Neurons, DNA, Memory and Learning

[icakeov]

Hello

I am not an expert in this field but I am really hoping to understand as much as I can about the concepts described in my questions below. I might be using some improper jargon and expressions, so I apologize if some things are incorrect or confusing.

#1 Do all the neurons have the same expression of the DNA that they contain? (DNA is the same in all of them, right?) Do the neurons cells get instinct behaviors directly from the DNA that they contain?

#2 I suppose the behaviors that are learned (rather than instinctive) come from environmental stimulus and are expressed in combination with the pre-programmed genetic instinct. Also, I imagine that the learned behavior needs to happen a bunch of times through a given batch of nerve cells in order for the behavior to be remembered by the nerve cells' pathway that is being created. Is there a certain amount of times before this pathway becomes permanent? Does the pathway always stay more or less the same (since the same nerve cells would need to be stimulated, right?)? And is there a limit to how many different "stimuli"/"pieces of information" a give nerve cell can "transmit"/"hold" (I read somewhere it can be anywhere from 1000 to 10,000!)?

#3 Once a nerve cell "adopts" a learned behavior, and it becomes "permanent", can it ever "forget"/"discharge" it? Or does the "charge"/"information" stay in that nerve cell for the rest of the person's life? Or does it slowly "fade" until it totally perhaps eventually dissipates?

#4 I read somewhere that a new "batch" of nerve cells need to override an old, habituated, unwanted behavior, which actually never really "goes away", and merely stay "overridden", and can in fact return back if the new habituated behavior doesn't "hold-up". Is this true? And if it is, is this new "information" "stored" within the same batch of neurons, along the same pathway that held the "old" memory or is this a whole new batch of neurons, with a totally new pathway, with the "new" information somehow "overriding" the other neurons that hold/transmit the "old" behavior? (or both?)

Many many thanks!

 

[Dr. Courtney]

Every cell in the body has the same dna.

 

[Ygggdrasil]

#1 Do all the neurons have the same expression of the DNA that they contain? (DNA is the same in all of them, right?)

Every cell in the body has the same dna.

While all cells in the body contain largely the same DNA, if certain mutations happen during development (i.e. after the initial cell division when the embryo splits into the two cell stage), then these mutations will only occur in a subset of the cells in the body. Such mutations cause a phenomenon called mosaicism. Interestingly, mosaicism within the brain caused by the insertion of retrotransposon sequences within the DNA of neurons has been postulated as a http://www.nature.com/nrn/journal/v15/n8/full/nrn3730.html.

As for the general questions about learned vs instinctual behaviors, here's an old PF thread that you might find interesting: https://www.physicsforums.com/threads/instinct-encoded-in-dna.602902/

 

[icakeov]

Thanks for your response Ygggdrasil,
I didn't realize that DNA can mutate within the body in its lifetime. And that it happens in neuron cells. Is this something that happens as a rule of thumb or more of a rare occurrence with neurons?
Thanks for the link to the old PF thread, that thread is in fact how I stumbled upon this website when I googled about this topic. It didn't quite answer the questions that I had so I thought I'd post a new one here.

 

[DiracPool]

#1 Do all the neurons have the same expression of the DNA that they contain? (DNA is the same in all of them, right?)

All neurons contain the same DNA, but the "expression" of that DNA depends on what type of nerve cell is being produced. Obviously different genes are expressed depending on whether you're a mitral cell, amacrine cell, pyramidal cell, or a GABA-ergic inhibitiory interneuron.

Do the neurons cells get instinct behaviors directly from the DNA that they contain?

That's an oversimplistic concept of the way neurons and neuron networks work. The short answer is no.

is there a limit to how many different "stimuli"/"pieces of information" a give nerve cell can "transmit"/"hold" (I read somewhere it can be anywhere from 1000 to 10,000!)?

