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[P]
Second in a series : How neurons transmit information

By Sgt York in Science
Tue Dec 07, 2004 at 07:11:03 PM EST
Tags: Science (all tags)
Science

So far, we have covered the propagation of an action potential, but not its source nor its effects. To address these, we will examine the example of the sympathetic ganglia. The sympathetic ganglia (or sympathetic chains, or paraveretebral ganglia) are conglomerations of lumps of neuron cell bodies, connected by conduits of axons, all of which run along each side of the spinal cord. These are responsible for coordinating, propagating, and assisting in the control of the sympathetic branch of the autonomic nervous system. Now, for this discussion, it's not so important what the sympathetic nervous system does. We're just interested in the structures. The autonomic system is different from some of the other nerves you are used to, in that normally they form at least one synapse outside the central nervous system before hitting whatever their target may be. A signal originating in the spinal cord will intersect a neuron in the ganglion, and the signal must jump from the spinal neuron to the neuron in the ganglion. In order to do this, it must cross the synapse.


A synapse is a tiny gap between two neurons, or a neuron and its target tissue. The action potential cannot cross this gap, so the electrical impulse is transformed into a chemical signal that carries the impulse along to the next cell to have some effect. The effects can be quite varied, from acting as a simple relay of the signal to altering the metabolic state of the downstream cell, or altering the regulation of its genes. The simplest of these is an excitatory postsynaptic potential, which we will examine here.

OK, back to the ganglion. In the simplest case, a neuron will extend its axon from the spinal cord and form a synapse with a cell body in the ganglion. Consider an action potential traveling down this axon. It will propagate along, the depolarization of the membrane causing a cascade of opening and closing voltage gated ion channels down the axon until it reaches the bulbous structure at the end, the terminal bouton (aka, terminal knob). Here, the makeup of the plasma membrane changes. Mixed among the voltage gated sodium channels are various other ion channels, such as a voltage gated calcium channel. As you would expect, this channel behaves in a manner similar to the voltage gated sodium channel. It opens when the membrane is depolarized and allows calcium to flow into the cell. The terminal bouton has another feature important for our discussion — It is full of vesicles. These are little membrane bound bags stored in the bouton. In each "bag" is a mixture of neurotransmitters, small molecules or peptides that will act on the postsynaptic cell in some way. In our preganglionic sympathetic neuron, these vesicles are filled predominantly with acetylcholine.

As the wave of depolarization washes over the terminal bouton, these channels open, and the concentration of calcium inside the bouton rises. This calcium influx starts a cascade. First, it binds to an small protein inside the cell, called calmodulin (CaM). When bound to calcium, CaM changes its shape, and can then bind to other proteins in the cell that act as enzymes, altering the structure and activating other proteins involved in the scaffolding support matrix of the cell. All these work together to start moving some of the vesicles towards the end of the bouton, the part facing the small gap, the synaptic cleft, between the bouton and the next cell. Once the membrane around the vesicle comes in contact with the plasma membrane, another cascade starts and the two membranes fuse, dumping the contents of the vesicle into the gap. Normally, only one vesicle will make it all the way to the membrane. The rest stop before they get there. Sometimes, if there is a lot of stimulation, two or three may fuse.

Once in the gap, the acetylcholine (ACh) is faced with a gauntlet to run. The cleft is full of an enzyme called acetylcholinesterase, bound to the membranes and floating in the cleft. This is an enzyme capable of breaking down acetylcholine into a pair of inactive products that are then reabsorbed by the neuron that just dumped it out (this is reuptake). The ACh that does make it across can then bind to a protein on the postsynaptic cell. In our scenario, this is a nicotinic cholinergic receptor (nACHhR), a new type of ion channel — a ligand gated ion channel. Instead of being opened by a change in voltage, these are opened by the presence of a small molecule that specifically binds to it, known as a ligand. In our scenario, ACh is the ligand. These proteins are among a group of proteins called receptors. Receptors are not restrcted to neurons, nor are they always ion channels, but they all cause changes in a cell in response to a ligand.

When ACh binds to this receptor, it opens and allows an influx of sodium, pushing the cell towards depolarization. If enough of these channels are stimulated at once, the membrane potential will cross the threshold and a new action potential will start. This is an example of the simplest case — an excitatory postsynaptic potential.

But, as is said frequently in biological sciences, it's never really that simple.

The changes in voltage instigated by the opening of one channel are transient, restricted in space, and small in magnitude. They will quickly dissipate, and the membrane will return to its resting potential. These also only affect a small area of the plasma membrane; the drop in polarization is over only a very small area. Therefore, these signals must be summated both spatially and temporally. There must be enough signals received in a small enough area, and over a short enough period of time to force the membrane potential across the threshold. And even that is simplifying matters a bit.

Each neuron has a large number of synapses, of wide variety. On average, each central nervous system neuron receives input from about 2000 synapses that are spread out over the cell body, dendrites, axon and bouton. Not all of these are excitatory, nor are they all postsynaptic. Some synapses express GABA or glycine receptors, which are ligand gated chloride channels on the cell. Chloride has a negative charge, and is concentrated outside the cell. Opening a chloride channel will hyperpolarize a cell due to the influx of negative charge, which will make the cell harder to depolarize for a short time. This is an inhibitory potential, and can be post or presynaptic (normally on or near the bouton).

