[Neuroscience] Re: A hypothesis (Re: Can a single neuron release multiple neurotransmitters?)

Zachary Tong via neur-sci%40net.bio.net (by polyfractal At gmail.com)
Wed Jan 3 10:15:02 EST 2007

Thanks to both of you for the replies.  I wasn't aware previously about 
"fast" and "slow" transmitters.  I've got so much more research to do!  

A few more questions, if you guys don't mind.  While neurons may only be 
able to release a few types of transmitters, is it safe to assume that 
the post-synaptic end has many different types of receptors?  I've read 
that neurons can build more receptors.  If a post-synaptic neuron 
continually receives a large amount of one neurotransmitter, does it 
start to create new receptors for that particular transmitter, thus 
"strengthening" that connection the two neurons share?  It would make 
sense that if the pre-synaptic synapse continually releases one type of 
transmitter, the post-synaptic end would want to become more sensitive to 
that type.

Some more misc. questions.  Its obvious that parts of the brain favor one 
type of transmitter over another.  Its also true that the transmitter 
itself doesn't affect the neuron, rather the neuron "decides" (for a lack 
of a better term) how each transmitter will affect it.  Does this mean 
that the brain happened to evolve with one area using dopamine while 
another uses seretonin, but with no real practical difference?  Ie. could 
the brain have evolved another way (say, switching the two) and still 
function the same?  Is there any fundamental reason why one 
neurotransmitter would be used in place of another, or was it just the 
result of evolution in those particular parts of the brain?

Furthermore, the following quote explains that some receptors are 
inhibitory on a certain neuron, while the same receptor on another neuron 
is excitatory:

"One way of classifying synapses is whether the action of the 
neurotransmitter tends to promote or inhibit the generation of an action 
potential in the postsynaptic cell. Binding of a neurotransmitter to an 
excitatory receptor opens a channel that admits Na+ ions or both Na+ and 
K+ ions. These non-voltage-gated ion channels can be part of the receptor 
protein or can be a separate protein that opens in response to a 
cytosolic signal generated by the activated receptor. Channel opening 
leads to depolarization of the postsynaptic plasma membrane, promoting 
generation of an action potential. In contrast, binding of a 
neurotransmitter to an inhibitory receptor on the postsynaptic cell 
causes opening of K+ or Cl- channels. The resulting membrane 
hyperpolarization inhibits generation of an action potential in the 
postsynaptic cell."

How does one neuron "decide" while the brain is growing that a certain 
receptor should open K+ channels while another neuron decides the exact 
same receptor should open Na+ channels?  Is it completely random, but 
doesn't affect the brain because the inherent plasticity makes up for it?  
Or is there some order that defines which neurons do what?

Lastly, how long do neurotransmitters generally stay in a synapse before 
reuptake or broken down by enzymes?

Thanks again, sorry for the barrage of questions.  If there is a book or 
web-resource that you want to point me towards instead, that's just fine.  
I have access to my university library, but trying to figure out which 
book is helpful to my particular questions is frustrating at best.

-Zachary Tong

"John H." <j_hasenkam At yahoo.com.au> wrote in
news:1167832816.678362.224090 At i12g2000cwa.googlegroups.com: 

> Very vaguely Peter, my memory on this is not clear, but I think there
> were some news reports a few years indicating that neurons can "switch
> careers"; though this was only during embryonic development. so I
> looked
> Extract
> Other examples of two fast neurotransmitters released from the same
> neuron include GABA and glycine in interneurons of the spinal cord (5)
> and glutamate and dopamine in ventral midbrain dopamine neurons (6).
> Of all CNS neurons, the granule cells of the dentate gyrus appear to
> be the champions of neurotransmitter colocalization: glutamate,
> enkephalin, dynorphin, zinc, and finally GABA (2)(
> ---
> Trick was to search for "single neuron" AND neurotransmitter. Stop
> making me  think dude, it's been a long day and I'm tired.
> Shall we sing a lament for the poms?. They are not taking those Ashes
> back dude. I'll brain the bastards if they do!!!
> Be well,
> John.
> Epilepsy Curr. 2002 Sep;2(5):143-145. Related Articles, Links
> The GAD-given Right of Dentate Gyrus Granule Cells to Become
> GABAergic. 
> Mody I.
> Departments of Neurology and Physiology, The David Geffen School of
> Medicine, UCLA, Los Angeles, California.
> looked into the past, and the other, into the future. Do neurons
> possess a Janus face when it comes to neurotransmitters, or a given
> neuron is to be forever solely gamma-aminobutyric acid (GABA) ergic,
> glutamatergic, dopaminergic, peptidergic, or
> YOURPREFERREDTRANSMITTERergic? The answer is that the terminals of
> many neurons are homes to even more than two neurotransmitters. All
> this in spite of the "one neuron-one transmitter" usual
> misinterpretation of Sir Henry Hallett Dale's postulate, originally
> meant to indicate that a metabolic process taking place in the cell
> body can influence all processes of the same neuron. A large variety
> of neurons in the CNS, many of them GABAergic, produce and release
> chemicals that satisfy some of the criteria used to define
> neurotransmitters. The usual scenario for a dual-transmitter terminal
> is that the fast-acting transmitter such as GABA or glutamate is
> stored in regular synaptic vesicles, whereas a neuropeptide is stored
> in dense core vesicles (1). The vesicular zinc found in many
> glutamatergic terminals also may be considered to be a second
> neurotransmitter, based on its vesicular packaging with the aid of a
> specific vesicular transporter, and its postsynaptic actions through
> high-affinity binding sites and permeation through certain channels
> (2). Whenever a "fast" and a "slow" neurotransmitter are present in
> the same presynaptic terminal, it is customary to assume that their
> release can be differentially regulated (1). There is little
> convincing experimental support for this phenomenon in the mammalian
> CNS. The coexistence of two "fast" neurotransmitters in the same
> terminal is less frequent, but not unheard of. In neonatal sympathetic
> neurons cocultured with cardiac myocytes, norepinephrine and
> acetylcholine coexist and have opposite actions on the cardiac muscle
> cells (3). Very recently we learned that brain-derived neurotrophic
> factor acting at the low-affinity neurotrophin receptor p75(NTR),
> perhaps as part of a programmed developmental switch, can convert the
> phenotype of the sympathetic neuron from noradrenergic to cholinergic
> (4). Other examples of two fast neurotransmitters released from the
> same neuron include GABA and glycine in interneurons of the spinal
> cord (5) and glutamate and dopamine in ventral midbrain dopamine
> neurons (6). Of all CNS neurons, the granule cells of the dentate
> gyrus appear to be the champions of neurotransmitter colocalization:
> glutamate, enkephalin, dynorphin, zinc, and finally GABA (2)(7)(8)(9).
> With this many transmitters in a single neuron, there are probably
> different ways in which they can be released. Dynorphin and other
> opioid peptides can be released directly from the dendrites to inhibit
> excitatory transmission (8). A similar mechanism may take place for
> GABA, as described in cortical GABAergic neurons (10).
> PMID: 15309121 [PubMed - as supplied by publisher]
> Entertained by my own EIMC wrote:
>> I *hypothesize* (or speculate) the existence (or is it already
>> known?) of neurons that release one type of transmitter when firing
>> for a relatively short time but a different transmitter after a while
>> when firing persistently for a relatively long time (or perhaps that
>> after a while of persistent firing release 'the last' transmitter at
>> a higher ration to 'the first').
>> Please confirm or debunk as appropriate!
>> P

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