I think neurons in vitro can be artificially stimulated to up to 1000 pulses per second; there is a refractory period that places a limit there. However, these extreme frequencies are almost never seen in in vivo populations of neurons. The typical neuron in the mammalian brain pulses at less than 10 per second, it's the collective activity of 100's of millions of neurons all pulsing at about 3-4 spikes per second that drive brain dynamics and learning.

#3 Once a nerve cell "adopts" a learned behavior, and it becomes "permanent", can it ever "forget"/"discharge" it? Or does the "charge"/"information" stay in that nerve cell for the rest of the person's life? Or does it slowly "fade" until it totally perhaps eventually dissipates?

Nothing is "permanent" in brain dynamics. And you're looking at it in the wrong way, something like an atomistic perspective of brain function. Learned behaviors are the the product of modified "Hebbian cell-assemblies;" they are not a product of the biology and genetics of single neurons. Rewarded behaviors strengthen the synaptic connections between neurons which facilitate the future expression of those behaviors, and unrewarded behaviors lead to the extinction of those behaviors through atrophy of those connections.

is this new "information" "stored" within the same batch of neurons, along the same pathway that held the "old" memory

Yes

or is this a whole new batch of neurons, with a totally new pathway, with the "new" information somehow "overriding" the other neurons that hold/transmit the "old" behavior?

No

The brain doesn't work like a computer, there are no separate sectors and hard drives to store separate information. Everything is stored, superimposed, on the same medium. Everything is constantly being written and overwritten, so practically, no, no memory is ever completely lost, but it can be so weakened that it is effectively lost, and given the right conditions an effectively lost memory can be regained or "reignited," so to speak.

 

[atyy]

Thanks for your response Ygggdrasil,
I didn't realize that DNA can mutate within the body in its lifetime. And that it happens in neuron cells. Is this something that happens as a rule of thumb or more of a rare occurrence with neurons?
Thanks for the link to the old PF thread, that thread is in fact how I stumbled upon this website when I googled about this topic. It didn't quite answer the questions that I had so I thought I'd post a new one here.

Neurons might have different DNA, but if one wants a very solidly established case, one can look at VDJ recombination.

 

[atyy]

#2 I suppose the behaviors that are learned (rather than instinctive) come from environmental stimulus and are expressed in combination with the pre-programmed genetic instinct. Also, I imagine that the learned behavior needs to happen a bunch of times through a given batch of nerve cells in order for the behavior to be remembered by the nerve cells' pathway that is being created. Is there a certain amount of times before this pathway becomes permanent? Does the pathway always stay more or less the same (since the same nerve cells would need to be stimulated, right?)? And is there a limit to how many different "stimuli"/"pieces of information" a give nerve cell can "transmit"/"hold" (I read somewhere it can be anywhere from 1000 to 10,000!)?

It depends on what you mean by permanent. There are almost certainly no organisms that are immortal, because of the accelerated expansion of the universe http://arxiv.org/abs/hep-th/0106109 :P

More seriously, let's say you define some idea of "permanent". Then there are clearly behaviours or memories that can be learned in one shot, while others need many repetitions.

Here is an example of learning from one time: http://www.ncbi.nlm.nih.gov/pubmed/11572949 (free link to article at the top right).

#3 Once a nerve cell "adopts" a learned behavior, and it becomes "permanent", can it ever "forget"/"discharge" it? Or does the "charge"/"information" stay in that nerve cell for the rest of the person's life? Or does it slowly "fade" until it totally perhaps eventually dissipates?

In a dish and in theory yes, so this probably happens, but off the top of my head, I don't know a solid demonstration that this is true for a behaviour in an animal. http://thebrain.mcgill.ca/flash/i/i_07/i_07_m/i_07_m_oub/i_07_m_oub.html

#4 I read somewhere that a new "batch" of nerve cells need to override an old, habituated, unwanted behavior, which actually never really "goes away", and merely stay "overridden", and can in fact return back if the new habituated behavior doesn't "hold-up". Is this true? And if it is, is this new "information" "stored" within the same batch of neurons, along the same pathway that held the "old" memory or is this a whole new batch of neurons, with a totally new pathway, with the "new" information somehow "overriding" the other neurons that hold/transmit the "old" behavior? (or both?)

