar papers have been done, but LTP research has done nothing to show any credible neural basis by which memories could be formed. Vernimmen then makes this false claim: " Bliss and Lømo had discovered something momentous: a phenomenon called long-term potentiation, or LTP, which researchers now know is fundamental to the brain’s ability to learn and remember." No, researchers do not know any such thing, and LTP research has done nothing to show any neural basis for learning or memory. 

Vernimmen then makes this untrue claim: "By the early 1970s, neuroscientist Eric Kandel had demonstrated that some simple forms of learning can be explained by chemical changes in synapses — at least in a species of sea slug." No, Kandel did not show any such thing. Vernimmen is repeating one of the many groundless legends of neuroscience. We hear this myth sometimes stated as a claim that Kandel won a Nobel Prize for showing that sea slugs can learn by changes in synapses.  The official page listing the year 2000 Nobel Prize for physiology states only the following: "The Nobel Prize in Physiology or Medicine 2000 was awarded jointly to Arvid Carlsson, Paul Greengard and Eric R. Kandel 'for their discoveries concerning signal transduction in the nervous system.' " The Nobel committee did not make any claim that synapses had been discovered as the basis of memory. 

The paper in question can be read here. The paper fails to mention a testing of more than a single animal, thereby strongly violating rules of robust experimental research on animals (under which an effect should not be claimed unless at least 15 subjects were tested).  We have no reliable evidence about memory storage from this paper. If the paper somehow led to its authors getting a Nobel Prize, that may have been a careless accolade.  The Nobel Prize committee is pretty good about awarding prizes only to the well-deserved, but it may occasionally fall under the gravitational influence of scientists boasting about some "breakthrough" that was not really any such thing.  In some cases the Nobel Prize committee awards science Nobel Prizes it should not have awarded. A notable case (the case of Christian Anfinsen) is discussed in my post here, which notes misstatements in one year's press release for a Nobel Prize. 

Vernimmen then spends several paragraphs discussing techniques of Bliss and Lomo, and then makes the following laughable statement:

"After a few brief periods of high-frequency stimulation, the oscillations would become more pronounced for up to 10 hours, indicating that neurons in the rabbit’s hippocampus responded more strongly — an enduring change that would later become known as long-term potentiation. This looked a lot like the kind of activity many scientists suspected to be at the root of learning and memory."

There are three things very laughable about this statement: 

(1) The attempt to claim that some utterly artificial technique involving zapping a rabbit with electrodes might be "the kind of activity many scientists suspected to be at the root of learning and memory." People are not zapped with electrodes when they learn. 

(2) The misleading use of the word "enduring" to describe a very short-term effect lasting only "up to ten hours."

(3) The attempt to insinuate that this very short-lived effect had some relevance to explaining memories, which in humans can last for 60 years. 

Vernimmen then makes another incorrect statement, saying, "Neuroscientist Richard Morris showed that giving rats a drug that blocks the NMDA receptor impairs their ability to learn how to navigate a maze that untreated rats can easily figure out." No, he did not show that. A 2014 study was entitled "Hippocampal NMDA receptors are important for behavioural inhibition but not for encoding associative spatial memories." And a 2011 study found this:

"We found that inducible knockout mice, lacking NMDA receptor in either forebrain or hippocampus CA1 region at the time of memory retrieval, exhibited normal recall of associative spatial reference memory regardless of whether retrievals took place under full-cue or partial-cue conditions. Moreover, systemic antagonism of NMDA receptor during retention tests also had no effect on full-cue or partial-cue recall of spatial water maze memories. Thus, both genetic and pharmacological experiments collectively demonstrate that pattern completion during spatial associative memory recall does not require the NMDA receptor in the hippocampus or forebrain."

Vernimmen then goes into a discussion of chemical events occurring in synapses. He fails to provide any reason for claiming that any of the chemistry he discusses has anything to do with memory. Vernimmen gives us an extremely misleading visual showing four steps of synaptic transmission, the process by which chemicals pass over a synaptic gap.

