Best way to understand neurons -> behavior? Options

[Palaver87]

Neuroscience grad student here, trying to figure out how to "solve the brain" like really. This may be a pretty wishy-washy question, but what do you guys think is the best way to understand how many individual neurons produce behavior especially in humans/primates? There is fMRI, but that only seems to show us where activation occurs and now how the individuals neurons are working. There is electrophysiology, but the brain is composed of billions of neurons, and I feel like most spend a lifetime just studying a small circuit. Electrophysiology (perhaps calcium imaging or multielectrode arrays) + machine learning is the best I can come up with. A professor told me that I should look at simple model organisms and extrapolate to humans. Not sure if you really need 1000 people working from cellular to imaging for many years to figure it out :-/

[lucid_dream]

Many people have devoted a lot of time to your question. My own conclusion:

What is needed in neuroscience is an Ultrastructural Mapping of the Whole-Brain, aka the 'ultrabrain', to see precisely how individual neurons are wired together and their morphologies. Granted, this approach completely excludes functional mapping (for the time being), but sometimes you need to sacrifice breadth for depth, and having this ultrabrain would provide a treasure trove of data for circuit analysis and functional inference, and for interpretation of functional data.

If this sounds a lot like 'connectomics', it is (in a sense). However, the term 'connectomics' has been conflated, and is now used in practice to refer to completely different things, from ultrastructural (EM) mappings to DTI/MRI mappings, which differ in spatial scale of resolution over a million-fold (i.e., EM resolution = 1 nanometer, DTI/MRI resolution = 1 millimeter). Hence the new term (ultrabrain = ultrastructural mapping of the whole-brain), in order to prevent confusion about meaning.

The ultrabrain is the project I've been working on. There will be a more substantial information update in the coming weeks.

[astroidea]

Fire together, wire together.

Associative memory

[Zarathustra]

I wonder what you guys expect from a rebuild computer with the same circuits and maybe the ability to creat
spontaneous action potential. What do you try to find, to measure, datas about the conciousness, an articificial intelligence? What kind of expression gives you the feedback, calculation processes of a computer you gave the basis to answer?

In my opinion there are very hard porblems of the consciousness such a model can`t solve. The problem of subjectivism, of associative learning, and the fact that the neurophysiologic circuits are integrated in a biological system, a cell, which is connected to other cells not only over synapses. This cell for itself has a memory, houskeeping actions, and barriers.
The hole process of conciousness can be copied by an computer, when you just give him the hardware. There are maybe solvations in medical cases like locked-in, patients with neglect, patients in coma, which can offer some aspects which differ in beiing a concious person with a history, or being a wiring organ with no conciousness.

But my main question is still, what do you expect to find??

[Flex]

I don't think it will be as simple as even mapping the brain. I am sure there will be some (HUGE) epigenetic components. You can't really consider how the brain is wired, without also considering how it is rewired.

[Zarathustra]

I don't think it will be as simple as even mapping the brain. I am sure there will be some (HUGE) epigenetic components. You can't really consider how the brain is wired, without also considering how it is rewired.

thanks, thats a nice phrase, totaly right, totally not helpful. To understand the mapping of the brain and rebuild it would be interesting, but should we trust that kind of obvervations relating to human conciousness. It might be usefull to understand the abilities to integrate systematicelly and produce new functions in that kind of manner, but it says nothing about the consciounsness, the sense of it or human behavior.

[Flex]

Well in my opinion, I personally think consciousness can be pretty well understood with the right definitions.

For me, "consciousness" is the ability to recognize and adapt to the environment. When a child is born, their brain already has a bunch of circuits hardwired. These enable the organism to survive, but I do not believe they enable consciousness (at least not on higher levels). This being said, only those circuits which exhibit plasticity IMO are capable of conscious processes.

We already have a descent idea of how the brain accomplishes this. Plasticity occurs when you have repeated depolarization. So basically you are faced with a stimulus, you respond, and if the response works, you will probably do it again until the behavior is learned (wired), if it doesn't work, you try something else.

You can teach a vacuum to do this on a trivial level. You just need basic functions defined. There is no mystery in regards to this, the brain is probably similar. It is not the hardware that enables the vacuum to learn, it is the software.

I think a major shortcoming of the mapping approach is that you are only looking at the hardware. Who cares how it is wired? Look at the DNA to see what sort of software the computer is running.

[Zarathustra]

Well in my opinion, I personally think consciousness can be pretty well understood with the right definitions.

For me, "consciousness" is the ability to recognize and adapt to the environment. When a child is born, their brain already has a bunch of circuits hardwired. These enable the organism to survive, but I do not believe they enable consciousness (at least not on higher levels). This being said, only those circuits which exhibit plasticity IMO are capable of conscious processes.