Presynaptic signals can hyperpolarize the terminal bouton, effectively quenching the inbound action potential. Other presynaptic inhibitory potentials inhibit the calcium channels on the bouton, interrupting the signal before it is passed to CaM. Other neurotransmitters are modulatory, and affect the metabolism of the target cell. These modulatory neurotransmitters don't normally act through ion channels, and have longer lasting effects. These can alter gene regulation, cause a reduction or increase in the number of excitatory or inhibitory receptors, affect scaffolding proteins, affect the milieu of neurotransmitters in that cell's bouton, reduce the sensitivity of CaM to calcium (this is a very recent discovery), change the localization of the receptors, or a host of other effects. In our example, the target neuron in the ganglion will receive input from other spinal cord neurons and from neurons in other parts of the paraveretebral chain. This input will be summated, and the signal will be sent out, or it will not.

Our ganglionic neuron must summate all of these inputs, inhibitory, excitatory, and modulatory before transmitting a signal. In the end, this signal is binary. It is a decision whether the neuron will fire, or it will not. Whether and action potential will propagate down the axon, or not. In our example, the downstream effects are immediate. A blood vessel will constrict, or a bronchiole will dilate, or a sphincter in the GI tract will close. In the central nervous system, complexity becomes further complexity. Here, the individual signal summated from thousands will itself become one more signal among thousands to be summated at the next neuron.

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Second in a series : How neurons transmit information | 89 comments (67 topical, 22 editorial, 0 hidden)
As one entering the field (none / 1) (#2)
by Sen on Mon Dec 06, 2004 at 03:42:01 PM EST

I want to work with sensory devices as well as brain readers. There is also a "hail mary" chance that sentience is located at specific ganglia in the thalamus. Speaking of which, the one thing that really annoys me is how we must call brain ganglia "nuclei".

Well, actually (3.00 / 3) (#3)
by Sgt York on Mon Dec 06, 2004 at 03:55:53 PM EST

There is a difference between nuclei and ganglia. Ganglia are encapsulated clumps of neural tissue typically surrounded by predominantly non-neural tissue. Nuclei are concentrations of neuron cell bodies situated inside neural tissue. Nuclei only have to be histologically apparent, they have no capsule. You could pull out a ganglion easily, but not a nucleus.

Most of the distinction is anatomical (the capsule), but there is an important functional distinction as well: the absence of a capsule makes a nucleus more plastic.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Gotcha (none / 0) (#5)
by Sen on Mon Dec 06, 2004 at 05:30:24 PM EST

Lemme see if I remember, you're the biochemistry guy? So I see the reason. I'll just add it to my "words that need to be added list". Just hearing it in class irked me, as I kept thinking of soma nuclei. Wouldn't "neuron cluster" be ok?

[ Parent ]
Neuron cluster (none / 0) (#6)
by Sgt York on Mon Dec 06, 2004 at 05:46:37 PM EST

Not specific enough, really. It's correct, but not precise.

Some of the terms can get annoying, I know. But there is a reason for all the jargon (well, there's a reason for most of the jargon): It makes it easier to effectively & succinctly communicate what you are thinking. Saying "neuron cluster" may refer to a neuroma, a ganglion, a nucleus, a plexus, or any other lump of neurons. Also, since you aren't specifying somas, you could be talking about funiculi or nerve trunks. Saying "nucleus" communicates exactly that: A distinct but not well defined cluster of somas in the CNS.

And yeah, I'm the biochemistry guy.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Brain nucleus then (none / 0) (#8)
by Sen on Mon Dec 06, 2004 at 05:54:16 PM EST

As opposed to cell nucleus. That way it's the correct term and is more clear. I'm getting to know the terms and I wish there were more, not less! If neuroscience is the bridge to transhumanism, language issues pale.

[ Parent ]
Ah (none / 0) (#9)
by Sgt York on Mon Dec 06, 2004 at 06:14:35 PM EST

You're talking about nucleus in cell bio as opposed to neuro. Yeah, that gets a good number of people. Normally, people will refer to nuclei in the CNS as "basal nuclei", "nuclei of the brain stem", "nuclei in the dorsal horn", etc. They'll add a little specificity as to the location. Also, a cell nucleus is often expressed just that way "cell nucleus" or "cellular nucleus".

Also, you rarely talk about cell nuclei and CNS nuclei at the same time. So that helps in the real world, too.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Function of different neurotransmitters? (2.50 / 2) (#19)
by MichaelCrawford on Tue Dec 07, 2004 at 04:29:07 AM EST

There are several different neurotransmitters, and they have different roles in mental illness. Insufficient serotonin or norepinephrine will make you depressed, excesses will make you manic. Excess dopamine activity causes paranoia and hallucinations, symptoms of schizophrenia. Lack of dopamine causes sleeping sickness, and can be (temporarily) treated with the dopamine precursor L-dopa, as documented in Oliver Sacks' Awakenings.

Now, my question to you is, do different neurons in the brain use different neurotransmitters? Do some use dopamine, and others serotonin? Or do all the cells use all three, but for different effects? Why doesn't excess dopamine make one manic, as excess serotonin would?

Thanks in advance.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


Both are correct (3.00 / 2) (#20)
by Sgt York on Tue Dec 07, 2004 at 04:56:36 AM EST

Different neurons use different neurotransmitters, and some neurons use the same neurotransmitter to different effects.

Here, I talked about how ACh can stimulate a neuron to depolarize via the nicotinic ACh receptor (nAChR). There are also muscurinic ACh receptors (mAChR), which mediate (among other things) slowing of the heart, gut motility, and even play a role in establishment and maintenance of memory. Even nAChR's can have different effects, depending on the cell they are on. Here, a nAChR pushed a neuron towards depolarizing, which would propagate the signal. The same receptor is expressed on muscle, and has the same immediate effect, to depolarize the cell. But instead of propagating a signal in respnose to the depolarization, the muscle will contract.

