23 replies to this topic

[Lazarus Long]

I am going to start this topic and ask for all participants to expect to use the targeted organ to its limits. [huh]

We know, and I use the word in its most FACTUAL Sense that there exists a relationship of Brain and Mind.

So, define it?

We must examine the biology of the brain as both a living mechanism and make a qualitative examination of the function itself, the "organ's role in the body."

Simply put this is How and Why the brain does What it does.

So we know there are neurochemical transmittors and receptors, we see bioelectric current conducted through to synaptic relays, sub-sensor input/regulator functions, and so much more; we see everything except who we are in the puzzle.

By we, I mean that elusive quality of experience as it even transcends memory, into
"I think therefore I am" awareness.

So HOW is the brain doing this?

Why does the biology of the Brain function this way?

What is the hardware and what is the software of this phenomenological thinking organ/machine [?]

Penrose may not be a biologist but he is a powerful thinker. He is saying that from a mathematicians perspective the quality and complexity described by neural function is thematically equivalent with what a physicist would call a quantum computational device.

This from the simple calculation of sumerizing all the functions and simultaneous complex processes being handled both cognitively and subcognitively simultaneously.

So to all I say the simple challenge of prove him wrong.

I am looking at this a little differently as well.

I am looking at an "integrated system" which evolved out of more primitive less coherent multiple systems of symbiotic life forms (different species), that have created a coherent (singular) collective conscious for mutual identification and life support. A sort of integrated Evolutionary Biology and Psychology.

Prove me wrong too [!]

And lets have some fun at it, let the games begin [!]

[ocsrazor]

Hi Lazarus,

These are some HUGE questions you are asking but ones I think about all day long. This is the most complex system that humanity has ever tried to comprehend So where do you want to start? Top-Down or bottom-up? Behavior or ions? I can tell you what we know from the biology.

Unfortunately I am off to a conference this week so I probably won't be able to contribute too much until next Monday, but I would love to bounce ideas around in here.

As a quick reaction to the Penrose quantum brain argument (I haven't looked at his stuff in a while and I didn't read the second book) but what I remember is his mathematics have some fundamental quantitative assumptions that are incorrect based on the biology, there is no evidence for the biological mechanism he suggested for quantum computation, his quantum physics are off because of temperature considerations, and (most important for me) the brain just doesn't do as much computation as he assumes it does. Each of these is a long explanation in itself and I will have to reinstall this stuff in my memory by looking back through some old notes, so be patient [blush]

Best,
Ocsrazor

[Aegist]

I'm having trouble figuring out exactly how evolution and biochemistry have worked together to create subjectivity atm. That is my greatest challenge. It is easy to talk about causes and reactions. But figuring out how seeing is experienced, and how warmth is felt etc is a lot harder.

Subjectivity just doesn't make sense in an Objective universe.

[Lazarus Long]

Relativity not Subjectivity,

Objectivity is subject to Relativity.

[kevin]

Here goes.. Penrose notwithstanding.. or rather left outstanding as I don't know ANYTHING about him, I'm sorry to say.

The nature of the relationship of brain to mind.

It occurs to me that an attempt to define the nature of the mind/brain relationship in humans, relative to that of more primitive organisms, could be set in the context of evolution and the advantage that having a superior 'mind' has given our species over our less 'evolved' bretheren.

I don't have much in the way of proof to the contrary but I don't believe that conciousness arose from the integration and cooperation of identifiable primitive systems of multiple life forms. I do believe that multicellular life arose from the cooperation of unicellular life. ie. mitochondria were once photosynthetic bacteria living inside other and that in order to perpetuate their genetic code organisms from different species may have merged their DNA in a cooperative structure. I think it more likely that this cooperation gave rise to structures/lifeforms who contained within them, the full set of 'hard coded instructions' for survival and that 'instincts', came long before consciousness where consciousness is an awareness of "I". I believe that awareness of self came quite late in evolutionary terms and is a natural outcome of the modification of survival program that allows more flexibility to adapt and pass on the more 'sentient' organisms code.

To examine further how the sense of "I" might have been a benefit over instinct we can look at how its' operation might influence survival.

In order to experience "I" there has to be a "other" that is "not I" to which it can reference itself, the external world, a source of threat and opportunity. Does a heightened sense of "I" increase the recognition of possible threats to its' survival from the "other"? Does a heightened sense of "I", allowing greater discernment of "other", lead to more data points which allows better interpetations by the basic survival program of "other", for opportunities that maximize survival? What relationship might other attributes related to the experience of "I", such as feelings and reasoning have to the experience of "I"?

