[HN Gopher] Memories are made by breaking DNA - and fixing it
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Memories are made by breaking DNA - and fixing it
Author : birriel
Score : 186 points
Date : 2024-03-28 09:26 UTC (13 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| darkerside wrote:
| What might this news imply about NSAIDS and their impact on
| forming memories?
| tomrod wrote:
| If it's not already known it opens an intriguing avenue for
| research.
| newzisforsukas wrote:
| > Participants using aspirin at baseline but not 5 years prior
| were more likely to develop cognitive impairment
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670291/
|
| Many related articles
| GlassOwAter wrote:
| Uh oh.. my doctors never told me this. That explains the last
| 10 years x.x
| hoc wrote:
| I immediately thought of that too. But also other influences on
| these reactions might be interesting to look at. From stress
| levels to metabolic issues including unbalanced supply with
| nutrients, infections, injuries. How do you remember your last
| exhausting argument or traumatic experience...
|
| Not sure about the actual mechanisms, but the idea of these
| kind of influences on individual memory formation is
| intriguing.
|
| After all, it's hacker news :)
| fragmede wrote:
| Shit, what does this mean for alcohol, and its ability to
| interfere with forming memories? We think we know why (alcohol
| affects glutamate which affects memory), but with this new
| information, does that change things?
| neom wrote:
| I was thinking recently about this thing I've encountered as
| a recovering alcoholic. I'm pretty sure I have a "drunk
| memories" brain and a "sober memories" brain - and I don't
| know I can access some of each while I'm in the other, that
| is to say sober memories when I'm drunk and drunk memories
| when I'm sober. I'd like to test this more, but I'm not
| willing to break my sobriety, so who knows if it's imagined
| or real.
| Terr_ wrote:
| > Research shows that individuals are less likely to
| remember information learned while intoxicated when they
| are once again sober. However, information learned or
| memories created while intoxicated are most effectively
| retrieved when the individual is in a similar state of
| intoxication.
|
| https://en.wikipedia.org/wiki/State-dependent_memory
| phkahler wrote:
| >> I'm pretty sure I have a "drunk memories" brain and a
| "sober memories" brain
|
| A pet hypothesis of mine is that maybe some of the brain
| chemicals act like an extra input to the neural network,
| and can be associated with various behaviors or memories.
| Lets say there are 5 of them which would create a 5
| dimensional "chemical space" you're operating in. Certain
| things can be remembered and associated with regions in
| this space. Being anxious, depressed, afraid, or whatever
| could be temporarily "cured" by shifting you out of the
| current region in this space. Which chemicals work would
| depend on your specific programming. This might explain
| people who have a fear response to positive emotional
| situations (they were traumatized by someone that otherwise
| gave them positive emotions that release certain
| chemicals). Just a weird hypothesis - I bet it's been
| researched but I haven't looked.
|
| Edit: One of the other responses to the parent post
| provided this:
|
| https://en.wikipedia.org/wiki/State-dependent_memory
| delichon wrote:
| Fascinating that the apparatus for memory between generations may
| also be used for memory within a generation. "Breaking" and
| "fixing" DNA could also be taken as a description of meiosis or
| mitosis. Perhaps there is some code re-use there.
| juitpykyk wrote:
| Neuron's DNA is not passed down, it would be quite logical for
| evolution to use neuronal DNA for weight storage.
| londons_explore wrote:
| Many nervous system behaviours do appear to be passed through
| genetics - for example, the ability to breathe, the reflex to
| avoid pain, etc.
|
| I suspect in the future we might find mechanisms beyond
| simple natural selection that allowed those mechanisms to get
| encoded in genetics.
| throwaway4aday wrote:
| I think you're talking to the wrong point. These memories
| aren't being encoded in germ cells, they are after the fact
| changes to DNA in mature neurons which have completely
| differentiated. I would think it's very possible at that
| stage of development for them to add or remove segments of
| DNA in order to encode new information not related to the
| development of the cell as long as it didn't interfere too
| much with parts that are actively used for the ongoing
| upkeep of cell activity. It would need to alter how the
| cell functions a little bit for the changes to modify the
| neuron's ability to process signals though.