It has a lot to do with the receptors on the postsynaptic cell and the cell type (other effects have to do with cell state, which gets into plasticity, which is FAR too complicated to discuss adequately here). Administering dopamine to a cell expressing only serotonin receptors will have no effect. Administering dopamine to a cell expressing the D1 dopamine receptor will have one effect, but if that same cell were changed to express D2 instead, the effect would be opposite, even with the same drug!

To make things even more complicated, a neuron will normally express one receptor type at one synapse, but express other receptors at other synapses. And there are MANY different neurotransmitters. You mentioned epinephrine, serotonin, and dopamine. But there is also glycine, GABA, adenosine, the opioids, substance P, histamine, glutamate, neuropeptide Y, and scores of others. Each has its own receptor (more or less), and eachhas its own effect, which will vary from cell to cell.

(I hope all that made sense....it's been a long day)

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

I'm thinking of writing a book... (none / 0) (#21)
by MichaelCrawford on Tue Dec 07, 2004 at 05:41:17 AM EST

... to expand on what I wrote in Living with Schizoaffective Disorder. One thing I'd like to do is to discuss the physiology of mental illness, and its treatment, in a more detailed way than is commonly done in books for non-specialists.

There are a number of books with personal accounts of mental illness, but few of them go into any technical detail. There are many books for psychiatrists and psychologists, that are quite technical, but not accessible to someone who hasn't had years of university study in medicine or psychology.

The one exception I know of is The Noonday Demon: an Atlas of Depression by Andrew Solomon. I've only skimmed through it a little so far, but my understanding is that he discusses not only his own experience with depression, but how depression works in the brain, and how its treatment works. I'd like my book to be like that.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


[ Parent ]

I don't know you (none / 0) (#89)
by Reductio on Tue Dec 21, 2004 at 12:09:11 PM EST

But I believe that you are doing drug companies a service and the public a disservice by supporting the current practice of prescribing drugs to treat mental illness. Please stop.

[ Parent ]
hmmmm (none / 0) (#22)
by forgotten on Tue Dec 07, 2004 at 06:15:10 AM EST

from my ... ah ... research, excess dopamine certainly will make you manic.

--

[ Parent ]

Me too. (none / 0) (#23)
by Empedocles on Tue Dec 07, 2004 at 06:35:23 AM EST

It was for scientific research purposes only, Your Honor.

---
And I think it's gonna be a long long time
'Till touch down brings me 'round again to find
I'm not the man they think I am at home

[ Parent ]
I don't need drugs to get high (none / 0) (#24)
by MichaelCrawford on Tue Dec 07, 2004 at 06:37:51 AM EST

I need them not to.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


[ Parent ]

I tried that one, too. (none / 0) (#26)
by Empedocles on Tue Dec 07, 2004 at 07:33:02 AM EST

It didn't work very well. The guy threw the book at me.

---
And I think it's gonna be a long long time
'Till touch down brings me 'round again to find
I'm not the man they think I am at home

[ Parent ]
Serotonin (none / 0) (#25)
by pickpocket on Tue Dec 07, 2004 at 06:38:32 AM EST

You're right that temporary high serotonin levels can trigger mania, particularly in people predisposed towards it. However, there's only one disorder that's associated with chronic hyperserotonemia: autism.

[ Parent ]
plasticity (2.25 / 4) (#27)
by MichaelCrawford on Tue Dec 07, 2004 at 08:09:34 AM EST

I seem to recall that my psychiatrist told me that there was a phenomenon I'm pretty sure he called "plasticity", which meant that the number of neurotransmitter receptors varies over time.

He said that was likely the reason that I now have to take five milligrams of risperdal each day to keep my head screwed on straight, where it used to work just fine to take only two.

Without risperdal, the CIA would be tapping my phone and I'd be seeing police cars everywhere. With it, I can be Insightful, Informative, occassionally Funny, and even get Encouraged.

I believe the function of antipsychotics like risperdal is to block dopamine receptors. So my shrink says I just have more receptors than I used to.

Could you enlighten me more about this.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


Plasticity (3.00 / 4) (#33)
by Sgt York on Tue Dec 07, 2004 at 11:13:09 AM EST

Plasticity encompasses many things, but in a nutshell, it is the ability of cells to change in response to signals and other aspects of their environment. The drug you are taking is blocking a specific dopamine receptor (and probably a specific serotonin receptor as well).

To put it simply, when a receptor is stimulated a lot, less of it is made and evetually there is less of it around. The reverse is true, as well. If a receptor is not stimulated, more of it is made, and pretty soon you have a lot of it around. Since yor drug antagonizes (opposes the ability of ligand to act on) the receptor, there is less stimulation, so your cells make more receptor. You now need more drug to have the same effect, simply because there are more receptors around; there is more work to be done than before. Some receptors reach a saturation point; they can only go up so high before they cannot be up regulated any more. I don't know if these specific receptors exhibit this feature or not.

I would wager that most people on K5 have encountered this phenomenon. Caffeine inhibits (antagonizes) adenosine receptors, one of which (A1) is one of those inhibitory modulatory receptors I talked about in the article. Inhibition of A1 causes a generalized increase in central nervous system activity, which is a mechanistic way of saying "it wakes you up". It also causes an increase (aka "up regulation") of the A1 receptor. You therefore build a resistance to caffeine (just like you did with the risperdal), and need to take more to get the same effect.