It seems that the force which drives 'lifes code', (currently in the form of DNA/RNA), has managed to create a viable pattern for survival by creating various levels of biocomputers. The more complicated ones (us among them) seem to have reduced hard coding (instinct) with a concommitant increase in adaptability brought on by an increased sense of "I", although providing the "I" with enough information on which to operate takes a LOT longer. Any parent would probably agree that a baby is self aware from the moment it takes its' first breath and probably before. The increased sense of "I" is intrinsic to the operation of the biocomputer. The "I" itself, must be hard coded, much as instincts or the ability to see is, into the neural pathways of the brain and does not arise as result of experience, although without inputs, the program would have no data to work with and remain undeveloped, much like children who are slower to learn as a result of an impairment to one or more of their senses.

As everything I've read on the discoveries of how the brain works seems to indicate that specific areas are used for specific functions, I might suppose that the program for the ability to experience "I" is also stored in a very specific manner.

Therefore maybe it is possible that the "I" is an upgrade to hard coded instincts, and forms one of the higher levels of the 'kernel' of the operating system of the biocomputer that is our brain, and that it can probably be pinpointed in physical location. It may operate like a CPU does by using hardcoded operation instructions to interpet and route incoming data from various inputs.

This may be taking the computer analogy a bit far... but it does make some kind of sense.

This doesn't actually speak to the question of what "I" actually is, but it seems to me that if you have a hard coded structural program running and accepting inputs 24/7, awareness of the "I" results from the interpetation of incoming data itself and is intrinsically a consequence of the operation of the program. Can there be an interpetation of incoming data without an awareness of "I"? I would have to say yes, but then I would call it instinct or hard coded programming which has narrower parameters and reduced flexibility, and thus reduced viability, in a changing environment. If the environment didn't change, or changed VERY slowly, there would be no pressure to have a more flexible system.

I believe that the sense of "I", is the genetic codes way of creating an adaptable structure with enhanced abilities to create an environment conducive to its' perpetuation. It also seems to me that being able to experience "I" is primary. Other attributes of the mind such as feelings, intelligence (as defined by the ability to reason), etc, are built upon the "I' program and cease if the "I" program stops running as evidenced by the number of diseases of the brain where the final program to go is always(?) an awareness of self. There is no longer anything for those processes to refer to, there nothing that "feels" or "thinks". It would seem understandable as well then, that organisms with a less developed "mind" or lower levels of concisouness, would have a lower capapcity for reasoning and feeling as these are higher functions of more complex biocomputers.

You're right Lazarus.. that was fun..

Please feel quite comfortable in pointing out the gaping holes in my reasoning and information... I look forward to learning more by watching the discussions..

K

Edited by kperrott, 04 March 2003 - 05:27 PM.

[Psychodelirium]

Penrose may not be a biologist but he is a powerful thinker.  He is saying that from a mathematicians perspective the quality and complexity described by neural function is thematically equivalent with what a physicist would call a quantum computational device.  

This from the simple calculation of sumerizing all the functions and simultaneous complex processes being handled both cognitively and subcognitively simultaneously.  

So to all I say the simple challenge of prove him wrong.

Just a quick remark for the moment:

You are unjustly shifting the burden of proof. It is not up to us to prove Penrose wrong; it is up to Penrose to prove Penrose right. And so far, he hasn't been doing a very good job. In fact, I am not aware of any evidence that our brains are quantum gravity computers of the sort that Penrose imagines - the only reason he gives us to believe that they are is his unsound argument for the noncomputability of minds from Godel's theorem.

[Lazarus Long]

I didn't shift the burden of proof unfairly at all, clearly he has to prove his claims as you are attempting to disprove them. I frankly don't claim to be in accord with Penrose, other than we might agree that the brain is a functioning Quantum Computer. Now let us define even that, actually under CIRA guidelines that constitutes a separate thread.

Penrose is not a biologist that is for certain and I am not taking his argument as my own, and as I alluded to I see the issue differently. I did however define questions that are significantly larger in scope and require a detail of understanding greater than the arguments made by Penrose.

Please if you are dissatisfied with Penrose's agrument feel free to expose all manner of fallacy he is subject to, and subjects us to.

But from there please let us go forward and seek answers too. The questions I posited are:

We know, and I use the word in its most FACTUAL Sense that there exists a relationship of Brain and Mind.

So, define it?

We must examine the biology of the brain as both a living mechanism and make a qualitative examination of the function itself, the "organ's role in the body."

Simply put this is How and Why the brain does What it does.

So we know there are neurochemical transmittors and receptors, we see bioelectric current conducted through to synaptic relays, sub-sensor input/regulator functions, and so much more; we see everything except who we are in the puzzle.