| CuriouslyC wrote:
| I should note that studies have demonstrated that
| bacteria who have been modified not to be able to consume
| lactose will develop mutations that allow them to consume
| lactose again much more quickly than would be expected
| given the number of bacteria, the rate of random
| mutations and the size of the genome. It has been
| hypothesized that there is a cellular mechanism to
| control which portions of DNA are easily mutable,
| possibly through a combination of chromatin structure,
| epigenetic modification and changes to the local chemical
| environment via metabolism.
|
| This mechanism might exist in a scaled up form in humans.
| juitpykyk wrote:
| Isn't that what happens in antibody germinal centers?
|
| https://en.wikipedia.org/wiki/Somatic_hypermutation
| rolph wrote:
| bacterial plasmids are a common form of horizontal gene
| flow between individuals
| EVa5I7bHFq9mnYK wrote:
| Could they be transferred while in the womb?
| cjbgkagh wrote:
| I wonder if that means that each neuron could act as a mini
| turning machine
| rolph wrote:
| stop wondering and look deeper, youve bumped into the
| begining of an incredible journey. even individual
| protiens, exhibit rule paring.
| cjbgkagh wrote:
| My equivocation was to avoid downvote brigades that hit
| me last time I posited this same idea on HN.
| rolisz wrote:
| Check out Michael Levin's work, who's done some experiments
| with skin cell and has shown that they learn to do stuff.
| phkahler wrote:
| >> it would be quite logical for evolution to use neuronal
| DNA for weight storage.
|
| To pass that down you'd have to replicate the connectivity of
| the network for the weights to be relevant right?
|
| Related: The article doesn't say which DNA areas are broken
| and repaired. Nor does it say if they are modified. It seems
| like encoding weights in DNA would make them more robust but
| harder to change. If so, there should be a particular region
| where this is happening. Maybe there's a mapping between
| certain DNA areas and each synapse. That'd be really
| interesting.
| juitpykyk wrote:
| Neurons are not on the germ line, whatever happens to their
| DNA is not passed down to your children.
|
| There was another article in the recent years about neurons
| using RNA or DNA for storing information related to their
| activation patterns.
| rolph wrote:
| epigenetic inheritance is real
| axus wrote:
| The baby is connected to the mother's placenta for
| months, maybe information could be transmitted then. I've
| never heard anything to support that idea, though!
| JPLeRouzic wrote:
| In addition, most parts of the first cell of what will
| become a baby, come from the mother. This includes all
| DNA in mitochondria and another organelle that I don't
| remember the name.
| thro1 wrote:
| Wellcome. _Sometimes it may happen that familiar stem
| cells cross maternal-fetal barrier in placenta, persist
| somehow and start to function regardless, where stem
| cells are needed - usually in younger sibling coming from
| the older, in place of original cells, even in the brain
| - forming part of it as of another person (more or less)
| - interconnected but not the same.._
|
| _The Most Mysterious Cells in Our Bodies Don 't Belong
| to Us_ https://www.theatlantic.com/science/archive/2024/0
| 1/fetal-ma... (
| https://news.ycombinator.com/item?id=38861497 )
| ChainOfFools wrote:
| This always seemed like one of those little biological
| details, like the well known example of that nerve which
| loops all the way down a giraffe's neck and back again in
| order to connect two regions only a few inches apart,
| that shows that nature doesn't refactor.
|
| Because it seems like such a waste of the opportunity
| afforded by extended physical secueity and direct
| connection between mother and developing child, that some
| means of transferring a portion of the mother's learned
| knowledge, or at least some coarse grained abstraction of
| it, to the fetus, has never developed.
|
| The lazy dismissal of this question is just to say, if
| nature needed it, it would have evolved it, but this
| doesn't seem to hold in every case [0]. It seems rather
| that there was no way for such a capability to be built
| out of extending existing mechanisms, with the major
| barrier being the absence of nerve tissue in the
| umbilical cord, where higher level CNS connectivity might
| have evolved from as a foothold
|
| [0] and certainly doesn't account for what may happen in
| the future unless nature is completely done developing
| everything that could be developed. Nor does it
| incorporate the idea that human manipulation of our own
| biology is not itself also part of nature.
| RaftPeople wrote:
| Independent of this breaking/fixing, it's already known
| that DNA near the synapse (not necessarily in the neurons
| Soma) is modified via epigenetics to sustain the synapse at
| the new level.
|
| So yes, DNA epigenetic changes near the synapse are a key
| part of maintaining the "weight" or strength of that
| particular connection. ("key part" phrase because there is
| a lot of complexity and they haven't nailed it all down,
| there could be other "key parts").