His four-part visual is showing the same thing as depicted below:

Synaptic transmission

Misleadingly, Vernimmen's  visual is labeled "How memories form: the steps of LTP." Synaptic transmission is not memory formation. All of the chemicals involved in synaptic transmission are extremely short-lived chemicals that do not even last a day, and have average lifetimes of less than an hour. 

Vernimmen seems to have got very badly confused here. The groundless hand-waving claim made by neuroscientists about memory and synapses is that a memory can form by a strengthening of synapses, something requiring at least hours.  But the strengthening of a synapse is not synaptic transmission, the passing of chemicals over a synaptic gap, which occurs instantly. Also, synaptic transmission is a natural event occurring throughout the brain, while the LTP produced by electrode stimulation (as in the experiment of Bliss and Lomo) is an artificial event produced by inserting manufactured electrodes into a brain.  So for Vernimmen to have a visual describing natural synaptic transmission and to label that as "How memories form: the steps of LTP" is a very bad example of bunk and baloney. Natural synaptic transmission is neither LTP nor memory formation. Neuroscientists do not claim that synaptic transmission (the passing of chemicals across synaptic gaps) explains memory formation.  Vernimmen's diagram has a bungling caption in which a synaptic gap (the gap between two synaptic clefts) is labeled as an example of a "strong connection." When neuroscientists are talking about a strengthening of connections in brains, they mean more synapses between neurons and stronger synapses, not anything in a gap between synapses. 

Vernimmen then makes the claim that LTP causes dendritic spines to grow. The claim is irrelevant to explaining how memories form, both because dendritic spines are too-shorted lived to explain memories lasting for decades, and also because LTP produced by electrode stimulation (as in the experiment of Bliss and Lomo) is an artificial event produced by inserting manufactured electrodes into a brain, not a natural occurrence.  See my post "Imaging of Dendritic Spines Hint That Brains Are Too Unstable to Store Memories for Decades" for the evidence about the short lifetimes of dendritic spines. 

Vernimmen then gives us this passage:

" Bear and his team at MIT, for example, were the first to show that LTP is involved in the formation of fearful memories in mice. In a 2006 experiment, they trained mice to avoid a dark area where they’d previously received an electric shock to the feet. Meanwhile, they used an electrode to record how neurons in the hippocampus responded. 'Sure enough, there was LTP,'  says Bear:"

The reference is to the low-quality paper here, which does not qualify as robust research, because it used a study group size of only seven mice. And you don't show that something explains memory by showing that it exists when a memory is formed. There are endless thousands of things going on in the brain and body while a memory is formed. 

Vernimmen ends with a groundless self-serving quote by Bliss that "The weight of evidence suggests that LTP is central to the physiology of memory storage."  No neuroscientists do not have any understanding of any such thing as a "physiology of memory storage." Nothing in Vernimmen's article has substantiated the claim that LTP has anything to do with human memory.  From the standpoint of actually doing something to credibly explain human memories that can last for 50 years, research on LTP has been the deadest of dead ends. 

It seems that whoever is in charge of quality control at Knowable Magazine isn't doing a good job. Vernimmen's article had lots of false information, and at its bottom we ironically see the sight below. First, there is a link to an article with the ludicrous title "Making the case against memories as evidence." Then there is a plea for donation to the magazine, with the claim that this will "fight misinformation." Oops, it seems that our self-described "misinformation fighters" are guilty of spreading some very bad false information of their own. And clearly these guys are really, really bad at understanding memory, as they have made the utterly goofy claim that memories should not be counted as evidence. If you followed that principle, then half of the murderers in prison would be set free, basically everyone convicted because of the testimony of a witness. 

