A New Paper Reminds Us Neuroscientists Can't Get Their Story Straight About Memory Storage

There is a new scientific paper with the inappropriate title "Where is Memory Information Stored in the Brain?" This is not the question we should be asking. The question we should be asking is: "Is memory information stored in the brain?"  Although it was probably not the intention of the authors (James Tee and Desmond P. Taylor), what we get in the paper is a portrait of how neuroscientists are floundering around on this topic, like some poor shark that is left struggling in the sand after going after its prey too aggressively. 

Tee and Taylor claim this on page 5: "Based on his discovery of the synapse as the physiological basis of memory storage, Kandel was awarded the year 2000 Nobel Prize in Physiology or Medicine (Nobel Prize, 2000)." This is a misstatement about a very important topic. The Nobel Prize listing for Kandel does not mention memory. 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. 

Before making this claim about the Nobel Prize, Tee and Taylor  state something that makes no sense. They state, "The groundbreaking work on how memory is (believed to be) stored in the human brain was performed by the research laboratory of Eric R. Kandel on the sea slug Aplysia (Kupfermann et al., 1970; Pinsker et al., 1970)." How could research on a tiny sea slug tell us how human beings store memories?  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. 

Equally undeserving of a Nobel Prize was the next research discussed by our new paper on memory storage: research claiming a discovery of "place cells" in the hippocampus. John O' Keefe published a paper in 1976 claiming to detect "place units" in the hippocampus of rats. The paper also used the term "place cells."  The claim was that certain cells were more active when a rat was in a certain spatial position. The paper did not meet standards of good experimental science. For one thing, the study group sizes it used were way too small for a robust evidence to have produced.  One of the study group sizes consisted of only five rats, and another study group size consisted of only four rats.  15 animals per study group is the minimum for a moderately convincing result.  For another thing no blinding protocol was used. And the study was not a pre-registered study, but was apparently one of those studies in which an analyst is free to fish for whatever effect he may feel like finding after data has been collected. 

The visuals in the study compare wavy signal lines collected while a rat was in different areas of an enclosed unit. The wavy signal lines look pretty much the same no matter which area the rats were in. But O'Keefe claims to have found differences.  No one should be persuaded that the paper shows robust evidence for an important real effect.  We should suspect that the analyst has looked for stretches of wavy lines that looked different when the rat was in different areas, and chosen stretches of wavy lines that best-supported his claim that some cells were more active when the rats were in different areas.  Similar Questionable Research Practices (with similar too-small study groups such as four rats) can be seen in O'Keefe's 1978 paper here. 

Although O'Keefe's 1976 paper and 1978 paper were not at all a robust demonstration of any important effect, the myth that "place cells" had been discovered started to spread around among neuroscience professors.  O'Keefe even got a Nobel Prize. The Nobel Prize committee is normally pretty good about awarding prizes only when an important discovery has been made for which there was very good evidence. Awarding O'Keefe a Nobel Prize for his unconvincing work on supposed "place cells" seems like another flub of the normally trusty Nobel Prize committee. Even if certain cells are more active when rats are in certain positions (something we would always expect to observe from chance variations), that does nothing to show that there is anything like a map of spatial locations in the brain of rats. 

On page 7 of the new paper on memory storage, we have a discussion of equally unconvincing results:

"LeDoux found that this conditioned fear resulted in LTP (strengthening of synapses) in the auditory neurons of the amygdala, to which he concluded that the LTP constituted memory of the conditioned fear. That is, memory was stored by way of strengthening the synapses, as hypothesized by Hebb."

You may understand why this is nothing like convincing evidence when you realize that synapses are constantly undergoing random changes. At any moment billions of synapses may be weakening, and billions of other synapses may be strengthening.  So finding some strengthening of synapses is no evidence of memory formation. It is merely finding what goes on constantly in the brain, with weakening of synapses occurring just as often as strengthening. The new paper on memory storage confesses this when it says on page 8 that: "synapses in the brain are constantly changing, in part due to the inevitable existence of noise." 

On pages 8-9 of the new paper, Tee and Taylor say that scientists had hopes that there would be breakthroughs in handling memory problems by studying synapses, but that "the long-awaited breakthroughs have yet to be found, raising some doubts against Hebb’s synaptic [memory storage] hypothesis and the subsequent associated experimental findings." Tee and Taylor give us on page 9 a quotation from two other scientists, one that gives a great reason for rejecting theories of synaptic memory storage:

"If we believe that memories are made of patterns of synaptic connections sculpted by experience, and if we know, behaviorally, that motor memories last a lifetime, then how can we explain the fact that individual synaptic spines are constantly turning over and that aggregate synaptic strengths are constantly fluctuating? How can the memories outlast their putative constitutive components?"

Tee and Taylor  then tell us that this problem does not just involve motor memories:

"They further pointed out that this mystery existed beyond motor neuroscience, extending to all of systems neuroscience given that many studies have found such constant turn over of synapses regardless of the cortical region. In order words, synapses are constantly changing throughout the entire brain: 'How is the permanence of memory constructed from the evanescence of synaptic spines?' (Bizzi & Ajemian, 2015, p. 92). This is perhaps the biggest challenge against the notion of synapse as the physical basis of memory."

Tee and Taylor then discuss various experiments that defy the synaptic theory of memory storage.  Most of the studies are guilty of the same Questionable Research Practices that are so extremely common in neuroscience research these days, so I need not discuss them.  We hear on page 14 about various scientists postulating theories that are alternatives to the synaptic theory of memory storage:

"The logical question to pose at this point is: if memory information is not stored in the synapse, then where is it? Glanzman suggested that memory might be stored in the nucleus of the neurons (Chen et al., 2014). On the other hand, Tonegawa proposed that memory might be stored in the connectivity pathways (circuit connections) of a network of neurons (Ryan et al., 2015). Hesslow emphasized that memory is highly unlikely to be a network property (in disagreement with Tonegawa), and further posited that the memory mechanism is intrinsic to the neuron (in agreement with Glanzman) (Johansson et al., 2014)."

You get the idea? These guys are in disarray, kind of all over the map, waffling around between different cheesy theories of memory storage. All of the ideas mentioned above have their own fatal difficulties, reasons why they cannot be true.  In particular, there is no place in a neuron where memory could be written, with the exception of DNA and RNA; and there is zero evidence that learned knowledge such as episodic memories and school lessons are stored in DNA or RNA (capable of storing only low-level chemical information).  Human DNA has been extremely well-studied by long well-funded multi-year research projects such as the Human Genome Project completed in 2003 and the ENCODE project, and no one has found a bit of evidence of anything in DNA that stores episodic memory or any information learned in school.

Tee and Taylor then give us more examples of experiments that they think may support the idea of memories stored in the bodies of neurons (rather than synapses). But they fail to actually support such an idea because the studies follow Questionable Research Practices.  For example, they cite the study here, which fails to qualify as a robust well-designed study because it uses study group sizes as small as 9, 11 and 13. To give another example, Tee and Taylor cite the Glanzman study here, which  fails to qualify as a robust well-designed study because it uses study group sizes as small as 7. Alas, the use of insufficient sample sizes is the rule rather than the exception in today's cognitive neuroscience, and Tee and Taylor seem to ignore this problem.  

