On Mon, 16 Feb 2004 23:45:17 +0000 (UTC), cncabej{at}aol.com (CNCabej)
wrote:

>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.
>
We are still far apart but maybe converging.

Of course there is a sense of "information transfer" in all cell
signaling, including the binding of a hormone or neurotranmitter to
its receptor and the subsequent downstream pathway.  Of course there
is a sense of "information transfer" in the developmental process.

It was my impression that you were trying to say that somehow neural
circuits code "code information" for "turn on melatonin
synthesis".  I
am simply saying that the pattern of neural connectivity automatically
connects certain photosensitive cells to the sympathetic system.  The
nervous system computes something like "tell the pineal to go" or
"don't tell the pineal to go".  What the pineal does with that signal
(sympathetic activation) is something "coded" into the pineal gland,
not into neural computation.

Yes, CNS cells can express specific genes and they can be induced to
do so by stimuli or by hormones that never enter the CNS. Clearly what
happens is that such stimuli are acting on sense organs that send
action potentials into the CNS.  The post-synaptic signaling pathway
in specific CNS cells may well have the ability to activate genes --
the CREB system is a good example.  My impression was that you were
saying something like action potentials "code information" to
"activate this specific gene."  What I am saying is the the neural
information coded is simply "I got this stimulus".  What the target
cell does with that information is totally irrelevant to the sensory
system that detected the stimulus.
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