By we, I mean that elusive quality of experience as it even transcends memory, into
"I think therefore I am" awareness.

So HOW is the brain doing this?

Why does the biology of the Brain function this way?

What is the hardware and what is the software of this phenomenological thinking organ/machine [?]  

[kevin]

Great topic.. I have a little more insight now into the quantum computer model of conciousness but not enough to add to the discussion.

For those interested, here's a link to a general description I found informative.

http://www.conscious...rink/brink.html

Edited by kperrott, 04 March 2003 - 10:16 PM.

[acaveyogi]

The relationship between the mind and the brain. It is interesting Lazarus that you separate the two. The mind actually exists in the DNA computer. It takes several billion of these little buggers to generate enough noise to run a body.

The DNA computer communicates internally with itself and with other close by DNA computers with minute RF signals. These signals have different frequencies for different tasks.

In a healthy body all DNA computers are at one with each other and are working as a single unit to solve the physical and mental challenges of life as a living body.

The function of the brain is to amplify these minute RF signals and then translate them in physical movement and/or bio-chemical phenomenon. And this is why science will never figure out how the brain works as a computer because it doesn't, it is an amplifier.

The reason that a strand of DNA or RNA just all of a sudden becomes active and starts to produce something is because that strand has received a minute RF signal that is the same frequency that that strand is tuned to respond to.

In closing, when science starts to build a computer that communicates with itself using minute RF signals or light, Then you are going to see a machine that can out compete man. And the reason for this is because it won't get sidetracked. Love, john

[Lazarus Long]

The relationship between the mind and the brain. It is interesting Lazarus that you separate the two. The mind actually exists in the DNA computer. It takes several billion of these little buggers to generate enough noise to run a body.

I am not actually separating them. I am distinguishing between the physical characteristics and the (for lack of a better descriptive term) Non-Physical aspects.

As for the physical chracteristics, the Brain maintains BOTH singular concentrated cognitive ability, culminating in the evolution of the Cerbral Cortex and counterposed to this a vast array of subprocessing ability that extends throughout the body into the diffuse, almost notochordal function's of the ganglia and limbic system.

I find the fact that the cerbral cortex is denied direct command function over these as very interesting and not just a simple coincidence of evolution. True it is more effecient, and we can hold our breath for a few minutes but we can't hold our breath till it kills us.

Yes, a well disciplined yogi (and others) can slow and almost stop their heart but why does it require such discipline and study?

Clearly evolution has placed barriers in our way for such behavior. The cognitive command processes of the Operating System we identify with does not easilly override the command functions of the basic primary comand systems of the Life Support involved in Body Maintenance.

Whether we will come to all agree that this computer called a brain is a quantum one we can all agree I hope that you are correct in saying it is definitely a DNA Computer.

In closing, when science starts to build a computer that communicates with itself using minute RF signals or light, Then you are going to see a machine that can out compete man. And the reason for this is because it won't get sidetracked.

This is already happening and why this discussion parallels the one on Artificial Intelligence and the Singularity.

[acaveyogi]

Lazarus you are awesome I love your mind Anyone else would have questioned my source of information but not you. Instead you explain to me that I am not on the same subject that you are. I love it! Again Do you want a meditation that will shut down your nervous system and kill you? Nature has a way to allow animals (including people) who are unhappy or experiencing trauma (mental or physical) out of life. I think it is Natures way of being humane. Anyway I have no idea what the subject of this topic is, so with no further ado I shall humbly remove myself from this discussion. Love, john

[Lazarus Long]

Do you want a meditation that will shut down your nervous system and kill you? Nature has a way to allow animals (including people) who are unhappy or experiencing trauma (mental or physical) out of life.

Have I offended you in some manner that you would offer to have me kill myself?

I thank you for your compliments with regard to the subtleties of my thought process but I must graciously refuse your offer. I am not yet ready for knowledge of such a technique as I couldn't resist the temptation of challenging its limits.

I can understand it existing however and was alluding to the concept of being able to control all physical systems through mental discipline. It doesn't require a "rocket scientist" to appreciate which groups have devoted the most study into this area of expertise.

Please stay with us but I do insist we stay closer to the topic in question for this thread. I might suggest however that we are sorely lacking in the Eastern perspective of Cognitive Theory and you being more expert in that realm, might act as a guide for that study in another thread.

Later as the two threads of Eastern and Western thought develop sufficiently perhaps we could then again return for a comparative study.