| phkahler wrote:
| >> DNA epigenetic changes near the synapse are a key part
| of maintaining the "weight" or strength of that
| particular connection.
|
| What do you mean by "near the synapse"? Is there DNA
| outside the nucleus or something? Is there DNA that maps
| (corresponds to) the synaptic pattern of the neuron?
| RaftPeople wrote:
| Yes there is DNA outside the nucleus. The DNA near each
| synapse gets modified (epigenetic) based on activity in
| that physical area so it can produce the proper proteins
| to preserve the state of that synapse over the long term.
| logtempo wrote:
| so, my body is refactoring all the time?
| logtempo wrote:
| so, my body is refactoring all the time? Cool 8)
| api wrote:
| Antihistamines that cross the blood brain barrier make people
| feel stoned or tired because histamine does something entirely
| different in the brain from what it does in the rest of the
| body.
|
| Seems like there's a lot of code reuse in the brain. It
| operates almost like a different sort of biology encapsulated
| within an animal body.
| newzisforsukas wrote:
| https://www.nature.com/articles/s41586-024-07220-7
| throwaway4aday wrote:
| Interesting that this involves a response similar to an immune
| response to a pathogen. I've read a couple articles about
| alternate theories of Alzheimer's linking it to an increased
| immune response in the brain.
| Jensson wrote:
| > similar to an immune response to a pathogen
|
| Maybe that is the origin? Cells learning to counter different
| threats and communicating that information to other cells could
| be a plausible first step towards intelligence.
| dappermanneke wrote:
| there's no learning involved in the immune response in the
| brain. the brain is limited to the innate immune system, of
| which TLRs and their binding to conserved domains are
| basically the major component. there's no adaptive immune
| system that does "learning" here (and by learning in the
| adaptive immune system we mean recombination of antibodies,
| presentation of contents of each cell on the surface of the
| cells for antibodies to try and bind to, and the preservation
| of cells that carry antibodies that bound to something
| successfully as memory cells to enable long term immunity)
| 2snakes wrote:
| This does not seem right. From what I recall, there is some
| sort of memory for the immune system.
| dappermanneke wrote:
| you should reread what I wrote
| ofslidingfeet wrote:
| Terrence McKenna called it.
| firtoz wrote:
| Please elaborate.
| neom wrote:
| Terrence talked a lot about everything as code, and DNA being
| that code, or part of that code anyway. He's talked about it
| a lot in different ways, so I'm not sure what talk OP is
| specifically referring to. He gave a couple of talks that are
| related to I Ching, it might be in detail in one of those.
|
| https://www.youtube.com/watch?v=Zk8GsaRA6aY
| ofslidingfeet wrote:
| There was at least one talk where he clearly speculated that,
| spirituality aside, he thinks DNA plays a role in long term
| memory formation just because that's physiologically the only
| place memories could persist. Unfortunately the only record
| of this I knew about has been deleted from youtube.
| Vox_Leone wrote:
| Although I have nothing substantial to contribute to the topic, I
| can't help but notice the beautiful mess of the neural field
| shown in the image; a reminder of the complexity of the real
| world and the challenges that still remain. Very far from our
| organized models arranged in layers of 'objects' and the didactic
| diagrams containing two neurons, or even convolutional network
| diagrams. Which brings to mind the good Professor "it must be
| made as simple as possible, but not simpler".
| kenjackson wrote:
| Dumb question from a very last biology person. I thought memories
| were stored in the brain and The brain retrieved them. How does
| the brain get the data from the DNA for long term memories?
|
| The article seeks like a simple explanation, but it still doesn't
| make sense to me.
| pazimzadeh wrote:
| Like most cells, brain cells have DNA. I don't think this is
| saying that the memory is directly encoded in the DNA, but that
| when a memory is formed (in this case a fear response), that
| can lead to breaks in neuronal DNA, and loose DNA in cells
| triggers the immune system, which then tries to repair the
| damage.
| kenjackson wrote:
| And the repairing of this broken DNA by the immune system
| somehow strengthens the encoding of the memory? But the DNA
| itself doesn't actually capture any of the memory. Is that
| accurate?
| namaria wrote:
| > And the repairing of this broken DNA by the immune system
| somehow strengthens the encoding of the memory?