The heavily hyped Glanzman study (guilty of Questionable Research Practices) claimed a memory transfer between aplasia animals achieved by RNA injections. Such a study can have little relevance to permanent memory storage, because RNA molecules have very short lifetimes of less than an hour. 

Finally in Tee and Taylor's paper, we have a Conclusions section, which begins with this confession which should cause us to doubt all claims of neural memory storage: "After more than 70 years of research efforts by cognitive psychologists and neuroscientists, the question of where memory information is stored in the brain remains unresolved."  This is followed by a statement that is at least true in the first part: "Although the long-held synaptic hypothesis remains as the de facto and most widely accepted dogma, there is growing evidence in support of the cell-intrinsic hypothesis."  It is correct to call the synaptic memory hypothesis a dogma (as I have done repeatedly on this blog). But Tee and Taylor commit an error in claiming "there is growing evidence in support of the cell-intrinsic hypothesis" (the hypothesis that memories are stored in the bodies of neurons rather than synapses that are part of connections between neurons).  There is no robust evidence in support of such a hypothesis, and the papers Tee and Taylor have cited as supporting such a hypothesis are unconvincing because of their Questionable Research Practices such as too-small sample sizes. 

On their last two page the authors end up in shoulder-shrugging mode, saying, "while the cell might be storing the memory information, the synapse might be required for the initial formation and the subsequent retrieval of the memory."  We are left with the impression of scientists in disarray, without any clear idea of what they are talking about, rather like some theologian speculating about exactly where the angels live in heaven, bouncing around from one idea to another.  In their last paragraph Tee and Taylor speculate about memories being inherited from one generation to another by DNA, which is obviously the wildest speculation. 

Our takeaway from Tee and Taylor's recent paper should be this: scientists are in baffled disarray on the topic of memory. They have no well-established theory of memory storage in the brain, and are waffling around between different speculations that contradict each other.  We are left with strong reasons for suspecting that scientists are getting nowhere trying to establish a theory of memory storage in the brain.  This is pretty much what we should expect if memories are not stored in brains, and cannot be stored in brains.  Always be very suspicious when someone says something along the lines of, "What scientists have been teaching for decades is not true, but they have a new theory that has finally got it right." More likely the new theory is as false as the old theory. 

If anyone is tempted to put credence in this "cell-intrinsic hypothesis" of memory storage, he should remind himself of the physical limitations of DNA.  DNA uses what is called the genetic code. The genetic code is shown below. The A, C, T and G letters at the center stand for the four types of nucleotide base pairs used by DNA:  adenine (A), cytosine (C), guanine (G), and thymine (T). Different triple combinations of these base pairs stand for different amino acids (the twenty types of chemicals shown on the outer ring of the visual below). 

So DNA is profoundly limited in what it can store. In the human body DNA can only store low-level chemical information. We know of no way in which DNA in a human body could store any such things as information learned in school or episodic memories.  Such things cannot be stored using the genetic code used by DNA.  No one has ever found any evidence that strings of characters (such as memorized text) are stored in human DNA, nor has anyone found any evidence that visual information is stored in human DNA. Moreover, if we had to write memories to DNA or read memories from DNA, it would be all-the-more impossible to explain the phenomena of instant memory formation and instant memory retrieval. 

Some have suggested that DNA methylation marks might be some mechanism for memory storage. This idea is very unbelievable. DNA methylation is the appearance of a chemical mark on different positions of DNA.  The chemical mark is almost always the same H₃C addition to the cytosine nucleotide base pair.  These chemical marks serve as transcription suppressors which prevent particular genes from being expressed. Conceptually we may think of a DNA methylation mark as an "off switch" that turns off particular genes. 

The idea that the collection of these chemical "off switches" can serve as a system for storing memories is unbelievable. DNA is slowly read by cells in a rather sluggish process called transcription, but there is no physical mechanism in the body for specifically reading only DNA methylation marks. If there were anything in the body for reading only DNA methylation marks, it would be so slow that it could never account for instant memory recall.  We know the purpose that DNA methylation marks serve in the body: the purpose of switching off the expression of particular genes. Anyone claiming that such marks also store human memories is rather like some person claiming that his laundry detergent is a secret system for storing very complex information. 

A metric relevant to such claims is the maximum speed of DNA transcription. The reading of DNA base pairs occurs at a maximum  rate of about 20 amino acids per second, which is about 60 nucleotide pairs per second.  This is the fastest rate, with preparatory work being much slower. DNA methylation occurs only for one of the four base pairs, meaning that no more than about 15 DNA methylation marks could be read in a second (after slower preparatory work is done).  

Let us imagine (very implausibly) that DNA methylation marks serve as a kind of binary code for storing information.  Let us also imagine (very implausibly) that there is a system by which letters can be stored in the body, by means of something like the ASCII code, and by means of DNA methylation.  Such a system would have storage requirements something like this:

Letter	ASCII number equivalent	Binary equivalent
A	12	1100
B	13	1101
C	14	1110

Under such a storage system, once the exact the spot had been found for reading the right information (which would take a very long time given that the brain has no indexing system and no position coordinate system), and after some chemical preparatory work had been done to enable reading from DNA, information could be read at a rate of no more than about four characters per second. But humans can recall things  much faster than such a rate. When humans talk fast, they are speaking at a rate of more than two words per second (more than 10 characters per second).  So if you ask me to describe how the American Civil War began and started and ended, I can spit out remembered information at a rate several times faster than we can account for by a reading of DNA methylation marks, even if we completely ignore the time it would take to find the right little spot in the brain that stored exactly the right information to be recalled. 

A realistic accounting of the time needed for memory recall of information stored in binary form by DNA methylation would have to add up all of these things:

• The time needed for finding the exact spot in the brain where the correct recalled information was stored (requiring many minutes or hours or days, given no indexing and no coordinate system in the brain);
• The time needed for chemical preparatory work that would have to be done before DNA can be read (such as the time needed to get RNA molecules that can do the reading);
• Reading DNA methylation marks (encoding binary numbers) at a maximum rate of no more than four characters per second (and usually a much slower rate because of a sparse scattering of such marks);
• Translating such binary numbers into their decimal equivalent;
• Translating such decimal numbers into character equivalents;
• Translating such retrieved letters into speech.

All of this would be so slow that if memories were stored as DNA methylation marks, you would never be able to speak correct recalled information at a rate a tenth as fast as two words per second, as humans can do. Similarly, you would never be able to form new memories instantly (as humans are constantly doing) if memory storage required writing binary information as DNA methylation marks, which would be a very slow process.  Humans can form new memories at the same rate at which they can recall memories. Suppose you are leaving to go food shopping and someone in your house says, "Please buy me a loaf of whole wheat bread and some orange juice." You may form a new memory of those exact words, at a rate of two words per second.  Storing such information as DNA methylation marks would be much slower than such a rate. 