[acaveyogi]

Hey Lasarus, I think I have figured out what the subject is! You are saying that there is no real proof that the mind can affect the brain. And I guess that I am saying that there is

The drawback is that you would have to test it on yourself to see if it is real. This can be tested safely as long as you are not a depressed person. The first symptom is constriction of the throat; The second symptom gass pressure in the stomach and intestinal track; The third symptom is lung congestion; The fourth symptom is absolute panic; The fifth symptom is chest pain. And so on.

Sometimes animals and people who are unhappy or bored with life, will stimulate this area in a flirting way. This shuts down the immune system and over time (sometimes short) they die of disease or cancer or both.

You guys don't think that I would investigate physical immortality with out being able to reverse the process do you? I don't want to live for eight hundred years. I am only doing this because there are people who do and to see if myth was right. Love, john

[Lazarus Long]

Hey Lasarus, I think I have figured out what the subject is! You are saying that there is no real proof that the mind can affect the brain. And I guess that I am saying that there is

Precisely incorrect.

I am saying that the mind DOES effect the brain and we do influence it all the time UNKNOWINGLY, for example, in the way hormones are released through stress.

I am asking that we scrutinize the mind body relationship more closely and define it better in terms that are more universally understood. Clearly I do feel we need more constructive knowledge on this subject, NOT that I have an "a priori" axe I want to grind.

I suggested above that you consider guiding our pursuit in the field you understand best for this and descrbe the specifics, for example of meditative technique. Not just an overview but sharing specific methodologies with precise goals, parameters, and risks outlined in advance. I am only saying that for the present the discussion doesn't really belong under this thread, it is certainly a relevant parallel discussion however.

[acaveyogi]

Ok Correct me if I am wrong: What you are saying is that I am still not understanding the subject. But, I am possibly close enough to at least create a reality that would make a relevant parallel discussion at some other time. So ok here goes:

Nature has created a system in the autonomic nervous system that takes unhappy animals and people out of life. Everytime that an animal or person is unhappy for any reason (real or imagined) the subconsious mind activates this system (system D). Everytime system D is activated it causes deterioration of the physical body and this deterioration is accumulative. We recognize this deterioration as weakening of the immune system and as the aging process.

When systen D is activated there is tension created in the medulla complex. If this tension is extreme the entire autonomic nervous system shuts down. If the tension is not extreme then just the pituitary gland (master life gland) shuts down, which in turn shuts down the thymus gland (immune system). These temporary shutdowns cause damage to the physical body that accumulate over time.

Now advanced yogic science teaches that the mind is a thought generator and that the body is a thought activated gismo. The problem is that the mind is controlled by our personality programing and when our programing decides that for what ever reason, real or unreal, that we are unhappy, then unbeknowance to us system D is automatically activated.

Traditional yoga trys to solve the problem by changing your personality so that your personality controls your mind in a healthy way. This takes years, if ever. So I dumped that concept and studied how to bypass the personality and stimulate the life center and immune system (and a bunch of other things in my body and the bodies of others) directly with the consious mind.

Science is studying the mind brain/body relationship from the outside, I have studied the mind brain/body relationship from the inside. I feel that if there was a way that I could compare notes with science, in the laboratory, that science could find a way to extend your guys life spand in a significant way without you guys having to become advanced yoga masters.

So my question to the group mind is: Does anybody know of an organization that is turely interested in solving the "physical immortality" question? And if you do how do I contact them?

Thank you lazarus for allowing me to disrupt the train of your discussion. I am sure that BJ will stick this some where where it is appropriate. Love, john

[Lazarus Long]

Nature has created a system in the autonomic nervous system that takes unhappy animals and people out of life. Everytime that an animal or person is unhappy for any reason (real or imagined) the subconsious mind activates this system (system D). Everytime system D is activated it causes deterioration of the physical body and this deterioration is accumulative. We recognize this deterioration as weakening of the immune system and as the aging process.

Why is an animal unhappy if its needs are met?

If it is in physical pain then this is a physical ailment already and not generate by the "emotion of unhappiness". If it is a social animal is it unhappiness caused by the "society" (a social dependence) , or are you referring to the kind of "unhappiness" we see in people with imbalanced neurotransmitter levels?

I understand what you are claiming about how the system is affected by HOW you think but I am asking you to address why it does this, and the specific mechanism. Also a more precise and less hypothetical example of HOW the Mind influences the brain, and subsequently the body.

Unhappiness versus happiness is an old standard (the classic Aristotelian measure) and I have seen that clearly unhappiness accelerates aging; this is common.

What I think is more germane to the topic is specifically how happiness counters the process. Also how do you address legitimate cause for unhappiness without becoming superficial and just ignoring everyone's unhappiness if you are empathic and their grief causes harm by generating unhappiness for you?