We already have a descent idea of how the brain accomplishes this. Plasticity occurs when you have repeated depolarization. So basically you are faced with a stimulus, you respond, and if the response works, you will probably do it again until the behavior is learned (wired), if it doesn't work, you try something else.

You can teach a vacuum to do this on a trivial level. You just need basic functions defined. There is no mystery in regards to this, the brain is probably similar. It is not the hardware that enables the vacuum to learn, it is the software.

I think a major shortcoming of the mapping approach is that you are only looking at the hardware. Who cares how it is wired? Look at the DNA to see what sort of software the computer is running.

To find the right definitons for our understanding of what conciousness is, is quite a hard problem, that of course doesn`t only refer to the hardware, the wired connections(?), but also to a flexible, dynamic, synergetic "software" the DNA. The synapses and the DNA recognizes and adopt to the enviroment. Although it`s hardly understood how synaptic connections, circuits or collums can do that, get weaker or more plastic, but how does it the DNA?? To measure epigenetic changes in vivo, how can you create paradigmas to try this?

In my point of view the circuits of a newborn maybe don`t give the ability to be conscious about something, but it offers the opportunity to become concious, and when should we differ between these two states, where are the borders?
Alva Noë says we need a confirmed habit about something. A child developes in the same time a sense of a self (the Frontal Lobe trained by the feedback of the environment), when the beginning of beeing conscious is supposed.

Consequently you maybe can teach a vaccum( what do you mean exactly with vaccum in that kind of manner, an artificial network?) to associate two things but to integrate it in a personal reflection, would need not only a software.

Plasticity, maybe the ability to reconnect something learned in a greater contrast or with another function, enables a higher level of integrity about something, but is it not also very less understood? Maybe there are circuits which gain this function to exhibit(IMO, never heard), but what is with the normal process of cell dying from apoptosis, necrosis. The effectivness of a circuit is not defined by the number or strength of connections and so propably not by the level plasticity.

[Flex]

It seems to me like the mechanism of plasticity is pretty well classified. Repeated depolarization causes mitochondrial migration, and you get a change in the ratio of quinones, which is indicative of a change in metabolism. These depolarization events are in my opinion one of the keys to understanding the mind-body phenomenon. I believe ion channel are a major key to how we perceive the world, and adapt.

It seems like most people forget about stretch gated ion channels after general bio. These receptors were first discovered in skeletal muscle, and are the basis for the transmission of nerve impulses from skeletal muscle. Ion channel proteins respond to changes in ATP. This means that there should be some local effect on kinases. One does not necessarily have to look at the brain directly.

What I mean to say is that perhaps the body is as conscious as the mind. Neuroscience tends to deal with voltage gated ion channels. Why not look to ligand gated channels etc. By stimulating these remote channels, I believe much about the mind and body will be learned.

[Flex]

http://www.cell.com/retrieve/pii/S0092867404010451

[Flex]

Example of body expressing consciousness (adapting to environment).

http://ajpendo.physiology.org/content/281/6/E1340.short

[Flex]

Proteomic will play a key role. As well as mapping neurons, mapping protein expression will be critical.

http://www.mcponline.org/content/4/3/278.full

[Flex]

Lipid profiles also have a huge signaling role http://onlinelibrary.wiley.com/doi/10.1002/mas.20023/pdf

The lipids contribution to consciousness is often neglected. Clearly then too, diet must be taken into consideration, as diet directly alter expression of all of the various omics.

Probably wont be a very pretty answer. If consciousness is defined as responding and adapting to the environment, then the interaction really needs to be looked at, not just the hardware.

[Flex]

Endogenous antioxidant synthesis: http://www.ajcn.org/content/81/1/277S.short

***Important for neurodegenerative diseases

[Zarathustra]

It seems to me like the mechanism of plasticity is pretty well classified. Repeated depolarization causes mitochondrial migration, and you get a change in the ratio of quinones, which is indicative of a change in metabolism. These depolarization events are in my opinion one of the keys to understanding the mind-body phenomenon. I believe ion channel are a major key to how we perceive the world, and adapt.

It seems like most people forget about stretch gated ion channels after general bio. These receptors were first discovered in skeletal muscle, and are the basis for the transmission of nerve impulses from skeletal muscle. Ion channel proteins respond to changes in ATP. This means that there should be some local effect on kinases. One does not necessarily have to look at the brain directly.

What I mean to say is that perhaps the body is as conscious as the mind. Neuroscience tends to deal with voltage gated ion channels. Why not look to ligand gated channels etc. By stimulating these remote channels, I believe much about the mind and body will be learned.