Yes, this can happen, eg. in the experiment of Packard and McGaugh: http://www.ncbi.nlm.nih.gov/pubmed/8673408.

They trained rats to do something. After 8 days the animal did it using method A. After 16 days the animals did it using method B. Was it because method B had erased method A, or was method A still there and method B was preferred? Packard and McGaugh silenced a part of the brain. The silencing made the rats revert to method A, indicating that method A was still stored in the brain.

 

[Ygggdrasil]

I didn't realize that DNA can mutate within the body in its lifetime. And that it happens in neuron cells. Is this something that happens as a rule of thumb or more of a rare occurrence with neurons?

It seems like retrotransposon elements may be more active in the brain than in other tissues. Scientists are still working out the best techniques to detect these retrotransposition events, so there are widely varying estimates as to how common these events are in neurons.

In any event, even cells with identical DNA can have different patterns of gene expression. These are though to be due to differences in the way the genes are packaged. Cells can mark specific regions of the genome with certain chemical tags on the DNA or on the proteins that package the DNA which can tell the cell to turn the genes on or turn the genes off. These epigenetic changes probably underlie most of the differences in gene expression between different individual neurons.

Neurons can also have different levels of gene expression in different parts of the neuron. Neurons traffic mRNAs and ribosomes to their various axons and dendrites, and local neuronal activity at specific synaptic spines or terminals may change which genes are made at that synapse and only that synapse. So gene expression can not only vary from cell-to-cell, but in neurons at least, gene expression can also vary within different regions of the cell.

 

[gravenewworld]

You should look up the theory of allosteric modulators...which is absolutely fascinating in my opinion. Allosteric modulators, in theory, have a built in cap for the limit of the their activity, which is quite different than agonists or antagonists (the more you give, the more response you usually see). One idea that people have is that if you could develop allosteric modulators for targeting various things in the brain, you could give massive doses of a drug and have a built in safety mechanism for toxicity, but the real power of allosterism is the fact that you might be able to obtain a uniform response from all neurons. That's something you can not achieve with our current regimen of drugs that target the brain, and it could address how you treat brain diseases when each neuron might be behaving differently due the uniqueness of cell physiology profiles at any given moment in time (some neurons might die at a high dose of a drug that is needed to treat diseased neurons, but if you had an allosteric modulator, you could cap the max response and achieve a uniform treatment amongst all cells).

 

[icakeov]

Thanks so much for your response DiracPool, it clarified so many things!

... the collective activity of 100's of millions of neurons all pulsing at about 3-4 spikes per second that drive brain dynamics and learning.

- And what about different types of information that they can process? Is there a limit to the variety of tasks it can process collectively?

... and unrewarded behaviors lead to the extinction of those behaviors through atrophy of those connections.

- I am guessing that atrophy here means that connections really never "die" but just get weakened or unused (until they might get stimulated again sometime in the future as you pointed out in an answer further in the thread)

 

[icakeov]

Thanks atyy!
Great point about learning happening quick or slowly depending on the circumstances.
Also, your http://thebrain.mcgill.ca/ link had another "procedural memory" reference to different types of learnings were defined, very helpful!
And thanks for the Packard and McGaugh, exactly an answer I was looking for!

 

[atyy]

Also, your http://thebrain.mcgill.ca/ link had another "procedural memory" reference to different types of learnings were defined, very helpful!

That's one of the most celebrated and important discoveries about memory - made by Brenda Milner's observations on H.M. The other major discovery she made with Scofield, the surgeon, is that the medial temporal lobe stores long-term memory, but not the super-long-term memory. See 10:05 for the discovery of procedural memory.



What Brenda Milner looks like in real life.

And thanks for the Packard and McGaugh, exactly an answer I was looking for!

Another related phenomenon is http://www.ncbi.nlm.nih.gov/pubmed/12464700.