[acaveyogi]

Let see, ok, Lets define unhappy: "Unhappy is any and all things that could possibily be construed as unhappiness." The reason for being unhappy is irrelevant. And the greater the degree or intensity of unhappy the quicker things happen.

What makes system D so insidious is that it is built into the autonomic nervous system just like breathing, heart beat, and digestion. So if it is there, then why is it there?

Lasarus if I can explain this to you then I can explain this to science. You are science. We have two hurdles to over come: One is that we do not speak the same language and Two is that we do not exist in the same philosophical reality.

Scientifically speaking there is no reason why system D should exist. That is a given. I can prove in a lab that what I am saying is real. You put me in a MIR and I will turn things on and off in my brain from the inside so that you can see it on a screen. And I can give you a meditation that will allow you to stimulate or bring on line system D.

So with all that said here we go In Nature survival of the fittest is the law. Realitive to creachers with advanced nervous systems how does Nature know when a creature is no longer fit? The creature becomes unhappy in some sense of the word.

obviously not fit:
Lets say that you are grabbed by a Tyranosourus and experience body sever body tramma but are not dead. The mind kicks in system D and system D shuts down your entire autonomic nervous system, you go into a state of bliss and die. This is Nature's way of being humane.

not so obviously not fit (this is what is getting mankind):
As long as a creature is competing successfully in nature it is happy, it is winning. The pituitary is on, the thymus is on and nature says that individual is fit. The instant that that individual feels unhappy for any reason (even boredom) Nature starts to take that individual out. Nature's tools are disease, other animals, and deteratioration of the body. This process is started by system D shutting down the pituitay and the thymus automatically each time the individual experiences "unhappy".

Ok, I figured let's just stimulate the pituitary and the thymus and this should solve the problem. Well, what I discovered was, "not exactly". It stopped the deteratioration and is kept the disease stuff at bay, but it did not repair the damage that we call aging.

What is interesting is that the "physical immortallity" meditations seem to be repairing the damage that we call aging as well as well as stopping the damage. I have no idea why. I think that science has gotten to the point that they could take a picture of my brain while I am doing the meditation an see just exactly what is going on. I can teach this to others but they have to be physically in my presents on a one to one bases. I don't have the facilities. Well Lazarus now how can I translate this into your language. Love, john

[Lazarus Long]

Well Lazarus now how can I translate this into your language

This is unnecessary too.

Just attempt to express yourself in "your" language and I will try to understand what you do and how you do it by how you express such an awareness.

[acaveyogi]

Thanks Lasarus for interacting with me. That was pretty much all I had to say. And as I told BJ I am not really here to teach yogic science. Below is one of the simpler physical immortality meditations if anyone would like to give it a try:

Feel the gentle warmth and see the golden light of the morning sun in the area between your slightly raised eyebrows ( Do Not actually look at the sun!). Then allow the golden body of Life (or God) to exist within your complete body. Then feel the bottoms of your feet.

If you are doing this right it should make you sleepy or very relaxed. This is because it puts you into a state of alpha consciousness for a moment. It is best if you do this meditation lying down or sitting down to start with. If you do this meditation very much you will begin to notice that look and feel younger and that you have a glow about you. And others will notice this change too.

Will, I am off to continue my internet journeys, thanks for letting me visit. Love, yogajohn

[Lazarus Long]

Before I come back to comment on the Mind/Brain interface that Acaveyogi was addressing I want to post an article from last month's Journal of Neuroscience. The relevance should be obvious as it addresses what is undoubtably at least one aspect of age onset senescence and perhaps the most common and inevitable one.

As I don't have access to the full text anyone who does I would be curious what the study suggests as to what are the mechanisms of the "shrinkage" and why is the processing occurring?

Metabolic assimilation of dying tissue for elimination from the body perhaps as a response to cumulative damage?

The Journal of Neuroscience, April 15, 2003, 23(8):3295
http://www.jneurosci...tract/23/8/3295

Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain
{abstract}
Susan M. Resnick1, Dzung L. Pham1, Michael A. Kraut2, Alan B. Zonderman1, and Christos Davatzikos2

1 National Institute on Aging, Baltimore, Maryland 21224-6825, and 2 Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21287

Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults.

Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 ± 0.3, 2.4 ± 0.4, and 3.1 ± 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 ± 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline.

Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults.

These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy.

Key words: magnetic resonance imaging; aging; brain volumes; longitudinal studies; gray matter loss; white matter loss

Full Text of this Article

Reprint (PDF) Version of this Article

Edited by Lazarus Long, 01 June 2003 - 06:47 PM.

[Lazarus Long]

I am going to put this here for now.