Teh suck comes in when you skip the coffee one day. You now have assloads of A1 on your neurons. As a result, when adenosine is released, there is a much greater response in the downstream cell, severely depressing its ability to resond. This makes the coffee drinker even more lethargic than he would have been otherwise. Furthermore, adenosine plays a role in vasodilation (increasing bloodflow) via another receptor. This receptor is also up regulated, and the abnormally high level of signal causes greater than usual bloodflow into the space inside the skull. This swells certain structures inside the skull, and the pressure is felt as a headache.

Sorry about the technical terms. Some definitions:

Teh suck : clinical level of pathology

Assload : Greater than 3 fold induction as measured in agonist (NECA) binding per unit membrane surface area

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Can you suggest some light reading? (none / 0) (#35)
by MichaelCrawford on Tue Dec 07, 2004 at 11:21:13 AM EST

I'd like to better understand the mechanisms behind mental illness, to the extent they're understood at all, as well as its treatment. Can you suggest some books or magazine articles to read?

I think one of my strengths as a writer is that I'm good at explaining complex topics in a way that most anyone can understand. If I were able to understand brain chemistry in more detail, possibly if I wrote that book I mentioned earlier, I could do a good job of helping lots of people understand what's really going on when someone is schizophrenic or bipolar.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


[ Parent ]

Light reading.... (none / 0) (#36)
by Sgt York on Tue Dec 07, 2004 at 11:45:13 AM EST

Hmmm....Well, most of what I read is primary journals, written for researchers. The "lightest" would be the Nature Reviews set of journals. Start with the neuroscience one, and scan for interesting looking articles. Most are written for a generalized audience, so terms are explained and things are kept fairly simple and narrative. But it still may be challenging for the uninitiated.

My personal favorite textbook on receptors is Signal transduction, by Gomperts & Tatum. But still, it may be a bit technical. Other books that would be helpful are Molecular Cell by Lodish. Medical Physiology by Guyton & Hall is pretty good, but has some errors when it comes to gene regulation. Refer to Lodish for gene regulation stuff.

I'm sorry I'm not of more help, I normally don't pay a lot of attention to popular press for science books. I just read journals.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Journals are fine (none / 0) (#37)
by MichaelCrawford on Tue Dec 07, 2004 at 12:05:01 PM EST

As the joke says, "I may be crazy, but I'm not stupid". I had a year of chemistry and a quarter of biology at Caltech, and Bonita got a degree in biology before she decided to become an artist, so I expect she could help me.

Thank you very much for your excellent article, and your helpful answers to my questions.

It's going to be a long time, I expect, before I'm able to write my book. I've only just begun to think about what I'll say in my proposal.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


[ Parent ]

Glad it was useful (none / 0) (#38)
by Sgt York on Tue Dec 07, 2004 at 12:37:51 PM EST

Try out those reviews. Also, if you're not already familiar, check out pubmed. Be sure to go to "limits" and select "reviews" under "article type". Reviews are a bit less dry, and give an overview of processes rather than heaps of lovely, intimate data.

I think a book like you are proposing is an outstanding idea. Technical information presented alongside personal knowledge could make for a very interesting read. I just came accross your articles from last year (wasn't a member at the time) and I've started reading them. Very good stuff.

Good luck on your research for your book, and if you have any other questions, I'll do my best to answer.


There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

Thats a big ask (none / 0) (#50)
by GenerationY on Wed Dec 08, 2004 at 06:44:18 AM EST

Its a little like saying, where can I find out about the mechanisms that govern the nature of matter and energy...

I guess you are looking for something on the biological bases of behaviour.

The first thing is probably to just go and grab a undergrad textbook on Abnormal Psychology. They are all pretty much the same to be honest and your local library will be heaving with them.

I'd follow the paper trail from there really. Its probably the most efficient route rather than buying a lot of texts or whatever. Much of this material is recent enough that the definitive books haven't necessarily been written, unlike some other areas of research and learning.

A good solid textbook on the wetware is Kandel's Principles of Neural Science. Nice to have a textbook written by a Nobel laureate I think (not really my thing, but I'm a Kandel fanboy for some reason). I wouldn't buy it, but locate it in the library and photocopy chapters as you need them.

But I think you have to realise this is a very complex problem where its pretty hard to nail anything down definitively. There is science, rationality and even underlying mathematics here, but I know a lot of people with a background in Physics and Engineering get very frustrated at times with the whole area for not being more exact. The biologists and neuroscientists can of course create ver accurate data these days, but behaviour remains to some extent an enigma. And if you want to understand dysfunction you need to marry the two.

One of the difficult issues with mental health is defining dyfunction when we find it difficult to define function. Some have argued that we worry too much about the negatives and the dysfunctions at the expense of understanding the positives; hence the Positive Psychology movement, which you might also be interested in looking into.

[ Parent ]

Book recommendation (none / 0) (#74)
by dn on Sat Dec 11, 2004 at 03:35:15 AM EST

The Second Brain, a fairly accessible book about the enteric nervous system, which controls the gut. It takes a surprising amount of smarts to run the digestive process, keep the bacteria from taking over, and keep the loss of water and salts to acceptable levels.

    I ♥
TOXIC
WASTE

[ Parent ]

Another Question (none / 0) (#61)
by brain in a jar on Thu Dec 09, 2004 at 07:28:33 AM EST

Does this plasticity and the example you give with caffiene imply a more general rule?

I.e. If you consume some kind of pyschotropic drug regularly, when you stop consuming it you will experience the its effects in reverse to some extent.

Could this explain why alcoholics often seem nervous when they are sober?


