Imaging of Dendritic Spines Hint That Brains Are Too Unstable to Store Memories for Decades

Scientists have very fancy equipment for examining brains at very high resolution. But no microscopic examination of a brain has ever proven or even supported the claim that brains store memories.  The most common claim about a brain storage of memories is that memories are stored in synapses. But the paper here confesses, "Very few studies report long-lasting structural changes of synapses induced by behavioral training."

There are two types of ways to examine brain tissue: in vivo or in vitro. An in vitro examination means looking at some tissue that has been removed from an organism, or some tissue in a dead organism. An in vivo examination means examining tissue in a living organism.  When examining human tissue, there are rather severe constrains on what can be seen in vivo. But there are no constraints on in vitro examinations of newly deceased humans, whenever such humans have donated their bodies to medical science.  The brains of quite a few such humans have been minutely examined with the most sophisticated equipment. No one has ever found evidence of a memory stored in a brain. No one has ever read a memory from a dead person. 

There are a number of ways to do in vivo examinations of the brains of living organisms.  One technique is called time-lapse two-photon laser micrsocopy.  Such technology is not good enough to clearly inspect individual synapses, which are very small. But such microscopy is good enough to show what are called dendritic spines. 

A dendritic spine is a tiny protrusion from one of the dendrites of a neuron. The diagram below shows a neuron in the top half of the diagram. Some dendritic spines are shown in the bottom half of the visual. The bottom half of the visual is a closeup of the red-circled part in the top of the diagram. 

An individual neuron in the brain may have about a thousand such dendritic spines. The total number of dendritic spines in the brain has been estimated at 100 trillion, which is about a thousand times greater than the number of neurons in the brain.  The total number of synapses in the brain has also been estimated at 100 trillion. A large fraction of synapses are connected to dendritic spines. So by studying how long dendritic spines last, we can tell a good deal about how long synapses last. 

It has been hoped that some relation could be drawn between learning and the formation of new dendritic spines.  But scientists try to insinuate a connection between LTP and learning, and a paper says that "Sorra and Harris measuring three-dimensional reconstructed spines from serial section EM pictures, could not find any significant effect of LTP on morphological properties of spines."

No doubt the first scientists who examined dendritic spines were hoping to see some nice regularity and order, perhaps something that might be some kind of coding system by which dendritic spines might store information.  But dendritic spines show no such regularity. Unlike positions in a DNA molecule (which must be one of only four nucelotide base pair types), dendritic spines can be any of many sizes, shapes or lengths. A length of dendrite and its spines (like the length shown in the bottom half of the visual above) seem to bear no resemblance to encoded information.  The vast majority of new dendritic spines do not last longer than a few months.  

Some unconvincing science papers have attempted to suggest a link between learning and dendritic spines.  Here's what goes on in a typical paper of this type:

(1) Some rodent will be given some learning, such as fear conditioning. 

(2) Various dendritic spines will be examined.

(3) Some newly formed dendritic spines will be declared to be "experience dependent," because they appeared while the learning took place. 

It is easy to explain why such papers use an illegitimate methodology. There are very many billions of dendritic spines in the brain, and they come and go rapidly and randomly. So anyone with a good enough microscope could find some stretch of dendritic spines that increased during learning, just as you could find some stretch of dendritic spines that decreased during learning. There is never any good basis for claiming that some stretch of dendritic spines increased because of some particular type of learning.  Similarly, looking around outside I could find some row of leaves that grew bigger when I was studying something, but there would be zero reason for thinking that such an increase was caused by my learning. 

Some studies compare two different sets of subjects, one that was exposed to learning, and another that was not exposed to learning. The studies may report that the subjects exposed to learning had a greater growth of dendritic spines. This is not at all good evidence that dendritic spines have anything to do with learning. We would expect that if dozens of experiments compared sets of dendritic spines undergoing random fluctuations, that some of them would report (purely by chance) that in some of those sets there was a greater growth of dendritic spines. Similarly, if 100 experimenters tracked the pimples of young teenagers with acne both during the first three months of the school year and during summer vacation, some of the experimenters might report greater numbers of new pimples growing during the first three months of the school year, even though there is no causal connection between learning and the number of pimples a teenager may have on his or her skin. 