These two articles really belongs in their own thread but I want to nudge Peter (and invite Anders to the debate PLEASE!!! Along with Aubrey and Rafal) to come back to this issue because it addresses some recent findings on neuron regeneration and the techniques that are being developed which discovered phenomenon that appear to contradict long held theories on neurophysiology.

Here is an interesting article for example that describes how synaptic response functions and how our concept of it is metamorphosing almost as fast as our synapses can assimilate the data. )

Nature Reviews Neuroscience 4, 520 (2003); doi:10.1038/nrn1157
Weblink to Original Article
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[2291K]

SYNAPTIC PHYSIOLOGY
Kiss-me-quick synapses

Rachel Jones

Wouldn't it be easier to extract the secrets of the synapse if we could see what is going on there?

For example, if we could just watch a synaptic vesicle fusing with the membrane and then being recycled, we could finally answer some of the questions about how the recycling is accomplished.

Two papers in Nature use fluorescent markers to achieve just that, and reach complementary conclusions about vesicle recycling at small synapses.

Our understanding of synaptic exocytosis — the process by which individual vesicles fuse with the cell membrane and release their loads of neurotransmitter into the synaptic cleft — has come on in leaps and bounds over recent years. But what happens next is more of a mystery.

It is generally thought that most vesicles collapse into the presynaptic membrane before their components are retrieved, but another school of thought suggests that some vesicles do not collapse; instead, they fuse transiently with the membrane and open a fusion pore, before closing the pore and being recycled as a unit. This mechanism, which is called 'kiss-and-run' exocytosis, receives strong support from the two new papers.

In the first study, Gandhi and Stevens infected hippocampal neurons with a virus carrying the gene for synaptophluorin — a pH-sensitive marker that fluoresces when the inside of a vesicle is exposed to the external medium.

When a cultured neuron is stimulated, the fluorescence rises as vesicles fuse with the membrane and then falls back as they are endocytosed. By studying the time course of these events, the authors were able to show that vesicles undergo three distinct types of exocytosis. In the first, which Gandhi and Stevens specifically call kiss-and-run, vesicles are recycled quickly (in less than a second) and the fusion pore that opens is selective — for example, the buffer Tris can enter the vesicles but another buffer, HEPES, cannot.

The second type of fusion was slower, with vesicles being recycled after 8–21 seconds, and is termed 'compensatory' endocytosis. In the third, 'stranded' vesicles seem to remain fused with the membrane for more than 45 seconds, although it seems that their endocytosis can be triggered by subsequent action potentials.

Aravanis et al. used a different technique, in which vesicle membranes are labelled with a fluorescent dye (FM1-43) that is released when exocytosis is stimulated in dye-free medium. The drop in fluorescence can be seen when exocytosis is triggered by stimulation of cultured neurons.

Most vesicles lost only part of their fluorescence when they fused with the membrane, supporting the idea that they released the dye through kiss-and-run exocytosis rather than by complete collapse into the cell membrane. And, as pointed out by Rizzoli and Betz in an accompanying News and Views article, the time-course of dye release indicates that these fusion events correspond to the 'compensatory' endocytosis described by Gandhi and Stevens, rather than to their very fast kiss-and-run events.

So these two studies provide compelling evidence that most vesicles in small hippocampal synapses fuse by a kiss-and-run type of exocytosis, rather than by collapsing into the presynaptic membrane.

This finding contrasts with previous studies showing that vesicles collapse before being recycled slowly; but many of the earlier studies used different types of synapses with large numbers of vesicles. The techniques used in these two papers should allow future work to resolve such discrepancies, and to look deeper into the mechanisms and control of synaptic recycling.


References and links

ORIGINAL RESEARCH PAPERS

Gandhi, S. P. & Stevens, C. F. Three modes of synaptic vesicular recycling revealed by single-vesicle imaging. Nature 423, 607-613 (2003) | Article | PubMed | ChemPort |

Aravanis, A. M. et al. Single synaptic vesicles fusing transiently and successively without loss of identity. Nature 423, 643-647 (2003)
| Article | PubMed | ChemPort |


FURTHER READING

Rizzoli, S. O. & Betz, W. J. All change at the synapse. Nature 423, 591-592 (2003) | Article | PubMed | ChemPort |

Rizo, J. & Südhof, T. C. SNARES and Munc18 in synaptic vesicle fusion. Nature Rev. Neurosci. 3, 641-653 (2002) | Article | PubMed | ChemPort |

Nature Reviews Neuroscience 4, 522 (2003); doi:10.1038/nrn1161
http://www.nature.co...ml&filetype=pdf

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DEVELOPMENT
Slinging out old theories

Heather Wood

The glial sling — a transient bridge-like structure that spans the septum of the developing mammalian forebrain — is something of an enigma. Since it was discovered in the early 1980s, it has been assumed to consist of glioblasts, which were thought to provide a guidance substrate for the axons of the corpus callosum.