I should mention this very interesting paper about the concepts involved in extinction as new learning versus unlearning: http://www.ncbi.nlm.nih.gov/pubmed/15466310.

 

[icakeov]

These are incredible resources! Answered so much! Thanks again atyy!

 

[icakeov]

I am still curious about the relationship between innate and learning behaviors and the influence of DNA on our behavior. I have found this article below and I especially like the image by the end that displays the percentual relationship between innate and learned behaviors in different animals. I was wondering if this is an accurate explanation of how the two different types of learnings develop.
http://www.cals.ncsu.edu/course/ent425/tutorial/Behavior/

 

[atyy]

I am still curious about the relationship between innate and learning behaviors and the influence of DNA on our behavior. I have found this article below and I especially like the image by the end that displays the percentual relationship between innate and learned behaviors in different animals. I was wondering if this is an accurate explanation of how the two different types of learnings develop.
http://www.cals.ncsu.edu/course/ent425/tutorial/Behavior/

I wouldn't take the percentages too seriously. Nonetheless, there are behaviours that are more "innate" and others that are more "learnt". But what is learning? There is no universal agreement, but a simple one is a change in behaviour as a result of experience.

This definition is very broad, and if one thinks about it, it makes development and learning a continuum. http://bioteaching.com/phenotypic-plasticity-2/

 

[icakeov]

Here are some of understandings that I've gained so far (I must admit I was slightly struggling with understanding the explanations of memory extension and spontaneous recovery paper(s)):

- When a brain learns a fear response to a stimulus, the new stimulus that is not fear induced is a new memory. I get that. Does the experiment show that both behaviors can continue to exist independently, depending on wether they are stimulated or not? So at times when the stimulus is fear induced, the original memory will be reinforced, and similarly if the stimulus is not fear induced, the other "stored" memory will be induced?
It seems like any memory will become habituated as long as there is a stimulus to reinforce it enough times, and once it is habituated, then the behavior can propagate, as long as it is not stopped by another behavior? And if the reinforcement stops (or some other behavior overrides it), the habituated behavior will slowly start to "fade".

Furthermore, I understand that neurons (and groups of neurons) can have a certain amount pulses per second, but I am still unclear about whether a certain neural path can "hold" more than one learning? The way I get it so far is that learning can build on top of each other, using one learning to learn more. For example, if I meet someone who has a name similar to a famous actor, I will associate that person to all the movies that I saw with that actor. So new neural pathways are now built on top of (or in "collaboration" with) the previous pathways that held previous knowledge. I wonder if these same neural pathways can also be in charge of knowing other names, or some other types of information. Maybe certain cells can only take on only explicit or only implicit behaviors? And if so, would there be a limit if they can take on more behaviors?

 

[atyy]

Furthermore, I understand that neurons (and groups of neurons) can have a certain amount pulses per second, but I am still unclear about whether a certain neural path can "hold" more than one learning? The way I get it so far is that learning can build on top of each other, using one learning to learn more. For example, if I meet someone who has a name similar to a famous actor, I will associate that person to all the movies that I saw with that actor. So new neural pathways are now built on top of (or in "collaboration" with) the previous pathways that held previous knowledge. I wonder if these same neural pathways can also be in charge of knowing other names, or some other types of information. Maybe certain cells can only take on only explicit or only implicit behaviors? And if so, would there be a limit if they can take on more behaviors?

http://www2.le.ac.uk/centres/csn/publications-1/Publications/scientificamerican0213-30.pdf
Brain Cells for Grandmother
R. Quian Quiroga, I. Fried, C. Koch
Scientific American 308: 30-35, 2013

The number of memories depends on how the neurons are connected, how the information is encoded and read out etc. Here is a relevant quote from the above article:

"Using statistical methods, Stephen Waydo, at the time a doctoral student with one of us (Koch) at Caltech, estimated that a particular
concept triggers the firing of no more than a million or so neurons, out of about a billion in the medial temporal lobe. But because we use pictures of things that are very familiar to the patients in our research—which tend to trigger more responses—this number should be taken strictly as an upper bound; the number of cells representing a concept may be 10 or 100 times as small, perhaps close to Lettvin’s guess of 18,000 neurons per concept."