Life is too important, to be taken entirely seriously.
[ Parent ]

Fairly general (none / 1) (#62)
by Sgt York on Thu Dec 09, 2004 at 11:01:21 AM EST

This type of regulation is common enough to be considered a rule. It's common enough so that it's normally mentioned when a receptor doesn't do it.

It happens frequently, but I don't think it happens always. Also, "opposite" will be the physiological or neurological opposite, not necessarily what we would consider opposite logically.

It does help explain the behavior of heroin and cocaine addicts upon withdrawl, but I'm not sure if enough is known about the action of ethanol to say for certain.

Ethanol probably does not work through a single receptor or receptor group like cocain does.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

The DTs (none / 0) (#63)
by MichaelCrawford on Thu Dec 09, 2004 at 01:28:32 PM EST

I'm not really sure, but someone told me the reason alcoholics get the DTs when they stopped drinking is that the alcohol damages the mylin sheath around their nerve cells, I think by dissolving some of it away.


--

Live your fucking life. Sue someone on the Internet. Write a fucking music player. Like the great man Michael David Crawford has shown us all: Hard work, a strong will to stalk, and a few fries short of a happy meal goes a long way. -- bride of spidy


[ Parent ]

DTs (none / 0) (#75)
by dn on Sat Dec 11, 2004 at 03:53:22 AM EST

Alcohol enhances the effects of GABA, an inhibitory neurotransmitter. With chronic use the GABA system gets downregulated, and other excitory systems get upregulated. (The brain's feedback loops are very conservative about maintaining their chosen equilibrium.) If the alcohol suddenly disappears, there is not nearly enough GABA to inhibit neurons, and there is way to much of the other things that are stimulating neurons. The result is a brain that is stuck in overdrive, possibly to the point of having seizures and even neuron death. The classic treatement is a benzodiazepine like Valium, which is a GABA agonist that can take the place of alcohol but without all the other toxic effects.

The scary thing is I barely had to look that up. Why do I know such useless crap? I'm not a doctor or an alcoholic...

    I ♥
TOXIC
WASTE

[ Parent ]

+1FP! So very hungry for good brains storys!! (1.33 / 6) (#39)
by Zombie Pol Pot on Tue Dec 07, 2004 at 03:49:42 PM EST

Zombie Pol Pot so happy for seeing story on brains working, not sending you for Killing Fields! Only problem needing more recipes for zombies! Letting you off and give +1FP for story but you must giving zombie katjap or fish sauces for eating fresh synaptic brains from lame posters on story! So very hungry!

There are books for beginners which... (1.33 / 3) (#40)
by Uber Banker on Tue Dec 07, 2004 at 05:03:07 PM EST

...describe this better.

yes, but (1.00 / 2) (#41)
by gdanjo on Tue Dec 07, 2004 at 07:11:09 PM EST

Where does the soul fit in all this?

Dan ...
"Death - oh! fair and `guiling copesmate Death!
Be not a malais'd beggar; claim this bloody jester!"
-ToT

that's obvious (none / 1) (#49)
by Roman on Wed Dec 08, 2004 at 12:53:37 AM EST

there is no soul.

However in russian there is a saying, after you visit a washroom - "the weight off the soul", which shows that the sould can be found underneath the bladder.

[ Parent ]

if there is no soul (none / 0) (#56)
by gdanjo on Wed Dec 08, 2004 at 07:24:49 PM EST

then there is no Roman, either.

Dan ...
"Death - oh! fair and `guiling copesmate Death!
Be not a malais'd beggar; claim this bloody jester!"
-ToT
[ Parent ]

Faulty logic (none / 0) (#57)
by Roman on Wed Dec 08, 2004 at 08:17:05 PM EST

Roman is a set of constantly changing data and functions. Soul is just a metaphor for this mix.

[ Parent ]
au contraire (none / 0) (#58)
by gdanjo on Wed Dec 08, 2004 at 09:20:34 PM EST

Roman is a set of constantly changing data and functions. Soul is just a metaphor for this mix.
And "earth" is just a metaphor for "lots of dirt, and stuff poking out of it."

My point being that deconstruction may be useful in understanding the bits of the whole, but in this deconstruction you lose the essence of the whole. Yes, you're just "changing data and functions", but you're more than just Microsoft Word with Patches and Extendible Modules.

Dan ...
"Death - oh! fair and `guiling copesmate Death!
Be not a malais'd beggar; claim this bloody jester!"
-ToT
[ Parent ]

Yes, we have a soul (none / 0) (#60)
by DeepOmega on Thu Dec 09, 2004 at 01:21:14 AM EST

but it's made of lots of tiny robots.

Peace and much love...
[ Parent ]

Consult your pineal gland. (nt) (none / 0) (#64)
by ksandstr on Thu Dec 09, 2004 at 07:07:36 PM EST



[ Parent ]
Pun-da-mental (2.33 / 9) (#43)
by asliarun on Tue Dec 07, 2004 at 07:52:53 PM EST

Did you hear about the lesser known but highly controversial Jane Goodall story? It seems that on her last visit to Africa in 1987, she was accompanied by one of her new students, Ronald Foom. Now, Ronald, not unlike his famous teacher, had an intense and all-consuming desire to learn more about the African Chimps. Being only a struggling student, and one out of the fifty-odd who accompanied Ms Goodall on the year long field trip, Ronald had a burning desire to use this opportunity to outshine the others and be counted with the best.