However, because of a lack of suitable molecular markers, this idea was never corroborated. Now, as reported in Development, Shu and colleagues have revisited the glial sling in the mouse, using the array of markers that has since become available, and they present compelling evidence that it actually consists of migratory neurons.

Shu et al. found that the sling did not stain positive for commonly used glial markers such as GFAP, RC2 or GLAST. Markers for mature neurons, such as neurofilament, were also absent. However, the sling did express the early neuronal markers NeuN and TUJ1, indicating that the cells were most likely to be immature neurons.

The sling cells also showed electrophysiological activity that was consistent with an early neuronal identity, including spikes that resembled Na+- and Ca2+-mediated action potentials. By filling the cells with the tracer biocytin, the authors showed that they had a neuronal morphology, with a long leading process and shorter processes that resembled dendrites.

Most of the neurons in the sling seem to originate from the cortical subventricular zone (SVZ), although Shu et al. also found evidence of cell proliferation within the sling itself. Interestingly, in spite of this proliferation, and the presumed continuous replenishment from the SVZ, the sling does not increase significantly in size during development. On the contrary, it begins to shrink after birth, and it is undetectable by postnatal day 10.

The ultimate fate of the sling cells remains a mystery. It was previously thought that they underwent programmed cell death. However, although Shu et al. identified a few apoptotic cells in the sling just before birth, the extent of cell death was insufficient to account for its disappearance.

The authors therefore make the tantalizing suggestion that the sling neurons might survive and migrate to other regions of the brain. The question of where the cells go, and what contribution, if any, they make to the adult brain, should provide ample scope for future study.


References and links

ORIGINAL RESEARCH PAPER
Shu, T. et al. The glial sling is a migratory population of developing neurons. Development 130, 2929-2937 (2003) | Article | PubMed |


FURTHER READING
Silver, J. et al. Axonal guidance during development of the great cerebral commissures: descriptive and experimental studies, in vivo, of the role of preformed glial pathways. J. Comp. Neurol. 210, 10-29 (1982) | PubMed | ChemPort |

[Lazarus Long]

http://news.bbc.co.u...lth/3051496.stm
Brain clue to stress disorder
Saturday, 12 July, 2003, 23:56 GMT 00:56 UK

Some people may be more vulnerable to the effects of stress because an area of their brain is smaller than average.
Scientists have found an area of the brain called the anterior cingulate cortex is more likely to be small in people who have developed symptoms of post traumatic stress disorder (PTSD).

The anterior cingulate cortex is known to play a role in regulating emotion.

PTSD is a disturbing psychological condition where people who have lived through a stressful experience relive painful memories against their will.

This can lead to feelings of isolation and a sense of losing control - patients sometimes turn to alcohol or other drugs as they attempt to get rid of the flashbacks.

Previous studies linked PTSD to structural abnormalities in the brain - in particular in the hippocampus, an area involved in long-term memory.

However, these studies yielded inconsistent results, and few areas other than the hippocampus have been thoroughly investigated.

To determine if other brain regions are structurally affected by PTSD, a team led by Dr Hidenori Yamasue at the University of Tokyo used a recently developed technique known as voxel-based morphometry to study the whole brain.

The scientists recruited 25 survivors of the 1995 Tokyo sarin gas attacks, nine of which suffered from PTSD.

After performing brain scans, the researchers found that the left anterior cingulate cortex was significantly smaller in subjects with PTSD compared to those without the disease.

And the smaller it was, the greater the severity of PTSD symptoms.

Emotional regulation

No other significant differences in grey or white brain matter were found between the two groups

The scientists suggest that abnormalities in the anterior cingulate cortex may interfere with emotional regulation, in some cases increasing the chances of developing PTSD.

Simon Meyerson, a consultant psychologist and expert in PTSD, said the structure of the brain may be one factor in the development of PTSD.

But he said it was a complex condition, probably caused by many factors.

"PTSD is caused by a psychological blast to the mind, and it is the personality, not the physique that begins to crumble," he told BBC News Online.

"The physical nature of the brain may be one ingredient, but it is not likely to be a major factor. The structure of the personality - whether it is solid or fragmented - is likely to be more important, and that is governed by all sorts of things, including learning and social interaction."

The research is published in the journal Proceedings of the National Academy of Sciences.

