On Fri, 13 Feb 2004 16:49:38 +0000 (UTC), cncabej{at}aol.com (

>Let me try once again to show you the "conceptual" difference
between the
>classical way of gene expression and the expression of genes in neural
tissues?
>In the classical mode of gene expression, the effect of the stimulus is
>determined by stereochemical and thermodynamical properties of the stimulus
and
>the respective pathway. Unlike that, the activation/inactivation of genes in
>the CNS does not depend on the stereochemical and thermodynamical properties
of
>the stimulus but on the computational properties of the neural circuit that
>processes the stimulus: in response to the same external stimulus ( with the
>same stereochemical and thermodynamical properties) the CNS is able to
>manipulatively and adaptively activate different genes (examples bound). This
>does not happen anywhere else in the body. It is the  processing of the
>stimulus in neural circuits that makes possible
"manipulative" activation in
>the CNS of genes (such as melatonin and thyroxin you mention) that can't be
>activated in other types of cells. 
>
>You say that "All that happens is that a chemical binds to a receptor in the
>membrane of the thyroid or pineal gland cell and makes the cell "do its
>thing"". Unfortunately, this is neither "all" nor
the essential that happens.
>In both examples you see just the proximal link in a long cascade, ignoring
the
>series of signals  and especially the "essential" processing
of those stimuli
>(chill and darkness) in neural circuits, without which neither thyroxin nor
>melatonin is produced. You know better than me that chill applied to thyroid
>won't make it synthesize thyroxin (only hypothalamic TRH will, which in turn
is
>synthesized according to signals generated computationally by processing of
the
>stimulus in neural circuits in other parts of the brain). The same I have
>explained for melatonin synthesis. 
>
>What makes unique the thyroid in producing thyroxin and pineal in producing
>melatonin is the INFORMATION (computationally generated in neural circuits)
>they receive on the external stimulus (not the stimulus itself). Deprived of
>this INFORMATION generated in neural circuits, no other type of cell in the
>animal body is capable of synthesizing those chemicals.
>
>Is this manipulative (processing-dependent) activation/inactivation of genes
in
>the CNS requiring information ON THE STIMULUS "essentially different both in
>the  the mechanism that makes it possible and the outcome? 

I still think we are so far apart that we cannot understand each
other.  I have a great deal of difficulty with statements like "the
effect of the stimulus is determined by stereochemical and
thermodynamical properties of the stimulus" .

Let me try to be clear.  Pineal gland cells are highly differentiated
by whatever developmental processes produce those cells.  As a result,
they express the genes involved in melatonin synthesis and are capable
of secreting melatonin.   That is what I referred to as "their thing".
Neural computation has absolutely nothing to do with it. Other cells
express different genes and make different proteins and secretory
products.  When you stimulate a pineal gland cell, it "does its thing"
which is actually to secrete melatonin.  The computational properties
of neurons have nothing whatsoever to do with it.

In fact, the stmulation of the pineal is through the sympathetic
nervous system.  That is, if you drop norepinephrine onto the pineal
gland or artificially stimulate the superior cervical ganglion,  the
gland will release melatonin just as effectively as if you stopped
shining light into the eye.  The nervous system "calculates" only that
during daylight it should refrain from sending action potentials to
the superior cervical ganglion destined for the pineal and to resume
those action potentials during the night time.  Nowhere does the
nervous system calculate just how to activate any specific genes or
how to secrete any specific chemical.

NC

You write: "I have a great deal of difficulty with statements like
"the effect
of the
stimulus is determined by stereochemical and thermodynamical properties of 
the stimulus." Let me try to make it simpler . The spatial 
configuration of a hormone, and  an antibody molecule, must be 
complementary to that of a cell membrane receptor,and an antigen 
(this is a stereochemical property). But often this may be not sufficient
for two molecules to react, if they or  their environment do not 
possess enough energy that is necessary for that reaction to take place
(e.g., sequential phosphorylation of proteins in signal transduction pathways
is
necessary for activation of those pathways).

You also write: "Pineal gland cells are highly differentiated by whatever 
developmental processes produce those cells. As a result, they express
the genes involved in melatonin synthesis and are capable of secreting 
melatonin. That is what I referred to as "their thing"."  But, neither
the type of the cell nor  "the thing" tells us anything about the cause
of the expression of genes for melatonin genes in pineal cells 
(otherwise  I would expect you to elaborate on "why" the pineal cells do
what other cells can't). You can't explain an unknown with another.
If  we could automatically figure out causes and mechanisms of gene 
expression by the type of cell this would make unnecessary or 
obsolete one of the most important fields of modern biological research.

Further you write: "In fact, the stimulation of  the pineal is through
the sympathetic nervous system. That is, if you drop norepinephrine
onto the pineal gland or artificially stimulate the superior cervical ganglion,
the gland will release  melatonin just as effectively as if you stopped 
shining light into the eye." 
I am afraid that this contradicts your previous statements
(that no information is needed for expression of melatonin genes),
but I am glad to find something we agree on. If you drop epinephrine
or if you artificially stimulate the pineal cells to synthesize melatonin,
you are able to do this because you know,
you have information (in your expression you have "calculated") that
this will activate melatonin genes. A person that has no information
could not do it. Similarly, specific information is needed for specific 
activation of melatonin genes out of 30,000 genes in billions/trillions 
of more than 2 hundred types of cells of our body.

Now let me comment on your next and more encouraging statement.
You write "The nervous system "calculates" only that during daylight
it should refrain from sending action potentials to the superior cervical
ganglion destined for the pineal and to resume those action potentials." 
In principle, I agree completely with your ideas that
1. the nervous system controls both the activation and inactivation 
of melatonin genes,
2. that this CNS control is "calculated", in the meaning that the CNS knows
when to send and when to "refrain" from sending its signals for expression 
of genes for melatonin synthesis
Granted that a "calculated" response implies
"information", from the above 
premises anyone might draw the logical conclusion that the CNS is 
the source of the epigenetic information for melatonin synthesis.

But the last phrase shows that you still feel not comfortable with your above
statement. You write:"Nowhere does the nervous system calculate just how
to activate any specific genes or how to secrete any specific chemical."
I could bring numerous examples proving the contrary. For now let me just very
briefly state that the CNS can express genes that no extracerebral cells can.
It does
this by processing information on internal signals (hormones, growth factors)
which HAVE NO ACCESS to the CNS. For example, a stimulus on a drop in the 
level of estrogen in the blood is perceived and processed in a specific neural 
circuit. The chemical output of the processing (not the estrogen) of that
stimulus
via projections of the neurons of that circuit on specific hypothalamic cells
triggers
the expression of the GnRH (gonadotropin releasing hormone). This response is 
not determined by the stereochemical and thermodynamical properties but from
the processing (computational process) of the stimulus in the respective neural
circuit.
This is the reason why in nonneural cells the estrogen activates compeltely
different genes.

P.S. as for your statement that "computational properties of neurons have
nothing 
whatsoever to do with" the secretion of melatonin, this is hardly compatible
with the 
predominant opinion of researchers that CNS responses are determined by 
computational properties of respective neural circuits, and those properties
change
in response to various internal and external stimuli.
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