Below are some of the very many reasons for rejecting claims that human memories are formed by any neural mechanism:

• Although it is claimed that memories are stored in the brain (specifically in synapses), there is no place in the brain that is a plausible storage site for human memories that can last for 50 years or longer. The proteins that make up both synapses and dendritic spines are quite short-lived, being subject to very high molecular turnover which gives them an average lifetime of only a few weeks or less. Both synapses and dendritic spines are a “shifting sands” substrate absolutely unsuitable for storing memories that last reliably for decades.
• It is claimed that memories are stored in brains, but humans are able to instantly recall accurately very obscure items of knowledge and memories learned or experienced decades ago; and the brain seems to have none of the characteristics that would allow such a thing. The recall of an obscure memory from a brain would require some ability to access the exact location in the brain where such a memory was stored (such as the neurons near neuron# 8,124,412,242). But given the lack of any neuron coordinate system or any neuron position notation system or anything like an indexing system or addressing system in the brain, it would seem impossible for a brain to perform anything like such an instantaneous lookup of stored information from some exact spot in the brain.
• If humans were storing their memories in brains, there would have to be a fantastically complex translation system (almost infinitely more complicated than the ASCII code or the genetic code) by which mental concepts, words and images are translated into neural states. But no trace of any such system has ever been found, no one has given a credible detailed theory of how it could work, and if it existed it would be a “miracle of design” that would be naturally inexplicable.
• If human brains actually stored conceptual and experiential memories, the human brain would have to have both a write mechanism by which exact information can be precisely written, and a read mechanism by which exact information can be precisely read. The brain seems to have neither of these things. There is nothing in the brain similar to the “read-write” heads found in computers.
• We know from our experience with computers the type of things that an information storage and retrieval system uses and requires. The human brain seems to have nothing like any of these things. 
• As discussed here, humans can form new memories instantly, at a speed much faster than would be possible if we were using our brains to store such memories. It is typically claimed that memories are stored by “synapse strengthening” and protein synthesis, but such things do not work fast enough to explain the formation of memories that can occur instantly.
• Contrary to the idea that human memories are stored in synapses, the density of synapses sharply decreases between childhood and early adulthood. We see no neural effect matching the growth of learned memories in human.
• There are many humans with either exceptional memory abilities (such as those with hyperthymesia who can recall every day of their adulthood) or exceptional thinking abilities (such as savants with incredible calculation abilities). But such cases do not involve larger brains, very often involve completely ordinary brains, and quite often involve damaged brains, quite to the contrary of what we would expect from the “brains make minds” assumption.

• For decades microscopes have been powerful enough to detect memories in brains, if memories existed in brains. Very much brain tissue has been studied by the most powerful microscopes: both brain tissue extracting from living patients, and brain tissue extracted from someone very soon after he died. Very many thousands of brains have been examined soon after death.  Microscopes now allow us to see very clearly what is in the tiniest brain structures such as dendritic spines and synapse heads. But microscopic examination of brain tissue has failed to reveal any trace whatsoever of learned information in a brain.  No one has found a single letter of the alphabet stored in a brain; no has found a single number stored in a brain; and no one has ever found even a single pixel of something someone saw a day or more before.  If memories were stored in human brains, microscopes would have revealed decisive evidence of such a thing decades ago.  But no such evidence has appeared. 
• There is nothing in the brain that looks like learned information stored according to some systematic format that humans understand or do not understand. Even when scientists cannot figure out a code used to store information, they often can detect hallmarks of encoded information. For example, long before Europeans were able to decipher how hieroglyphics worked, they were able to see a repetition of symbolic tokens that persuaded them that some type of coding system was being used. Nothing like that can be seen in the brain. We see zero signs that synapses or dendritic spines are any such things as encoded information. 
• Many humans can remember with perfect accuracy very long bodies of text, but synapses in the brain do not reliably transmit information. An individual chemical synapse transmits an action potential with a reliability of only 50% or less, as little as 10%. A recall of long bodies of text would require a traversal of very many chemical synapses. A scientific paper says, "In the cortex, individual synapses seem to be extremely unreliable: the probability of transmitter release in response to a single action potential can be as low as 0.1 or lower."