I may note that while scientists can read DNA and DNA methylation marks from neural tissue, no one has ever found the slightest speck of human learned information stored in DNA or DNA methylation marks, synapse strengths, or any other type of representation in the brain; nor has anyone found any evidence of any coding scheme by which letters or numbers or visual images are stored in human DNA or DNA methylation marks.  When brain surgeons remove half of a brain (to treat very severe seizures) or remove portions of a brain (to treat severe epilepsy or cancer), they discard the cut-out brain tissue, and do not try to retrieve memory information stored in it.  They know that attempting such a thing would be utterly futile. 

It has been claimed by the few proponents of memory stored in the DNA methylation marks that such marks are a stable medium for writing information. But search for "DNA methylation turnover" and you will find contrary claims, such as a paper entitled "Rapid turnover of DNA methylation in human cells." 

NIH Bets $1,434,188 That Synapses Don't Store Memories

In today's news we read a press release from the National Institute of Health entitled "NIH supports 106 grants featuring high-risk, high-reward research."  The research discussed are projects with a high risk of failure, but which might yield a high reward if they succeed.  We read the following: "Supported research this year includes understanding how long-term memory might be encoded in the shape of folded DNA in our neurons, mining data from unconventional sources to reveal social determinants of suicide, establishing new paradigms to address the functional consequences of health disparities in drug development, and looking at the impact of high school and collegiate athlete injuries on long-term health." 

The first project mentioned (apparently NIH Project # 1DP2MH129985-01 discussed on this page) is relevant to the question of whether scientists currently have any credible theory of the storage of long-term human memories.  For many decades scientists have been telling us that long-term memories are stored in synapses.  There has never been any robust evidence or any credible detailed theory backing up such an idea.  Everything we know about synapses suggests that they are totally unsuitable for the task of storing memories that can last for 50 years. For example, the proteins in synapses have average lifetimes of only a few weeks or less. Synapses have a high degree of structural dependency on dendritic spines, which are short-lived things that do not last for years.  No one has ever proven that a synapse lasts for years, and we have good reason for believing they do not last for years. 

What is interesting about this NIH Project # 1DP2MH129985-01 is that it is a kind of "heresy" project that is totally contrary to the "orthodoxy" that our neuroscientists have been spouting for decades about memory.  The project has the wildly speculative title "The epigenetic encoding of learning and memory," which is a research project title as speculative as "Extraterrestrial UFO mother-ships near Jupiter."  The idea that human memories are encoded in the genome or the epigenome is an idea totally contrary to what neuroscientists have been telling us for decades, that memories are stored in synapses.  The genome and the epigenome are found in the center of cells. A synapse is a unit vastly tinier than a cell, outside of a cell or or on the outer edge of a cell.  In the visual below depicting a neuron (one of the cells in the brain), the brown circle at the center is the location of the genome and the epigenome, and synapses (too small to show) would be located around the orange parts on the edges:

We see from the project page that the NIH has granted $1,434,188 of public funds for this new project. The project page presents no detailed research project plan. We merely get a vague project description that leaves the researchers free to play around pretty much in any way they want.  That description often resorts to speculation stated as if it were fact. Here is the description (I'll put in boldface the very speculative parts that are not at all statements of fact):

"The nervous system requires tight control of transcription for processes such as learning and memory formation. The field of epigenetics seeks to understand how changes to gene transcription occur in response to environmental cues and external signals such as those that our brains experience during learning. This proposal lies at the intersection of neuroscience and epigenetics, with a particular focus on chromatin biology. Chromatin is the complex of DNA and the histone proteins that wrap up DNA into complex structures, recruit key transcriptional regulators, and in doing so, control gene expression. In recent years, it has become clear that disruptions to chromatin regulation lead to a range of neurological and mental health disorders such as post- traumatic stress disorder (PTSD). However, we have a limited understanding of how chromatin functions in the brain or how its disruption can lead to disease. We will apply the tools and techniques of the epigenetics field to the study of neuronal function. In doing so, we hope to elucidate the molecular mechanisms that allow our brains to perform incredibly complex tasks and how disruption of these mechanisms can lead to neuronal dysfunction. We propose overcome long-standing hurdles in the field using a combination of novel techniques to reveal how the epigenetic landscape encodes the transcriptional changes that underlie memory formation. Specifically, we seek to uncover the transcriptional signature of memory formation and memory maintenance within single neurons in an in vivo context. We then will examine the epigenetic underpinnings of this transcriptional signature and manipulate specific components of the chromatin environment to define their contribution to learning and memory maintenance. First, in order to elucidate the gene program associated with learning, we will use single-nucleus RNA-sequencing in combination with mouse models that label the specific neurons activated during learning. This will allow us to examine the transcriptional programs activated in neurons that form a memory engram compared to their neighboring cells at various times after learning. Next, we will employ a quantitative biochemical approach uniquely available to our group as part of the Epigenetics Institute to characterize the chromatin landscape changes the occur during memory formation, memory maintenance, and reversal learning. Finally, we will modify the chromatin landscape by manipulating specific histone proteins in combination with numerous sequencing approaches to elucidate how chromatin controls learning and the transcriptional program. Employing this novel combination of techniques will allow us to uncover the mechanisms through which the epigenome encodes information within neurons to modify behavior both in the context of normal learning and in the context of maladaptive responses that lead to disorders such as PTSD. If successful, these methods will 1) identify the transcriptional signature that encodes a memory in neurons, 2) map how this signature is encoded by specific epigenetic regulatory mechanisms, and 3) define how the chromatin landscape affects memory formation and contributes to mental health disorders."

What we have here (in the boldface parts) are statements of an unfounded and wildly speculative theory: the contrarian idea that memories are stored in chromatin (consisting of DNA and proteins surrounding it) and an  associated epigenome (consisting of kind of chemical marks next to parts of DNA) . Such statements are made in a matter-of-fact manner, as if such a "yet-to-reach-first-base" theory was fact.  The not-yet-popular theory being suggested is one very different from what neuroscientists have been claiming for decades.  For decades, neuroscientists have been telling us that memory formation occurs through "synapse strengthening," not through "transcriptional changes."  We see no mention of the word "synapses" or "synaptic" in the quotation above. 

The boldface above states an idea that makes no sense. "Transcriptional signatures" are transitory fleeting fluctuating biomarkers of the rates at which particular genes are being expressed. Conversely, for a long-term memory to be encoded in a brain there would need to be some all-but-miraculous effect that caused learned information or sensory experience to be permanently stored as brain states or synapse states, rather like letters being written into clay.  Referring to "the transcriptional signature that encodes a memory in neurons" is rather like saying the words from your lips are a tape  recorder that permanently store what you are saying. But since "transcriptional signatures" bear no resemblance to sensory experience, it's far worse, and would be more like making the double-goofy claim that your heart rate fluctuations are a tape recorder that record all the words you speak. 

We should be extremely suspicious and skeptical whenever scientists suddenly start giving some new answer to a fundamental question,  an answer completely different from the answer they have been dogmatically declaring for years. For example, if scientists were to suddenly start telling us that galaxies are not held together by gravity (as they've been telling us for decades), but by, say, “dark energy pulsations,” we should be extremely skeptical that the new explanation is correct. In this case, there are very good reasons why the speculations in boldface above cannot be right.