[Lazarus Long]

A useful resource for laypersons and professionals alike. Go to the page for referenced links.
http://brancusi.usc.edu/bkms/

The Brain Architecture Management System


The Brain Architecture Management System (BAMS) is designed to be a repository of information about brain structures from different species, and has a set of inference engines for processing the neurobiological data. BAMS contains to date four interrelated modules: Brain Parts (brain regions, major fiber tracts, and ventricles), Cell Types, Relations (between structures from different neuroanatomical atlases), and Connections.
The system contains to date on the order of 10,000 reports of connections between different brain structures in the rat, as collated from the literature. Users can view projection patterns as reflected in the literature and as associated with records of brain structures inserted in the system. Users can also construct reports of connectivity matrices related to brain structures of interest.
BAMS contains neuroanatomical nomenclatures for the rat, human, macaque, cat, and mouse (more than 6000 names).

To start searching BAMS click on the "Menu" link in the left frame.

More information about BAMS and description of the "Menu" functionality is provided in the About section.

If you would like to set up an account in the system to insert data either in the public part of BAMS, or in the personal account, please contact the system administrator.

If you would like to receive updates about new features and tools added to BAMS, or when new data is inserted please go to the Registration page.

--------------------------------------------------------------------------------
Copyright 2002, University of Southern California

[Lazarus Long]

Researchers Compile 'Atlas' of the Brain
Fri Aug 8, 9:27 AM ET Science - Reuters
By Deena Beasley

LOS ANGELES (Reuters) - A computerized "atlas" of the brain is for the first time giving researchers and medical experts a map for unlocking the puzzles of the mind.

The 10-year project "was born out of frustration," said Dr. John Mazziotta, chair of the department of neurology at the University of California, Los Angeles, medical school. "Unfortunately, the brain is different in every single person. There is a tremendous amount of variance."

As a result, researchers and radiologists have essentially relied on their own experience to measure brain activity or diagnose disease.

But the atlas, which the researchers recently started making available for use, will allow specialists to compare a patient's brain with those in the data base. This may enable them to detect crucial differences in the brains of sick people and thus diagnose and treat them.

An international research consortium, led by Mazziotta and Dr. Arthur Toga, director of UCLA's laboratory of neuro imaging, has so far gathered digital images of 7,000 brains using technology such as magnetic resonance imaging scans (news - web sites). The scans taken of the brains of people mainly between the ages of 20 and 40 are colorized, animated and otherwise enhanced.

The participants included healthy people as well as individuals suffering from Alzheimer's, autism, schizophrenia and fetal alcohol syndrome.

"What scientists do is take things apart and study one little thing at a time ... This atlas allows us to put it all together again," said Toga, who calls the brain "the last great frontier of human biology."

The atlas, available on-line at http://www.loni.ucla.edu/ICBM , enables brain experts worldwide to access four-dimensional details -- time as well as the three dimensions of space -- of brain structure and function, descriptions of how the brain changes as we age and how and where neurological disease occurs.

The project is funded by a number of sources including the National Institutes of Health (news - web sites).


MORE CONFIDENCE IN DIAGNOSIS

"Eventually, it will be used to compare against disease populations. It will give clinicians more confidence in a diagnosis," Toga said.

The project is comprised of high-definition structural maps of individual brains based on age, race, gender, educational background, genetic composition and other distinguishing characteristics. Layered over the anatomical maps are animations of brain functions such as memory, emotion, language and speech. Users can look at individual brain pictures, composite pictures of subgroups by, for example, age or gender or as a composite of all 7,000 participants.

Toga has overseen brain scans of hundreds of people who tested within a typical range on measures such as blood pressure and pulse. Scans were taken while the subjects were at rest and while they performed a series of tasks, from focusing on a picture of a checkerboard to responding to sounds, to capture how the brain responds to stimuli.

"The brain handles the challenge of thinking of and initiating a word, and of understanding that word, differently. Execution of these tasks involves complex circuitry throughout the brain," said Mazziotta.

These differences between brains make it difficult to know what is normal and what is not. The atlas is also expected to be a guide for brain surgeons, who may not be able to actually view the critical areas in a patient's brain.

The atlas project is promising, but it is too early to say how relevant it will be as a medical tool, said Dr. Mony De Leon, director of the New York University Center for Brain Health who is not connected with the atlas project.

"It could be used as an indicator to tell you whether part of the brain is outside of normal limits, but someone still has to interpret the results," he said.

"If a pattern can be reliably determined, it will be an advantage in compiling evidence to demonstrate clinical relevance," De Leon said.

The project "will probably never end," said Toga. "The point is to continue to refine and continue to add data."

The consortium is in the process of expanding the data base to include younger and older age groups as well as brain scans from people with various neurological diseases.

http://www.loni.ucla.edu/

http://www.loni.ucla.edu/ICBM/