He slaved during the night poring over the semianal works in animal behaviour and psychology. During the day, he would use his new-found knowledge to perform social experiments on the chimps. Increasingly being distracted by the fumbling efforts of others, he started venturing deeper and deeper into the forest, in search of the perfect chimp family. At last, he struck gold. He found a chimp family of ten, completely secluded and untouched by mankind, in a corner of the jungle where even Jane Goodall would not dare to venture.

Having found his catch, Ronald set about assimilating himself into the chimps' social network, and by slowly communicating with them by using sign language. To his astonishment, he found that he was making terrific progress. Within six months, he had completely taught sign language to the ENTIRE group. This was unheard of! The only other success in teaching a chimpanzee sign language was attributed to the grand mistress herself, and she too had only been able to teach sign language to one single chimpanzee after labouring for ten years.

Not able to contain his excitement, Ronald ran back to the camp to tell the others of the good news. The chimps, who had become very attached to this strange but lovable hairless creature, followed him to the camp as well. When Ronald demostrated his accomplishment to the rest of the team, they were too stunned to speak! Then, as if on cue, they broke out into an uproar, and started clamouring Jane Goodall to make this news public.

However, to the dismay of everyone, Jane declined to endorse Ronald and his accomplishment. When challenged, she simply remarked:-
"Hmph, what's so terribly exciting about this? Everybody knows that a new Ron has multiple Sign Apes."

+1FP (none / 0) (#76)
by dn on Sat Dec 11, 2004 at 03:54:38 AM EST


    I ♥
TOXIC
WASTE

[ Parent ]

Please, please ...! (none / 0) (#86)
by k24anson on Tue Dec 14, 2004 at 11:30:36 AM EST

No applause people, please! Just throw money.
KLH
NYC

Stay focused. Go slow. Keep it simple.
[ Parent ]

What's with the wierd spacing? (none / 0) (#44)
by Sen on Tue Dec 07, 2004 at 09:35:54 PM EST

Too late now, but realizing some commas have two spaces after them for some reason. It's not even right-justified either.

Editor (none / 0) (#47)
by Sgt York on Tue Dec 07, 2004 at 09:59:30 PM EST

Where were ya this morning, huh? You're right...that is weird. I think it's an artifact from cutting and pasting from OpenOffice.

And I didn't even know you could right justify. How do you do that?

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

HTML magic? (none / 0) (#48)
by Sen on Tue Dec 07, 2004 at 11:11:16 PM EST

It can even be done with a monospace font, but will look really ugly then.

[ Parent ]
Saw it... (none / 0) (#51)
by pwhysall on Wed Dec 08, 2004 at 11:19:37 AM EST

...thought “I&rsqou;ll have a look at that this afternoon”. I come back, and it’s gone to the FP.

I’ll sort it out.
--
Peter
K5 Editors
I'm going to wager that the story keeps getting dumped because it is a steaming pile of badly formatted fool-meme.
CheeseBurgerBrown
[ Parent ]

Arse. (none / 0) (#52)
by pwhysall on Wed Dec 08, 2004 at 11:20:08 AM EST

I previewed, too. Gah.
--
Peter
K5 Editors
I'm going to wager that the story keeps getting dumped because it is a steaming pile of badly formatted fool-meme.
CheeseBurgerBrown
[ Parent ]
Lots of reverse transmission too (none / 1) (#45)
by Sen on Tue Dec 07, 2004 at 09:51:07 PM EST

Nitrous oxide qualifies as a retrograde transmission to the presynaptic cell. There was also a Scientific American about additional chemicals that made their way back to the presynaptic axon.

An axon needs to know it has a valid and active synaptic connection or it may die by apoptosis (we make many more neurons than we need to). Some signal could be coming the other way for this.

NO (none / 0) (#46)
by Sgt York on Tue Dec 07, 2004 at 09:57:49 PM EST

NO is certainly a unique neurotransmitter, and not just because it acn act retrograde. It can also act on nearby neural and non-neural cells that don't even synapse. NO is certainly one of the cooler signaling molecules out there.

I was unaware of the apoptotic pathway before. The only role I had heard for NO in apoptosis was mediating via DNA damage.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

<pedant> that would be nitric oxide (n/t) (none / 0) (#84)
by cyrus on Mon Dec 13, 2004 at 12:53:26 PM EST


~c
[ Parent ]
Let's change it (none / 0) (#53)
by Sen on Wed Dec 08, 2004 at 11:42:07 AM EST

I had a bad reaction to a psychiatric drug and my whole head twisted to the right. An anti-cholinergic calmed it down. It was very wierd and not fun. Apparently a few cranial nerves went a little crazy.

I can't imagine wanting to copy nature when we create our transhuman selves. Chemical synapses are slow and prone to problems.

I had that too (none / 0) (#65)
by bg on Thu Dec 09, 2004 at 10:26:01 PM EST

Nasty shit. Don't remember the name of the drug or what it was for. Perhaps an antipsychotic?

- In heaven, all the interesting people are missing.
[ Parent ]
Risperdal (none / 0) (#69)
by Sen on Fri Dec 10, 2004 at 02:15:02 PM EST

Psychoactive, just forgot what it does.

[ Parent ]
Hmm (none / 0) (#78)
by bg on Sun Dec 12, 2004 at 01:53:25 AM EST

I never had that problem with risperdal.

- In heaven, all the interesting people are missing.
[ Parent ]
reaction too (none / 0) (#85)
by k24anson on Tue Dec 14, 2004 at 11:25:40 AM EST

Prolixin paralyzed me for like twenty, thirty hours; they thought it might eventually stop the autonomic heart/breathing reflexes. I was told they had to inject me with something, only to be able to say later in a court of law that they did do something to treat me. Legal concerns and not my immediate psychiatric condition ( I wasn't socializing with the other patients on the ward) decided whether I was to get an intramuscular glute shot of Prolixin, so I was later told.