Chromatin is a term meaning DNA and surrounding histone protein molecules. Histone molecules are not suitable for storing very long-term memories because they are too short-lived. A scientific paper tells us that the half-life of histones in the brain is only about 223 days, meaning that every 223 days half of the histone molecules will be replaced.

So histone molecules are not a stable platform for storing very long-term memories that can last for 50 years. But what about DNA? The DNA molecule is stable. But there are several reasons why your DNA molecules cannot be storing your memories. The first reason is that your DNA molecules are already used for another purpose – the storing of genetic information used in making proteins. DNA molecules are like a book that already has its pages printed, not a book with empty pages that you can fill. The second reason is that DNA molecules use a bare bones “amino acid” language quite unsuitable for writing all the different types of human memories. The idea that somewhere your DNA has memory of your childhood summer vacations (expressed in an amino-acid language) is laughable.

The third reason is that the DNA of humans has been exhaustively analyzed by various multi-year projects such as the Human Genome Project and the ENCODE project, as well as various companies that specialize in personal analysis of the DNA of individual humans. Despite all of this huge investigation and analysis, no one has found any trace whatsoever of any type of real human memory (long-term or short-term) being stored in DNA. If you do a Google search for “can DNA store memories,” you will see various articles (most of them loosely-worded, speculative and exaggerating) that discuss various genetic effects (such as gene expression) that are not the same as an actual storage of a human memory. Such articles are typically written by people using the word “memories” in a very loose sense, not actually referring to memories in the precise sense of a recollection.

The fourth reason is that there is no known bodily mechanism by which lots of new learned information can be quickly written to the storage area inside a DNA molecule. The fifth reason is that the DNA we see in brain neurons is basically identical to the DNA we see in other parts of the body (such as the DNA from foot cells). If memories were stored in DNA, the DNA in brain neurons would be much different from that of the DNA in other body parts.  We can read DNA (including an epigenome) from dead bodies, and no one has ever found a memory in a dead body. 

It takes about 1 minute for a cell to read only the small part of the DNA needed to make a single protein (and DNA has recipes for thousands of proteins). If your memories were stored in DNA, it would take you hours to remember things that you can actually recall instantly. Thinking that DNA can store your memories is like thinking that your refrigerator can print out your resume. 

The epigenome consists of chemical "marks" on particular parts of DNA that can act to turn off or turn on particular genes. We already know the function of such chemicals (a function different from memory), and no one has any credible theory of how such chemicals could possibly fulfill such a function and also do the infinitely more complex task of storing a memory (which would be something like a functional broom that also lets you fly around like a witch).  Reading and writing such chemical "marks" is a very slow affair, meaning the epigenome can't be the explanation for realities such as the instant recall of a memory or the instant formation of a new permanent memory. 

But couldn't very-long term memories just be stored in some unknown part of a neuron? No, because the proteins that make up neurons have short lifetimes. A scientist explains the timescales:

"Protein half-lives in the cell range from about 2 minutes to about 20 hours, and half-lives of proteins typically are in the 2- to 4-hour time range. Okay, you say, that's fine for proteins, but what about 'stable' things like the plasma membrane and the cytoskeleton? Neuronal membrane phospholipids turn over with half-lives in the minutes-to-hours range as well. The vast majority of actin microfilaments in dendritic spines of hippocampal pyramidal neurons turn over with astonishing rapidity—the average turnover time for an actin microfilament in a dendritic spine is 44 seconds...As a first approximation, the entirety of the functional components of your whole CNS [central nervous system] have been broken down and resynthesized over a 2-month time span. This should scare you. Your apparent stability as an individual is a perceptual illusion."

There is no credible theory of human learned memories could be stored and retrieved by brains. The low-level facts we have learned about the brain reveal it to be an organ with enormous signal noise, unreliable synaptic transmission, billions of synaptic-gap signal slowers, and very high molecular turnover, an organ bearing no resemblance to a system for permanently storing and instantly retrieving memories with high information accuracy.  The fact that the NIH is now betting $1,434,188 on some new theory of neural memory completely different from the memory storage doctrine neuroscientists have been teaching for decades is something that should lead us to suspect cognitive neuroscientists are in disarray, and very much lacking in credibility in their statements about brains and memory.  Similarly, you should have little confidence in some  astronomer if he told you (after twenty years of telling you that star shine is caused by nuclear fusion) that now he has a totally different theory of what causes starlight.

Postscript: The National Science Foundation's query tool shows that $600,000 has been allocated for another bet that synapses don't store memories. That is the amount of money allocated to the project described on this page:

https://www.nsf.gov/awardsearch/showAward?AWD_ID=2050850&HistoricalAwards=false

The project (NSF award # 2050850) is one entitled "Elucidation of RNA-Based Mechanisms of Long-Term Memory Storage." The idea of an RNA-based mechanism of long-term memory storage is an absurd one. RNA is a short-lived molecule. Referring to David Glanzman, the project incorrectly states, " the principal investigator has discovered that long-term memory (LTM) in the marine snail Aplysia appears to be stored in neurons by nuclear changes." No such thing has been discovered by Glanzman or anyone else. Glanzman's paper here received lots of press incorrectly talking about a "memory transfer" between marine snails.  The paper provided no robust evidence for any such thing, and involved study group sizes of only 7, way too small for a reliable result. 

As for NIH Project # 1DP2MH129985-01 discussed on this page, the project has had two years of funding, but it has not produced any papers backing up the idea of memory storage in the epigenome. A search for David Glanzman's recent papers on Google scholar shows that the NSF award # 2050850 has failed to produce any interesting papers backing up claims of RNA-based mechanisms of long-term memory storage. 

Why We Should Not Think the Human Brain Can Store Very Old Memories

Neurologists like to assume that all your memories are stored in your brain. But there are actually quite a few reasons for doubting this unproven assumption, including the research of scientists such as Karl Lashley and John Lorber. Their research showed that minds can be astonishing functional even when large parts of the brain are destroyed, either through disease or deliberate surgical removal. Lorber documented 600 cases of people with heavy brain damage (mostly due to hydraencephaly), and found that half of them had above average intelligence. Some children with brain problems sometimes undergo an operation called a hemispherectomy, in which half of their brain is removed. An article in Scientific American tells us, “Unbelievably, the surgery has no apparent effect on personality or memory.”

Given such very astonishing anomalies, we should give serious consideration to all arguments against the claim that your brain is storing all your memories. I will now discuss such an argument. The argument can be summarized as follows: there is no plausible mechanism by which the human brain could store very long-term memories such as 50-year-old memories. Every neurological memory theory that we have cannot explain any memories that have persisted for more than a year.

The Fact That Humans Can Remember Things for 50 Years

First, let's look at the basic fact of extreme long-term memory storage. It is a fact that humans can recall memories from 50 years ago. Some people have tried to suggest that perhaps human memory doesn't work for such a long time, and that remembering very old memories can be explained by the idea of what is called “rehearsal.” The idea is that perhaps a 60-year-old remembering is really just remembering previous recollections that he had at an earlier age. So perhaps, this idea goes, when you are 60 you are just remembering what you remembered from your childhood at 50, and that at 50 you were just remembered what you remembered from your childhood at age 40, and so forth.