 

[icakeov]

Fantastic article! And fantastic references to each of my questions atyy! Thanks again.

 

[icakeov]

Here is another question on the general topic above:
Are there neurons in the brain that haven't been "fired up" yet and are waiting until a specific learning is to be in line? Or neurons always firing up, but not necessarily with any useful information to retain? How does this work?
For example, when a baby is born, what "state" are all the neurons in? Are they are ALL active from the get go and start building neural pathways through the whole brain? Or is it more that certain parts of the brain are "dormant", if that's the right word.
For example, considering that explicit memories don't start forming after a couple of years after birth, does that mean that, for example hippocampus is inactive during all that time? (I am assuming that hippocampus is only in charge of explicit memory).

 

[icakeov]

Yet another question I have is about the triune brain. (pardon my ignorance if I got lot of this wrong)
Do reptiles have any form of a limbic system or is that only present in mammals? Similarly, do only primates have a neocortex, or do the rest of the mammals have a somewhat developed neocortex?
Do fish, amphibians (and so on) have a reptilian brain too? Or some form of it? Do they have anything at all similar to a limbic system or neocortex?
Now, If reptiles (or some other similar species group) only have a reptilian brain but no limbic system or neocortex, would that mean that they can't think and cannot feel? And does that mean that they (and all animals apart from mammals) don't think and don't have feelings and purely function based on survival, "reptilian" instinct?
And how does this affect memory and learning in other species? Is implicit memory stored in the "lower", reptilian and limbic structures and is explicit memory present in only the neocortex? And what about learning by imitation? Which parts of the brain can learn through imitation, and as a result, are there certain species that can learn through imitation and some can't?

 

[DiracPool]

Are there neurons in the brain that haven't been "fired up" yet and are waiting until a specific learning is to be in line? Or neurons always firing up, but not necessarily with any useful information to retain? How does this work?

All neurons are always active in the brain all the time, or else they typically die or get "pruned." Even "at rest" they always maintain some basal pulse frequency.

For example, when a baby is born, what "state" are all the neurons in? Are they are ALL active from the get go and start building neural pathways through the whole brain?

Yes

Do reptiles have any form of a limbic system or is that only present in mammals?

You ask a lot of questions here that aren't as black and white and the questions suggest. I recommend two fairly easy to read books for the lay person, Streidter's Brain Evolution and Swanson's Brain Architecture.

https://www.amazon.com/dp/0878938206/?tag=pfamazon01-20

https://www.amazon.com/dp/019537858X/?tag=pfamazon01-20

Very generally, though...

Do reptiles have any form of a limbic system or is that only present in mammals?

The best way to look at this is that reptiles have a homologue of the mammalian limbic system and this can vary from species to species.

Similarly, do only primates have a neocortex, or do the rest of the mammals have a somewhat developed neocortex

All mammals have a neocortex. The only major distinction is that Eutherian (placental) mammals have a dedicated motor cortex, or M1 region, and non-placental mammals such as the marsupials (e.g., kangaroo) do not.

Do fish, amphibians (and so on) have a reptilian brain too? Or some form of it? Do they have anything at all similar to a limbic system or neocortex?

There is a debate as to what extent the amphibian brain has some homologous features to what may be referred to as a canonical mammalian limbic system. For example, there is some evidence that frogs have a homologue to the amygdala.

And how does this affect memory and learning in other species? Is implicit memory stored in the "lower", reptilian and limbic structures and is explicit memory present in only the neocortex?

When you talk about "thinking and feeling" and "explicit versus implicit" memory, you are now venturing into the wide field of neuropsychology, where the answers are much less clear cut than anatomical considerations.