I had counsel inform me I had cause to sue the people at Marcy (New York) for what happened. I'm not the litiguous type.

So it goes.
KLH
NYC

Stay focused. Go slow. Keep it simple.
[ Parent ]

Tardive Dyskinesia (none / 0) (#88)
by Reductio on Tue Dec 21, 2004 at 10:55:30 AM EST

And it hurts like a mother. Got it from Haldol. The doc fixed it with Benidril, but that had its own side nasty side effects (Like the people on the TV talking to/about me) Respirdol worked will with cogentin to stop some of the side effects. Best solution - get yourself off of meds and have your brain regulate its chemistry like it's supposed to.

[ Parent ]
synaptic depolarizations (none / 0) (#54)
by Terren on Wed Dec 08, 2004 at 05:21:49 PM EST

It's easy to assume that action potentials only travel from the dendrites to the cell body, and on through the axon. But is that assumption wrong?

If a depolarization originates at a synapse, doesn't the action potential actually travel in all directions away from the synapse (assuming all surrounding ion channels are in the 'rest' state)?

If so, that significantly complicates the picture of how/whether action potentials make it to the cell body.

Reversing the AP (none / 0) (#55)
by Sgt York on Wed Dec 08, 2004 at 05:56:38 PM EST

If an axon were depolarized in the middle, the AP would propagate in both directions. The problem is that synapses on the axon are rare, and those that do occur are normally inhibitory (hyperpolarizing). Same goes for the ones on the bouton, though those are much more common.

Two APs that collide really wouldn't interefere, anyway. They are both depolarizations, so neither would cancel the other out. Also, since an AP is "all-or-nothing", you don't get any positive interference, either.

The only way you'd get any meaningful interaction would be if an AP hit a hyperpolarized region. This would make it so that when the AP enters the hyperpolarized region, it is not enough to bring the potential to threshold. And this is an inhibitory potential (GABA, etc).

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

if two APS collide... (none / 1) (#66)
by Terren on Thu Dec 09, 2004 at 10:46:52 PM EST

My understanding is that if two APs going in opposite directions met, they'd both abruptly stop. Directly behind each AP, ion gates shut and stay shut to turn off the flow of charge, and that would kill both waves as they "ran into" each others' wake.

[ Parent ]
You're right (none / 0) (#72)
by Sgt York on Fri Dec 10, 2004 at 04:16:44 PM EST

I just pulled that out off the cuff, thinking theoretically and spouted that off. If two AP's collide, both will halt immediately due to the refractory phase.

I had actually forgotten about it until I saw your reply. Thanks for the correction.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

explanation (none / 1) (#59)
by cyrus on Wed Dec 08, 2004 at 09:30:40 PM EST

As i understand it, action potentials tend not to be generated in the dendrite, but rather that the depolarisation caused by the ligand gated channels is passively conducted to the start of the axon (called the axon hillock) which has particularly a low threshold for AP generation (due to high density of ion channels).

Now once the AP has been initiated there, it is free to propagate down the axon, and also I believe backwards through the cell body and dendrites to facilitate in potentiation.
~c
[ Parent ]

question (none / 0) (#67)
by Terren on Thu Dec 09, 2004 at 10:50:03 PM EST

Are there any non-synaptic ion channels in the dendrites? If so, than action potentials must be generated in dendrites. Indeed, anywhere voltage-sensitive ion channels exist, an action potential can be generated. So if any exist in the dendrites, synaptic events would trigger APs.

My question is, if this happens, doesn't that affect a hypothetical AP that was generated further down the dendrite?

[ Parent ]

Yes there are (none / 0) (#68)
by cyrus on Fri Dec 10, 2004 at 11:54:54 AM EST

There are non-synaptic ion channels (i.e. voltage gated ion channels) in the dendrites. However, their type and density must be considered before concluding that they are capable of AP generation and propagation in response to initial synaptic depolarisations. The traditional model I think assumes that they don't exist in a high enough density to be activated by typical synaptic depolarisations, i.e. the threshold potential for AP generation is high.

However there is growing evidence that dendritic voltage gated ion channels profoundly regulate axonal firing beyond the back-propagation i've already mentioned, but this goes beyond my current understanding as a second year medical student :-)
~c
[ Parent ]

problems with the traditional model (none / 0) (#70)
by Terren on Fri Dec 10, 2004 at 03:16:34 PM EST

First off let me thank you for responding to my questions. So you're saying that when the axon fires, according to the traditional model, it's because charge from one or more (excitory) synaptic events diffuses to the cell body, where it triggers a depolarization? In other words, the dendritic membrane doesn't, as a rule, depolarize? I'm skeptical of that for a few reasons. The first is, charge from a synapse far enough away from the cell body might all leak out before it got there. The second reason is the very presence of voltage-gated ion channels in the dendritic membrane. What would their purpose be, other than to propogate action potentials? Under what conditions do those ion channels open? If they ever open, you can see how that complicates the picture, because then you can no longer model the dendrites as a linear sum of synaptic charge. Finally, if dendritic charge did trigger voltage-gated ion channels, such nonlinear behavior would mean that the firing of a neuron is much more sensitive to timing of synaptic events. A nonlinear, timing-sensitive model of dendritic charge propogation has an advantage over the traditional model, given that neural firing varies in frequency, not amplitude.