But such an idea has been disproved by experiments. A scientific study by Harry Bahrick was entitled “Semantic memory content in permastore: Fifty years of memory for Spanish learned in school.” It showed that “large portions of the originally acquired information remain accessible for over 50 years in spite of the fact the information is not used or rehearsed.” The same researcher tested a large number of subjects to find out how well they could recall the faces of high school classmates, and found very substantial recall even with a group that had graduated 47 years ago. Bahrick reported the following:

Subjects are able to identify about 90% of the names and faces of the names of their classes at graduation. The visual information is retained virtually unimpaired for at least 35 years...Free-recall probability does not diminish over 50 yr for names of classmates assigned to one or more of the Relationship Categories A through F.

I know for a fact that memories can persist for 50 years, without rehearsal. Recently I was trying to recall all kinds of details from my childhood, and recalled the names of persons I hadn't thought about for decades, as well as a Christmas incident I hadn't thought of for 50 years (I confirmed my recollection by asking my older brother about it). Digging through my memories, I was able to recall the colors (gold and purple) of a gym uniform I wore, something I haven't thought about (nor seen in a photograph) for some 47 years. Upon looking through a list of old children shows from the 1960's, I saw the title “Lippy the Lion and Hardy Har Har,” which ran from 1962 to 1963 (and was not syndicated in repeats, to the best of my knowledge). I then immediately sung part of the melody of the very catchy theme song, which I hadn't heard in 53 years. I then looked up a clip on a youtube.com, and verified that my recall was exactly correct. I also recently recalled "The Patty Duke Show" from the 1960's, a show I haven't seen in 50 years, and recalled that in the opening title sequence we saw Patty walking down some stairs. I looked up the title sequence on www.youtube.com, and verified that my 50-year-old memory was correct. This proves that a 53-year-old memory can be instantly recalled.

So in trying to explain human memory, we need to have a theory that can explain human memories that persist for 50 years. Very confusingly, scientists use the term “long-term memory” for any memory lasting longer than an hour, which is very unfortunate because almost every thing you will find on the internet (seaching for “long term memory”) does not actually explain very long-term memory such as memories lasting for 50 years.

Why LTP and Synapse Plasticity Cannot Explain Very Long-Term Memory

Now let's look at neuroscientists' theories of memories. Quora.com is a “expert answer” website which claims to give “the best answer to any question.” One of its web pages asks the question, “How are memories stored and retrieved in the human brain?” The top answer (the one with most upvotes) is by Paul King, a computational neuroscientist. King very dogmatically gives us the following answer:

At the most basic level, memories are stored as microscopic chemical changes at the connection points between neurons in the brain..As information flows through the neural circuits and networks of the brain, the activity of the neurons causes the connection points to become stronger or weaker in response. The strengthening and weakening of the synapses (synaptic plasticity) is how the brain stores information. This mechanism behind this is called "long-term potentiation" or "LTP."

But there is actually no proof that any information is being stored when synapses are strengthened. From the mere fact that synapses may be strengthened when learning occurs, we are not entitled to deduce that information is being stored in synapses, for we also see blood vessels in the leg strengthen after repeated exercise, and that does not involve information storage. In order to actually prove that a synapse is storing information, you would need to do an experiment such as having one scientist store a symbol in an animal's brain (by training), and then have another scientist (unaware of what symbol had been stored) read that symbol from some synapses in the animal's brain, correctly identifying the symbol. No such experiment has ever been done.

The idea that a memory forms after repeating strengthening of synapses is inconsistent with the fact people very commonly remember things they experienced only one time. Almost every time someone tells you about a TV show they saw last night, or a conversation they recently had with a friend, they are remembering something they only were saw or heard one time, not through repeated experiences.

The evidence does not even clearly indicate that LTP correlates with memory, as one scientist's summary of experimental results indicates (a summary utterly inconsistent with the claim LTP is a general mechanism to explain memory).

What this means is that LTP and memory have been dissociated from each other in almost every conceivable fashion. LTP can be decreased and memory enhanced. Hippocampus-dependent memory deficits can occur with no discernable effect on LTP...There will be no direct quantitative or even qualitative relationship between LTP measured experimentally and memory measured experimentally—that is already abundantly clear from the available literature...The most damning observations probably are those examples where LTP is completely lost and there is no effect on hippocampus-dependent memory formation.

A scientific paper states this about LTP:

Based on the data reviewed here, it does not appear that the induction of LTP is a necessary or sufficient condition for the storage of new memories.

LTP is so weak an effect it is hard to even detect it. A scientific paper asks the following:

Why is it so difficult to see learning-associated synaptic changes?And does their absence in numerous experiments favor the null hypothesis?

What is misleadingly called “long-term potentiation” or LTP is a not-very-long-lasting effect by which certain types of high-frequency stimulation (such as stimulation by electrodes) produces an increase in synaptic strength. 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.

Since then a few studies have claimed to find evidence that LTP occurred during learning. But there is actually an insuperable problem in the idea that long-term potentiation could explain very long-term memories. The problem is that 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 the following:

Potentiation almost always decays to baseline levels within a week. These results suggest that while LTP is long-lasting, it does not correspond to the time course of a typical long-term memory. It is recognized that many memories do not last a life-time, but taking this point into consideration, we would then have to propose that LTP is only involved in the storage of short-term to intermediate memories. Again, we would be at a loss for a brain mechanism for the storage of a long-term memory.

A more recent scientific paper (published in 2013) 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.” 

Another 2013 paper agrees that so-called long-term potentiation is really very short-lived:

LTP always decays and usually does so rapidly. Its rate of decay is measured in hours or days (for review, see Abraham 2003). Even with extended “training,” a decay to baseline levels is observed within days to a week.

Scientists distinguish between two types of LTP: an E-LTP that can be produced by a single electrical stimulus, but only lasts one to three hours, and an L-LTP that requires multiple electrical stimulations, and can last about 8 hours or a little longer. But this fails to correspond to what we know about human memory, which is that humans can form a memory lasting decades after a single sensory experience. 

So evidently long-term potentiation cannot be any foundation or mechanism for long-term memories. This is the conclusion reached by the previous paper when it makes this conclusion about long-term potentiation (LTP):

In summary, if synaptic LTP is the mechanism of associative learning—and more generally, of memory—then it is disappointing that its properties explain neither the basic properties of associative learning nor the essential property of a memory mechanism. This dual failure contrasts instructively with the success of the hypothesis that DNA is the physical realization of the gene.

The book "Neuronal Mechanisms of Memory Formation" hints on page 451 that LTP may be a poor candidate for such a thing. It says this:

Definitive empirical support for synaptic plasticity modeled by LTP being a mechanism of memory processing is still lacking. For each piece of evidence that lends some support to the theory, there is likely to be equally strong evidence to suggest the contrary. The field of research reached a veritable stalemate some years ago when so-called cornerstones of research that supported the hypothesis were unable to be replicated...and the outcome was an increasing skepticism about whether LTP can be considered a neural substrate for learning and memory.