|
| "In other words, during damage-and-repair cycles, neurons
| might encode information about the memory-formation event
| that triggered the DNA breaks, she says."
|
| I'd say the researchers speculate something like what you
| said. The inflammatory response and the activities involved
| in DNA repair seem correlated with long term memory
| formation.
| rolph wrote:
| so far its a correlate, not yet determined to be a direct
| mechanistic causation
| cjbgkagh wrote:
| Huh, I wonder if this is why RCCX genes associated with
| autoimmune conditions / inflammation is also associated with
| higher IQs.
| lupire wrote:
| The OP observation is that memory formation includes damaging
| DNA and repairing it , either as a side effect or as a
| mechanisms of memory formation, but it's unclear which.
|
| Generalized autoimmune disorders probably wouldn't increase
| memory formation as a mechanism -- that effect would be
| "memorizing" "white noise", not a specific meaningful memory
| (neuron path).
|
| But perhaps high IQ individuals, associated with
| hyperactivity/high metabolism of some kind, have more/faster
| neuronal activity, cause more of this DNA damage then the
| average person experiences, to the point where it has
| detrimental inflammatory effects?
| cjbgkagh wrote:
| I have multiple TNXB SNPs, tested very high IQ, and have
| debilitating levels of inflammation with ME/CFS. Wasn't so
| bad when I was younger but got really bad in my 20s and 30s.
| I have it under control now with quite an exotic mix of
| medications.
|
| My memory is pretty insanely good as is my ability to learn
| new things. I had previously thought it was due to interest
| and acumen but have come to accept that I am fortunate in
| ways that others are not - the difference being that I no
| longer blame others inability to learn as much or as quickly
| on an apparent laziness or lack of interest.
|
| ME/CFS is very debilitating though so most people with this
| will probably just fade away in their 20s and 30s. There are
| ways to treat it that I wish more people knew about.
|
| Edit; I should mention that too much inflammation is
| associated with brain fog which inhibits working memory and
| memory formation. Brain fog is one of the many core symptoms
| of ME/CFE.
|
| It would make sense if the body is optimizing childhood
| learning over long term health.
| wburglett wrote:
| What approaches are there for treating ME/CFS?
| cjbgkagh wrote:
| It depends on the cause but for the TNXB subset which is
| probably a big chunk of them there is hGH peptides,
| Testosterone replacement therapy (TRT), low dose
| modafinil, amitriptyline, IGF-agonists
| (semaglutide/ozempic), low dose naltrexone (LDN), TUDCA,
| eliminate sugar (including fruit) from diet, melatonin,
| UV-A light therapy in eyes during the day, blue light
| blocking glasses at night, sleep hygiene, lower stress
| lifestyle, supplemental T3 hormone, caffeine, and
| resistance exercise. Cardio above a fast walk should
| probably be eliminated due to post exertional malaise
| (PEM). The cause of PEM is a tough one that I'm still
| working on.
| wburglett wrote:
| For PEM specifically have you had any experience with
| pyridostigmine or cumin (the kitchen spice)?
| cjbgkagh wrote:
| I've tried Enalapril which seems similar to
| Pyridostigmine, I ended up with pretty strong blood
| pressure swings. I'll check it out though. The problem
| with testing PEM for me is the extreme downside if the
| test fails, it could be many months before I'm good
| again. Instead of trying these things myself I'm more apt
| to crowd source from people who I know that also have PEM
| and more open to testing it.
| tamimio wrote:
| How does that work in visual memory, does it break and fix it too
| and that quickly? I have strong visual memory that I remember
| back in school I used to remember the page and it's page number
| just by looking at it for few seconds, and if I saw a face for a
| second even randomly anywhere, I can recall when and where for a
| long period after.. I find it hard to imagine or rather scary all
| that is breaking/fixing the dna..
| softfalcon wrote:
| My guess would be that it's not all happening at once as you
| have short and long term memory.
|
| The simplest analogy is that your short term memory is a buffer
| that doesn't use DNA, but a limited electro chemical storage of
| new present-moment information.
|
| Then it is transcribed through several steps of ever longer
| term storage methods in the brain. Some of which require sleep.
| sva_ wrote:
| The article doesn't seem to claim that this is the only
| mechanism, even if the title seems to suggest so.