[ Parent ]
Chiming in (none / 0) (#71)
by Sgt York on Fri Dec 10, 2004 at 04:12:05 PM EST

I think that the theory behind the nonsynaptic voltage gates is that they can help amplify regions of depolarization. They do not normally carry action potentials (their density is too low to do so), but they can amplify the depolarization resulting from the opening of any ligand gated channels in the area. This is another mechanism of plasticity.

The dendritic membrane does depolarize; it's just that there is not adequate machinery (i.e., insufficient density of voltage gates) to propagate an AP.

What this does is to set up a receptor potential; the membrane will have a gradually expanding region of depolarization in response to repeated EPSP's. The voltage gates on the soma can help expand and maintain this region somewhat. Once a region with sufficient magnitude of depolarization reaches the hillock, where voltage gates reach critical density, an AP is generated. (Altering the size of the area with that critical density is another mechanism of plasticity)

This is part of what allows gradation of response. A neuron will continue to fire (a series of AP's) as long as the receptor potential is above threshold in the hillock. If you consider that encroaching regions of varying polarization state are always creeping up on the hillock in response to synaptic changes, you can see you the cell could rapidly cycle between firing and nonfiring states. This will affect the frequency of AP outflow on the axon by reducing it from maximal (the rate of fire when the hillock remains depolarized) by diluting it with varying ammounts of time that the hillock is below threshold. The resulting summated rate of fire will affect the next nerve down the pathway. Increased rate of fire from the presynaptic nerve will allow its synaptic region of depolarization to spread further, essentially increasing the "influence" that neuron has on the postsynaptic neuron.

Sorry if this isn't making a lot of sense, this stuff is really hard to communicate verbally. I need a whiteboard, about 5 different colored markers, and a running potential calculation. I had wanted to get into all of this, because to me, it's the cool part. But I really can't think of a good way to explain it in this medium, I really just lack the skills.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

amplifying the signal is an AP (none / 0) (#77)
by Terren on Sat Dec 11, 2004 at 09:54:16 PM EST

If a voltage-gated ion channel opens to 'amplify the signal', I don't see how that's any different from what an action potential is. Whether you call it an action potential or not, what's happening is that a wave of positive charge propogates in a particular direction from the dendritic synapses and ultimately to the end of an axon. Action potentials only work because voltage-gated ion channels ahead of the 'wave' open in response to the membrane voltage going over the threshold. Whether that's happening at the nodes of Ranier or at 'amplifying' ion channels in the dendrites, the mechanism is the same ... isn't it?

Am I missing something?

P.S. Even though this medium isn't perfect for this kind of discussion, I understand everything you're saying, I think. Anyway, I appreciate the effort and answers to questions I've had for a while.

[ Parent ]

AP's are chain reactions (none / 0) (#79)
by Sgt York on Sun Dec 12, 2004 at 01:38:00 PM EST

The key is that an AP is self propagating; it is a chain reaction. That is, there are enough voltage gated ion channels (I'm sick of writing that out...cell 'em VGIC's) in region of membrane to cause a chain reaction.

Take three scenarios. In the first, there is a sparse population of VGIC's among ligand GIC's. If a LGIC is opened and the local membrane is depolarized, the closest VGIC may experinc enough of a change to open as well, amplifying the change. The VGIC closest to that VGIC, however, may be too far away for the voltage change to open it. The voltage change has dispersed along the membrane, and it is too weak to cause channel opening by the time it reaches that second VGIC. There is no chain reaction, and therefore no AP.

In the second scenario, the population of VGIC's is very dense. Here if one opens, its neighbors are close enough that the change doesn't peter out, and they open as well. The same thing happens at the next and the next, and the wave of depolarization does not diminish with distance.

In the last, all you have is the LGIC. Upon activation, this will cause a depolarization in the vicinity of the LGIC, but it will not be amplified as in scenario 1. The depolarization wave is not as great or as large; it dissapates very rapidly.

I'm glad everything so far has made sense, I hope that does, too.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

membrane leakage (none / 0) (#82)
by Terren on Sun Dec 12, 2004 at 10:06:47 PM EST

OK, I'm with you. But then my question is, if a synapse opens, and there isn't a high enough density of VGICs to propogate the signal, then how do any action potentials result at all? I've assumed that the reason VGICs were necessary was because charge leaks out of the membrane, and unless the synapse was very close to the soma, it would all leak about before it got there.

[ Parent ]
Summation (none / 0) (#83)
by Sgt York on Sun Dec 12, 2004 at 10:26:58 PM EST

This is where the concept of summation comes in. A lot of people get confused at this point because they are so used to the example of the neuromucular junction, which has a high density of VGIC's and acts like you are describing.

However, in a neuron, there are multiple synapses, and there can be a very high frequency of inbound APs at any given synapse. These are all summated. One synaptic firing is rarely (if ever) enough to fire a neuron. There must be several firings in a short timespan. These are summated, causing an ever growing depolarized region on the cell. Once this depolarized region reaches the hillock (where you have critical density of VGIC's), an action potential is initiated.

Controlling the ammount and concentration of VGIC's at and around specific synapses, and the size of the critical density region at the hillock are important aspects of plasticity.

There is a reason for everything. Sometimes, that reason just sucks.
[ Parent ]

thanks! (none / 0) (#87)
by Terren on Tue Dec 14, 2004 at 02:13:04 PM EST

Thanks for taking the time and energy, and I look forward to the third installment.

[ Parent ]
Second in a series : How neurons transmit information | 89 comments (67 topical, 22 editorial, 0 hidden)
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