Referring to this scientific paper, another paper suggests that "LTP as a memory mechanism" may be more of a dogma than something well established by observations:

Shors and Matzel,,.concluded that LTP did not meet the criteria for providing a causal mechanism of memory. To make a long argument very short, they documented instances where changes in memory occur without LTP and where LTP occurs without changes in memory.....They report that between 1974 and 1997, more than 1300 articles occurred with “LTP” in the title. Of these, fewer than 80 described any behavioral manipulation relevant to assessing changes in memory. Furthermore, the articles that contained behavioral manipulations tended to provide evidence against the hypothesis that LTP is a memory mechanism. Thus, the claim that LTP is a molecular mechanism for learning and memory may be more of a dogma of neuroscientific memory research than a hypothesis that is being rigorously tested.  

A 2014 book stated, "Although LTP is considered to be the primary model for how learning and memory storage occur at the synapse level, the evidence supporting this claim is still inconclusive and speculative." A 1995 scientific paper found. "There is a striking negative correlation of spatial learning ability with LTP." This is the exact opposite of what we should expect if LTP was some type of memory mechanism. 

But what about syntaptic plasticity, previously mentioned in my quote from the neurologist King ? Since he claimed that LTP is the mechanism behind synaptic plasticity, and LTP cannot explain any memory lasting longer than a year, then synaptic plasticity will not work to explain very long-term memories.

To study LTP, scientists typically perform something artificial called tetanic stimulation, using a frequency of 100 hertz. A normal brain does not transmit signals at a frequency so high. Of the common brain waves (alpha, beta, and gamma), only gamma waves have a frequency of greater than 30 hertz, and such gamma waves generally do not have a frequency higher than 50 hertz.  LTP can be induced using a lower frequency, but only by prolonged stimulation such as stimulation lasting minutes. That type of sluggish low-frequency stimulation cannot explain human memories that can form instantly. 

Why Synapses Cannot Explain Very Long-Term Memory

Long-term memory cannot be stored in synapses, because synapses don't last long enough. Below is a quote from a scientific paper:

A quantitative value has been attached to the synaptic turnover rate by Stettler et al (2006), who examined the appearance and disappearance of axonal boutons in the intact visual cortex in monkeys.. and found the turnover rate to be 7% per week which would give the average synapse a lifetime of a little over 3 months.

You can read Stettler's paper here. A 2019 paper documents a 16-day examination of synapses, finding "the dataset contained n = 320 stable synapses, n = 163 eliminated synapses and n = 134 formed synapses."  That's about a 33% disappearance rate over a course of 16 days, suggesting an average synapse lifetime of less than three months.

You can google for “synaptic turnover rate” for more information. We cannot believe that synapses can store-long memories for 50 years if synapses only have an average lifetime of about 3 months. The paper here says the half-life of synapses is "from days to months."

Synapses often protrude out of bump-like structures on dendrites called dendritic spines. But those spines have lifetimes of less than 2 years.  Dendritic spines last no more than about a month in the hippocampus, and less than two years in the cortex. This study found that dendritic spines in the hippocampus last for only about 30 days. This study found that dendritic spines in the hippocampus have a turnover of about 40% each 4 days. This 2002 study found that a subgroup of dendritic spines in the cortex of mice brains (the more long-lasting subgroup) have a half-life of only 120 days. A paper on dendritic spines in the neocortex says, "Spines that appear and persist are rare." While a 2009 paper tried to insinuate a link between dendritic spines and memory, its data showed how unstable dendritic spines are.  Speaking of dendritic spines in the cortex, the paper found that "most daily formed spines have an average lifetime of ~1.5 days and a small fraction have an average lifetime of ~1–2 months," and told us that the fraction of dendritic spines lasting for more than a year was less than 1 percent. A 2018 paper has a graph showing a 5-day "survival fraction" of only about 30% for dendritic spines in the cortex.  A 2014 paper found that only 3% of new spines in the cortex persist for more than 22 days. Speaking of dendritic spines, a 2007 paper says, "Most spines that appear in adult animals are transient, and the addition of stable spines and synapses is rare." A 2016 paper found a dendritic spine turnover rate in the neocortex of 4% every 2 days. A 2018 paper found only about 30% of new and existing dendritic spines in the cortex remaining after 16 days (Figure 4 in the paper). 

Furthermore, it is known that the proteins existing between the two knobs of the synapse (the very proteins involved in synapse strengthening) are very short-lived, having average lifetimes of no more than a few days. A graduate student studying memory states it like this:

It’s long been thought that memories are maintained by the strengthening of synapses, but we know that the proteins involved in that strengthening are very unstable. They turn over on the scale of hours to, at most, a few days.

A scientific paper states the same thing:

Experience-dependent behavioral memories can last a lifetime, whereas even a long-lived protein or mRNA molecule has a half-life of around 24 hrs. Thus, the constituent molecules that subserve the maintenance of a memory will have completely turned over, i.e. have been broken down and resynthesized, over the course of about 1 week.

The paper cited above also states this (page 6):

The mutually opposing effects of LTP and LTD further add to the eventual disappearance of the memory maintained in the form of synaptic strengths. Successive events of LTP and LTD, occurring in diverse and unrelated contexts, counteract and overwrite each other and will, as time goes by, tend to obliterate old patterns of synaptic weights, covering them with layers of new ones. Once again, we are led to the conclusion that the pattern of synaptic strengths cannot be relied upon to preserve, for instance, childhood memories.

The latest and greatest research on the lifetime of synapse proteins is the June 2018 paper “Local and global influences on protein turnover in neurons and glia.” The paper starts out by noting that one earlier 2010 study found that the average half-life of brain proteins was about 9 days, and that a 2013 study found that the average half-life of brain proteins was about 5 days. The study then notes in Figure 3 that the average half-life of a synapse protein is only about 5 days, and that all of the main types of brain proteins (such as nucleus, mitochondrion, etc.) have half-lives of 15 days or less.  The 2018 study here precisely measured the lifetimes of more than 3000 brain proteins from all over the brain, and found not a single one with a lifetime of more than 75 days (figure 2 shows the average protein lifetime was only 11 days). 

The paper here states, "Experiments indicate in absence of activity average life times ranging from minutes for immature synapses to two months for mature ones with large weights."

When you think about synapses, visualize the edge of a seashore. Just as writing in the sand is a completely unstable way to store information, long-term information cannot be held in synapses. The proteins in between the synapses are turning over very rapidly (lasting no longer than about a week), and the entire synapse is replaced every few months.

In November 2014 UCLA professor David Glanzman and his colleagues published a scientific paper publishing research results. The authors said, “These results challenge the idea that stable synapses store long-term memories." Scientific American published an article on this research, an article entitled, “Memories May Not Live in Neuron's Synapses.” Glanzman stated, “Long-term memory is not stored at the synapse,” thereby contradicting decades of statements by neuroscientists who have dogmatically made unwarranted claims that long-term memory is stored in synapses.

Why Very Long-Term Memories Cannot Be Stored in the Cell Nucleus

His research has led Glanzman to a radical new idea: that memories are not stored in synapses, but in the nerve cell nucleus. In fact, in this TED talk Glanzman dogmatically declares this doctrine. At 15:34 in the talk, Glanzman says, “memories are stored in the cell nucleus – it is stored as changes in chromatin.” This is not at all what neurologists have been telling us for the past 20 years, and few other neuroscientists have supported such an idea.