| RaftPeople wrote:
| There is a lot of activity with DNA for long term potentiation
| even without this breaking/fixing stuff. Learning requires
| epigenetic modifications to DNA in the neuron. DNA near the
| synapse (not necessarily in the Soma) is altered to produce the
| proteins that sustain the synapse at new level.
| bugbuddy wrote:
| I am surprised no one has referenced the Animus here.
| Terr_ wrote:
| While I see the association, there's no reason to think that
| DNA from a billions of nerve cells in your brain is somehow
| being synced to specific single cells. (Haploid cells that are
| missing half the usual load of DNA, to boot.)
| lukeinator42 wrote:
| Interestingly, although the hippocampus plays a massive role in
| memory consolidation, memories are ultimately distributed
| throughout the cortex.
|
| I'm curious whether this mechanism generalizes to all neurons or
| is specific to how the hippocampus can learn quickly, especially
| since the hippocampus is the one place where neurogenesis has
| been found in adults.
| bjornsing wrote:
| What evidence is there for this distribution over the whole
| cortex hypothesis?
| noworld wrote:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526749/#:~:tex.
| ...
| lukeinator42 wrote:
| The classic study of patient H.M., who had his hippocampus
| removed, showed that the hippocampus isn't where memories are
| stored long-term
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC497229/ (this
| was one of the first studies to discover the role of the
| hippocampus in memory). H.M. was still able to recall
| memories from before the surgery, and numerous animal and
| human studies have demonstrated this too.
|
| The hippocampus connects to most of the cortex, and there is
| an entire research area looking into hippocampal replay and
| how it facilitates consolidation, but there definitely isn't
| a singular place where memories are stored in the brain long-
| term.
| namero999 wrote:
| As Michael Levin's work shows, one doesn't even need a brain
| or a nervous system for memory
|
| https://www.scientificamerican.com/article/brains-are-not-
| re...
| nicman23 wrote:
| damn assassin's creed got it right?
| begueradj wrote:
| That's something we can use to interpret what is mentioned in
| "The Talent Code" book: https://www.amazon.com/Talent-Code-
| Greatness-Born-Grown/dp/0...
| pfdietz wrote:
| Does this mean education is carcinogenic?
| armchairdweller wrote:
| I found one of the most interesting aspects of memory to be its
| non-locality. There were a lot of experiments in the 20th century
| (lesions etc.) showing that memory is fundamentally non-local.
| You could remove large parts of brains and the memories were
| still there. This is difficult to explain with "local" / neural-
| network-like theories of memory. If you lesion specific parts of
| GPT4, the "memory trace" will be gone.
|
| I find this incredibly interesting. Is this still the primary
| view?
|
| The hippocampus is involved in formation of new memories. Without
| it this process is not working at all.
| LarsDu88 wrote:
| Interesting. I think TLR-9 stands for toll-like receptor 9. And
| these toll proteins were originally studied in fruit fly dorsal
| ventral patterning and also play a role in the innate immune
| system which we share with insects.
|
| If this study is right (who knows if it will end up being
| reproducible), then this would be a great example of how
| evolution recycles existing proteins to "invent" new stuff.
|
| Toll proteins were probably originally involved in body pattern
| formation, were recycled into a role in innate immunity, and
| finally in mammals may also play a role in triggering an immune
| response based DNA damage repair event that plays a role in
| memory formation.
| newzisforsukas wrote:
| Or a innate signal recognition of anything that is worth
| remembering (sensory stimuli, internal stimuli, etc)
| suoduandao3 wrote:
| interesting. Brings to mind this study:
|
| https://sheldrake.org/files/pdfs/papers/An-experimental-test...
|
| Memory and DNA are both weird. As an appreciator of weirdness
| it's fun to see that there's some kind of connection between the
| two. Anyone know if there a theory of weirdness where it would
| compound?
| thro1 wrote:
| Every neuron in the brain has unique DNA and ancestorship -
| _ongoing record of neuronal life history_.
|
| https://www.science.org/doi/10.1126/science.aab1785 (2015) :
| _Somatic mutations create nested lineage trees, allowing them to
| be dated relative to developmental landmarks and revealing a
| polyclonal architecture of the human cerebral cortex. Thus,
| somatic mutations in the brain represent a durable and ongoing_
| record of neuronal life history _, from development through
| postmitotic function._
|
| https://www.scientificamerican.com/article/scientists-surpri...
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