Sure the effects of depolarization and the regulatory abilities of a cell is quite interesting, ion channels play a major role in that kind of manner. But focus too much on the this aspect is like buying a ticket but not going in the stadium. The basic molecular events in and around ion channels, in my point of view, can be examined in other cells too, when the same resources of signal transduction machinery is given, the same ability too integrate them to an transduction-impluse, etc.. But the easiest way would be to use a similar networks or cells (aplysia, fruit fly) with the same receptor-configuration .

How I understand that much research is going on referring to ligand gated channels. The psychopharmacy is interested in that, because you can directly provoke changes in Neurotransmitter systems and have huge effects. But the hole story is also lacking, to change one system effect the ballance, the homoestasis is so important, also when there is a disease. Additionally the work about neuropeptides and their diffuse distrubution will maybe drive that into another direction and enable an deeper more ballanced effect of neurodrugs.
Voltage gated are worse understood, even though they are the majority in the brain. For example the rhythm of the brain ( alpha, beta, gamma waves) control the state of consciousness, is someone is sleepy, awake, in a illisionary state, etc. In my meaning they have a major position in a neuronal network.

The body has a consciouness, of course, when you define to be conscious like to perceive and to adopt, then even a single cell, ya even a protein is that, but where is the meaning? Has a body a reason to be conscious without the mind? Would the body perceive anything when there would be not a representation in the brain? Cells need also a reflection to a goal to act to receive and adopt with sense, and a feedback system that gives him a sense of direction. For example, a patient with a ghost limp feels his lost leg over month or years, the upper motory system adopt to his ghost limp movements, but because the feedback of the brain is still there. A anxiously person gets a higher blood pressure if you confront himwith a feard stimulus, but when you give him beta-blocker, he maybe start to shiver. When you would inhibit the amygdala, EVERY reaction reffering to fear would be inhibited.

[Flex]

The brain to me is no more conscious that the rest of the body. Sure it may be the central hub of our awareness, but as far as the functionality of the body is concerned, I am less convinced. It is just like a bee hive. No one bee is conscious of the whole, each unit is only aware of its direct surroundings, yet the colony functions as a single entity. With enough individual proximal connections, you can build a network of awareness, which is much more encompassing and dynamic.

[Yoder]

The brain to me is no more conscious that the rest of the body. Sure it may be the central hub of our awareness, but as far as the functionality of the body is concerned, I am less convinced. It is just like a bee hive. No one bee is conscious of the whole, each unit is only aware of its direct surroundings, yet the colony functions as a single entity. With enough individual proximal connections, you can build a network of awareness, which is much more encompassing and dynamic.

I like this.. Great analogy, Flex!

[Flex]

http://www.tedmed.com/videos-info?name=Dea...pdated&year=all

[Zarathustra]

The brain to me is no more conscious that the rest of the body. Sure it may be the central hub of our awareness, but as far as the functionality of the body is concerned, I am less convinced. It is just like a bee hive. No one bee is conscious of the whole, each unit is only aware of its direct surroundings, yet the colony functions as a single entity. With enough individual proximal connections, you can build a network of awareness, which is much more encompassing and dynamic.

Nice metaphor, I have heard about this before, I don`t know who said it, but I like it. Trying to grasp the very complex ongoing processes with an simple explaination like this is always something what explain a complex structure very simple. And the most delightful discoveries are simple to explain, right? Like the quote: "the memory is the clue which binds our mental life together"
The difference to yours is that this quote is not missing the core of the problem.
When you think of entities your explaination is right, the single bee gives, while working in a colony, the hive a higher function and therefore entity. Therefore to find the core-problem of awareness and its dynamic encompassing entity we should just find the different bees (the fuctional different cell types) with its functional behavior and we would easily have an idea how the clue is made of whch binds our awareness together. It`s a pity, that there are a couple of phenomenons out there which give the hole a different direction. But ok these phenomenons are the interesting aspect, and just with them you get the "hive" you have wit the human conciousness. The interaction of information systems like the nerve cell and a immune cell, the different factors which covers information like Neurotransmitters, Neuropeptides, Zytokines, Brain-wave-rhythms, Frequences of actions potentials, DNA-methylation and so on. Or the different ability to cover information for a controlled time like new synapse contacts, memory T-cells, pacemakers cells etc.. The conscious of body control is f.e. stored in pacemaker cells or defined neural circuits in proper brin areas. f.e. the hypothalamus, which controls the hormon status through complex feedback loops, controls the temperature and the day night rhythm (together with the epiphysis). Other very basic funtions are stored in other brain areas, in conserved nerve circuits. Without them the body had not the chance to regulate and be aware of its own at all. For me the body can just be concious about itself with the brain, the brain with its acting of thinking etc. the spirit, dont need the body.

Greetings





P.S.: Sorry for my late answer, the turned off the internet for a while in dorm.