We should be extremely suspicious and skeptical whenever scientists suddenly start giving some new answer to a fundamental answer, an answer completely different from the answer they have been dogmatically declaring for years. For example, if scientists were to suddenly start telling us that galaxies are not hold together by gravity (as they've been telling us for decades), but by, say, “dark energy pulsations,” we should be extremely skeptical that the new explanation is correct. In this case, there are very good reasons why Glanzman's recently-hatched answer to where long-term memories are stored cannot be right.

Chromatin is a term meaning DNA and surrounding histone protein molecules. Histone molecules are not suitable for storing very long-term memories because they are too short-lived. A scientific paper tells us that the half-life of histones in the brain is only about 223 days, meaning that every 223 days half of the histone molecules will be replaced.

So histone molecules are not a stable platform for storing very long-term memories. But what about DNA? The DNA molecule is stable. But there are several reasons why your DNA molecules cannot be storing your memories. The first reason is that your DNA molecules are already used for another purpose – the storing of genetic information used in making proteins. DNA molecules are like a book that already has its pages printed, not a book with empty pages that you can fill. The second reason is that DNA molecules use a bare bones “amino acid” language quite unsuitable for writing all the different types of human memories. The idea that somewhere your DNA has memory of your childhood summer vacations (expressed in an amino-acid language) is laughable.

The third reason is that the DNA of humans has been exhaustively analyzed by various multi-year projects such as the Human Genome Project and the ENCODE project, as well as various companies that specialize in personal analysis of the DNA of individual humans. Despite all of this huge investigation and analysis, no one has found any trace whatsoever of any type of real human memory (long-term or short-term) being stored in DNA. If you do a Google search for “can DNA store memories,” you will see various articles (most of them loosely-worded, speculative and exaggerating) that discuss various genetic effects (such as gene expression) that are not the same as an actual storage of a human memory. Such articles are typically written by people using the word “memories” in a very loose sense, not actually referring to memories in the precise sense of a recollection.

The fourth reason is that there is no known bodily mechanism by which lots of new information can be written to the storage area inside a DNA molecule. The fifth reason is that the DNA we see in brain neurons is basically identical to the DNA we see in other parts of the body (such as the DNA from foot cells). If memories were stored in DNA, the DNA in brain neurons would be much different from that of the DNA in other body parts. 

To completely defeat the idea that your memories may be stored in your DNA, I will merely remind the reader that DNA molecules are not read by brains – they are read by cells. It takes about 1 minute for a cell to read only the small part of the DNA needed to make a single protein (and DNA has recipes for thousands of proteins). If your memories were stored in DNA, it would take you hours to remember things that you can actually recall instantly. Thinking that DNA can store memories is like thinking that your refrigerator can cook a steak.

But couldn't very-long term memories just be stored in some unknown part of a neuron? No, because the proteins that make up neurons have short lifetimes. A scientist explains the timescales:

Protein half-lives in the cell range from about 2 minutes to about 20 hours, and half-lives of proteins typically are in the 2- to 4-hour time range. Okay, you say, that's fine for proteins, but what about "stable" things like the plasma membrane and the cytoskeleton? Neuronal membrane phospholipids turn over with half-lives in the minutes-to-hours range as well. The vast majority of actin microfilaments in dendritic spines of hippocampal pyramidal neurons turn over with astonishing rapidity—the average turnover time for an actin microfilament in a dendritic spine is 44 seconds...As a first approximation, the entirety of the functional components of your whole CNS [central nervous system] have been broken down and resynthesized over a 2-month time span. This should scare you. Your apparent stability as an individual is a perceptual illusion.

It is occasionally speculated that long-term memories might be stored in microtubules in a cell. But such things do not last long enough to be a storage place for memories lasting decades. A scientific paper tells us how short-lived brain microtubules are:

Neurons possess more stable microtubules compared to other cell types (Okabe and Hirokawa, 1988; Seitz-Tutter et al., 1988; Stepanova et al., 2003). These stable microtubules have half-lives of several hours and co-exist with dynamic microtubules with half-lives of several minutes.

Why Long-Term Memories Cannot Be Stored in the DNA Methylome

DNA methylation occurs when a very simple molecule becomes attached to part of a DNA molecule. Such a simple methyl molecule can act like a kind of flag that switches part of a gene on or off. The set of all of these methyl molecules attached to DNA is known as the DNA methylome. It has been suggested by a few that maybe memories are stored in this DNA methylome. 

The DNA methylome seems like a fairly stable thing, and so you don't have the “low stability” problem of very rapid protein molecule turnover that you have with the theory that memories are stored in synapses. But there are several reasons why it is not credible to maintain that human memories are being stored in such a DNA methylome.

The first reason is that we already know the function of this DNA methylome, that it is something other than storing memories. The methyl molecules that make up the methylome serve the purpose of genetic expression, a very different task than storing memories. If you were to maintain that the DNA methylome serves both of these purposes, it would be kind of like the Saturday Night Live comedic sketch that described a product like “Miracle Whip.” It went like this:

Wife: New Shimmer is a floor wax!
Husband: No, New Shimmer is a dessert topping!
Wife: It's a floor wax!
Husband: It's a dessert topping!
Wife: It's a floor wax, I'm telling you!
Husband: It's a dessert topping, you cow!
Spokesman: [ enters quickly ] Hey, hey, hey, calm down, you two. New Shimmer is both a floor wax and a dessert topping!

The second reason for doubting that memories are stored in the DNA methylome is that the DNA methylome couldn't be read with the speed needed for memory recall that is very fast. The DNA methylome consists of methyl molecules scattered across a DNA molecule. All evidence suggests that reading DNA is relatively slow. DNA transcription occurs at a rate of about 40 to 80 nucleotides per second, and there are billions of such nucleotides. But think of how fast people can recall memories. On the TV show Jeopardy we see people recalling very obscure memories in only a few seconds. When someone talks rapidly, he is retrieving language memories (such as the memory of what a particular word means) in a fraction of a second. That couldn't happen so fast if some relatively slow process of reading DNA was being used.

The third reason for doubting that memories are stored in the DNA methylome is that the methylome does not grow in size as learning occurs. As discussed here, the DNA methylome is larger (percentage-wise) in a newborn baby than in either a young adult or an old man.

The fourth reason for doubting that memories are stored in the DNA methylome is that methylation suppression experiments do not affect memory very dramatically. Scientists have ways of suppressing DNA methylation, and they have tested the effects of such suppression on learning and memory.  A scientific paper says that “inhibiting DNA methylation alters olfactory extinction but not acquisition learning.” Another scientific paper says that when DNA methylation was inhibited, “long-term memory strength itself was not affected.” 

A scientific paper states the following:

Prior studies found no effects of zeb, a DNA methylation inhibitor (Zhou et al., 2002), on learning in A. mellifera (Lockett et al., 2010; Biergans et al., 2012). More recently, Biergans et al. (2016), conducted a meta-analysis of multiple honey bee studies with methylation inhibitors (zeb and RG108), but found no strong overall effect of inhibiting DNA methylation on honey bee learning.