By examining the tiny protrusions that are dendritic spines, scientists can get some idea of how stable or unstable these dendritic spines are.  If such spines are very unstable, it is a great problem for any theory that memories are stored in synapses.  Unstable dendritic spines would suggest that synapses are unstable, and are unlikely to be a place where memories could be stored for decades.  Even without studying dendritic spines, we have the strongest reason for believing in the instability of synapses: the fact that proteins in synapses have average lifetimes of only a few weeks. 

Dendritic spines last no more than a few months 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 study found that dendritic spines in the cortex of mice brains have a half-life of only 120 days. The wikipedia article on dendritic spines says, "Spine number is very variable and spines come and go; in a matter of hours, 10-20% of spines can spontaneously appear or disappear on the pyramidal cells of the cerebral cortex." Referring to in vivo observations of dendritic spines in the mouse hippocampus, the paper here says the authors "measured a spine turnover of ~40% within 4 days."  The 2017 paper here ("Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex") found the following regarding dendritic spines in the cortex of rodents:

"About 80% of synapses were detectable for a day or longer; about 60% belonged to the stable pool imaged for at least 8 days. Even this stable pool was found to turn over, with only, 50% of spines surviving for 30 days or longer. Assuming stochastic behaviour, we estimate that the mean lifetime of the stable pool would be on the order of 120 days."

We have no good evidence that any dendritic spines survive for more than  a few years. There is an often-cited paper from the year 2000 with the title "Stably maintained dendritic spines are associated with lifelong memories." The title is misleading, like the title of so many scientific papers.  The paper actually found that "a tiny fraction of daily formed new spines (~0.2% of the total spines) could persist for 3–5 months." So the paper found that only 1 in 500 dendritic spines persist for as long as 5 months.  The paper resorts to some dubious math to try to hypothesize that some dendritic spines may last for years. 

More recent papers have made even more clear the high turnover rate of dendritic spines, and have made it seem less likely that any dendritic spines survive for more than a few years.  The 2015 paper 

"Impermanence of dendritic spines in live adult CA1 hippocampus" states the following, describing a 100% turnover of dendritic spines within six weeks:

"Mathematical modeling revealed that the data best matched kinetic models with a single population of spines of mean lifetime ~1–2 weeks. This implies ~100% turnover in ~2–3 times this interval, a near full erasure of the synaptic connectivity pattern."

The paper here states, "It has been shown that in the hippocampus in vivo, within a month the rate of spine turnover approaches 100% (Attardo et al., 2015; Pfeiffer et al., 2018)." The 2020 paper here states, "Only a tiny fraction of new spines (0.04% of total spines) survive the first few weeks in synaptic circuits and are stably maintained later in life."  The author here is telling us that only 1 in 2500 dendritic spines survive more than a few weeks.  Given such an assertion, we should be very skeptical about the author's insinuation that some very tiny fraction of such spines "are stably maintained." No one has ever observed a dendritic spine lasting for years, and the observations that have been made of dendritic spines give us every reason to assume that dendritic spines do not ever last for more than a few years. 

The same studies that show such short lifetimes for dendritic spines show that while they exist, dendritic spines very rarely maintain the same size and shape.  During their short lifetimes, dendritic spines tend to change very much in size and shape.  

Human memories can last a lifetime, but synapses and the dendritic spines they attach to are very unstable "shifting sands" types of things. "Unstable dendritic spines" implies "unstable synapses," which implies that scientists must be wrong when they claim that memories are stored in synapses.  Stable human memories can last for 50 years, so we cannot believe they are stored in things as unstable as synapses and dendritic spines. Studies on the lifetime of the proteins that make up synapses and dendritic spines tell us that such proteins last only a few weeks.  Synapses and dendritic spines are as unstable as fallen maple leaves.  The brain has no place that it could be storing memories that last for decades.

Postscript: The failure of neuroscientists to listen to what dendritic spines are telling us is epitomized by a 2015 review article on denditic spines, which states, "It is also known that thick spines may persist for a months [sic], while thin spines are very transient, which indicate that perhaps thick spines are more responsible for development and maintenance of long-term memory."  It is as if the writers had forgotten the fact that humans can remember very well  memories that last for 50 years, a length of time a hundred times longer than "months." 

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. The same paper refers to another paper that "reported rates of [dendritic] spine eliminations in the order of 40% over an observation period of 4 days."