 

[atyy]

(I am assuming that hippocampus is only in charge of explicit memory).

And how does this affect memory and learning in other species? Is implicit memory stored in the "lower", reptilian and limbic structures and is explicit memory present in only the neocortex? And what about learning by imitation? Which parts of the brain can learn through imitation, and as a result, are there certain species that can learn through imitation and some can't?

Just to echo DiracPool's point that "explicit" and "implicit" are human terms, which is very difficult to generalize to animals, although it is discussed, eg. http://www.ncbi.nlm.nih.gov/pubmed/23964879 (sorry, no free full text this time). While waiting for the experts to settle on what concepts they find most general, one can say that we learn many different things, and these involve changes in different parts of the nervous system. So one may prefer to say eg. "hippocampal-dependent memory" rather than "explicit memory".

 

[Feeble Wonk]

I think it might be helpful for you to think about memory/learning/mental functions as a functional process rather than a structural one. You shouldn't think of memories or learned behaviors as being "stored" in a neuron like they're a substance that is bottled. During the learning process, it's not so much the nerve that changes as much as it is the synaptic connections. What changes is how the neuronal network functions.

 

[Feeble Wonk]

Thanks for your response Ygggdrasil,
I didn't realize that DNA can mutate within the body in its lifetime. And that it happens in neuron cells. Is this something that happens as a rule of thumb or more of a rare occurrence with neurons?

...and, for whatever it's worth, mutations can occur anytime a cell undergoes binary reproduction during the transcription phase. Cancer is an example of this of course. They're more common in rapidly reproducing cell lines, but not uncommon in neuronal tissue.

 

[icakeov]

Thanks Feeble Wonk!
The analogy of thinking of it as synaptic connections and network functions really helps. Would it be fair to think of memories as "electric charge" and network functions to a specific "installed software"? Would that be at least to a degree more analogous?

 

[icakeov]

And thanks DiracPool. I am really realizing after reading all the answers here why it is said that the brain is such a complex system.
With the way it works, it sounds like, the brain as a whole is constantly active, and depending on what environment a specific organism is in, it will learn different things, perhaps not the best learning at times when the brain is not exposed to it, but the neurons are firing regardless, hungry to accumulate learning.

 

[Feeble Wonk]

In regard to innate/instinctual behavior, you might think of the neurological function (synaptic connections) being hard wired from birth.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337482/

 

[Feeble Wonk]

Thanks Feeble Wonk!
The analogy of thinking of it as synaptic connections and network functions really helps. Would it be fair to think of memories as "electric charge" and network functions to a specific "installed software"? Would that be at least to a degree more analogous?

I'm not sure about the "electric charge"/memory thing. Not sure I see a similarity there. But memory is a funny thing for lots of reasons, subtly different from basic learned behavior. Aside from that, there's both short term and long term memory, and both psychological and physiological components. Wiki does a pretty good job of general discussion.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337482/

 

[icakeov]

Hi Feeble Wonk, I found this video that describes the evolution of the brain and describes neural impulses as electrical ion impulses. And also they explain that
synapses enable the storing of long term memory.

I am still trying to find a way to understand how long term memory actually gets stored. It is not "stored", and it is not analogous to an "electrical charge". And it is not stored in the neuron, but rather through the synapses, and it needs to be learned over and over again for it to become solid long term memory.
So when I think of learning as a function, I am still at a loss where and how that function gets "retained" and, for a lack of a better word, "stored"?

 

[DiracPool]

So when I think of learning as a function, I am still at a loss where and how that function gets "retained" and, for a lack of a better word, "stored"?

It gets stored as a pattern of reinforced synapses that get reinforced when reward accompanies a given behavior. Rewarded behaviors are conditioned to a "go" mechanism that facilitates the expression in the musculature of such rewarded behaviors. Punished behaviors are conditioned to a "stop" mechanism which inhibits the expression of said behaviors. Behaviors that are neither reinforced nor punished typically get "extinguished" through atrophy of their synaptic connections.