These are not the type of very dramatic effects on learning and memory that one would expect from DNA methylation inhibition if memories were being stored in the methylome. Other studies claiming a stronger effect of DNA methylation inhibition are typically unreliable studies using fewer than 15 animals per study group, and in such low-statistical-power studies there is a high chance of a false alarm or false positive.

There are actually two drugs for humans that work mainly by inhibiting DNA methlyation: azacitidine and decitabine.  If DNA methlyation was a mechanism for memory storage, we would expect that the side effect lists for these drugs would make some mention of a possible effect on learning or memory. But these drugs do not produce such a side effect. It has been claimed by the few proponents of memory stored in the DNA methylation marks that such marks are a stable medium for writing information. But search for "DNA methylation turnover" and you will find contrary claims, such as a paper entitled "Rapid turnover of DNA methylation in human cells." 

When It Comes to Explaining Very Long-Term Memory, Our Neuroscientists Are in Disarray

So how can we summarize the current state of scientific thought on how long-term memory is stored? The word that comes to mind is: disarray. In this matter our scientists are flailing about, wobbling this way and that way; but they aren't getting anywhere in terms of presenting a plausible answer as to how very long-term memory can be stored in the brain. Our scientists have done nothing to plausibly solve the permanence problem – the problem that very long-term memories cannot be explained by evoking transient “shifting sands” mechanisms such as LTP which last much less than a year (or in neurons, which are rebuilt every two months due to protein turnover). On this matter our scientists have merely presented explanatory facades – theories that do not hold up to scrutiny, like some movie studio building facade that you can see is a fake when you walk around and look behind it, finding no rooms behind the front.

Another sign of this disarray is a 2013 scientific paper with the title, “"Very long-term memories may be stored in the pattern of holes in the perineuronal net." After basically explaining in its first paragraph why current theories of long-term memories do not work and are not plausible, the author goes on to suggest a wildly imaginative and absurdly ornate speculation that perhaps the brain is a kind of a giant 3D punchcard, storing information like data used to be stored on the old 2D punchcards used by IBM electronic machinery in the 1970's. The author provides no good evidence for this wacky speculation, mainly discussing imaginary experiments that would lend support to it. The very appearance of such a paper is another sign that currently scientists have no good explanation for very long-term memory. I may note that IBM punchcards only worked because they were read by IBM punchcard-reader machines. In order for the brain to work as giant 3D punchcard, we would have to imagine a brain-reader machine that is nowhere to be found in the human body. There has never existed such a thing as a punchcard that can read itself.

This scientific article quotes a neuroscientist speculating about memory storage. The article says:

Neuroscience has also been struggling to find where the brain stores its memories. “They may be ‘hiding’ in high-dimensional cavities,” Markram speculates.

High-dimensional cavities? Cavities are holes, not information storage media. I think the quote bolsters my claim that scientists do not have any plausible explanation of how brains can be storing memories for 50 years. 

Often the modern neuroscientist will engage in pretentious talk which makes it sound as if there is some understanding of how very long-term memory storage can occur. But just occasionally we will get a little candor from our neuroscientists, such as when neuroscientist Sakina Palida admitted in 2015, “Up to this point, we still don’t understand how we maintain memories in our brains for up to our entire lifetimes.”

Concluding Remarks on Long-Term Memory

For the reasons given above, there is no plausible mechanism by which brains such as ours could be storing memories lasting longer than a year. There are only a few possible physical candidates for things that might store very long-term memory in our brain, and as we have seen, none of them are plausible candidates for a storage of very long-term memory.

The fact that our neurologists claim to have theories as to how very long-term memories could be stored does not mean that any such theory is tenable. Imagine if you lived on a planet in which your consciousness and long-term memory was due to a soul, and that the first time scientists dissected a brain, they found that the brain was filled with sawdust. No doubt such scientists would get busy inventing clever theories purporting to explain how sawdust can generate consciousness and long-term memories.

I may note that memories stretching back 50 years are inexplicable not merely from a neurological standpoint but also from a Darwinian standpoint. As I will argue later, from the standpoint of survival of the fittest and natural selection, there is no reason why any primate organism should ever need to remember anything for longer than about a year or two (it would work just fine to just keep remembering last year's memories). I may note that according to an article on wikipedia.com, the average life span in the Bronze Age was only 26 years old. There is no reason why natural selection (prior to the Bronze Age) would have equipped us to remember things for a length of time twice the average life span in the Bronze Age, and it is not plausible that very long-term memories are a recent evolutionary development.

In this post and in other places on this site, when I use the term “memory” I am referring to things such as episodic memories of life events, learned vocabulary, learned facts, and learned visual information that we can recall (such as identifying the name of an object, or recognizing a face). I do not refer to muscular skills such as the skill of how to ride a bike. Such skills are best referred to as “muscular skills” rather than memory.

Postscript: Richard Huganir led a study that was specifically dedicated to trying to find long-lived proteins in synapses. None were found.  The actual scientific paper found no such thing. Quite to the contrary, the paper found the following:

• Studying thousands of brain proteins, the study found that virtually all proteins in brains are very short-lived, with half-lives of less than a week.
  
• Table 2 of the paper gives specific half-life estimates for the most long-lasting brain proteins, and in this table only 10 out of thousands of brain proteins had half-lives of 10 days or longer.
  
• Of the proteins whose half-life is estimated in Table 2, only one of them has a half-life of longer than 30 days, that protein having a half-life of only 32 days.
  
• A graph in the paper indicates that none of the synapse proteins had a half-life of more than 35 days.
  

Below is a graph from the Huganir paper. It shows that the study found that virtually all proteins in synapses are very short-lived.

Below is another graph from the same paper. It shows that the study found that virtually all proteins in synapses are very short-lived.

Judging from these graphs, none of the proteins found had a half-life of longer than 35 days, and only a few had a half-life of more than 14 days.

The scientific paper (like very many scientific papers) had a misleading title that does not match its observations. The title was "Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover." No such proteins were identified. All of the proteins studied had short lifetimes of less than 75 days; and almost all of the proteins studied had lifetimes of less than a week.

Post-postscript: In 2025 I had a recollection which proved the ability of the mind to recall very old memories that have not been recalled in several decades. For some reason I recalled a book I had read about 50 years ago, and never since: the science fiction book "Galaxies Like Grains of Sand" by Brian Aldiss. I remembered some lines from the book. I wrote them down on paper like this:

"The mirror of the past lies shattered. The fragments you hold in your hand."

After I wrote this recollection of something I had not read, thought of or heard quoted in fifty years, I borrowed the book on www.archive.org.  I see that the lines were these (almost exactly as I remembered them)

"The long mirror of the past is shattered...Only a few fragments are left, and these you hold in your hand." 

Post-post-postscript: The 2025 paper here states that  "the synaptic turnover rate is as high as 1% per day in the visual cortex." That is a rate of about 100% replacement every four months. If that is the typical rate at which synapes are replaced, synapses cannot be the storage place of memories lasting decades.  Quoting an even higher rate of synaptic turnover, the paper here states, "A recent imaging study revealed that the synaptic turnover rate in hippocampal CA1 cells is very high, with an estimated lifetime of 1–2 weeks (Attardo et al., 2015)."