On 17 Feb 2004 r norman wrote:

>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.
>
R. N.
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.

N.C.

First, I am glad we agree that a transfer of information generated in a  
specific circuit of the CNS is transmitted to the pineals cells. 
As for the nature of this information, it is essential to point out that

-this is different from the genetic information contained in genes in 
the form of nucleotide sequences determining the sequence of 
amino acids in RNA and polypeptides.

-the information that is sent to pineal cells does not preexist in the 
brain structure, but it is generated in the specific neural circuit, by 
processing the external stimulus. Being a result of a computational 
process (and having nothing to do with the sequence of nucleotides
in DNA), this is information is EPIGENETIC.

-this epigenetic information is necessary for expression of melatonin
genes in the pineal cells, i.e. controls their expression (in your expression,
the nervous system computes something like "tell the pineal to go" or
"don't tell the pineal to go")

I have difficulty in agreeing with you that "the neural information
coded simply "I got this stimulus". What does the target cell do with 
that information is totally irrelevant to the sensory system that 
detected the stimulus." 

This is indefensible in view of the facts that 
1) the neural circuit sends a "computed" signal that specifically
(not randomly) activates a specific signal transduction
pathway, which makes possible expression of melatonin genes.
At this point there is no choice for pineal cells; the expression of 
melatonin genes is unavoidable, predetermined by the epigenetic
information those cells receive.

2) The neural circuit not only generates the information for activation of 
melatonin genes, but it "knows"  to exactly address that 
information to a certain type of cell (out of more than 2 hundred cell types)
of a mammal), the only cells capable of producing melatonin, .

Finally, I am interested to know more about your idea that such information
transfer takes place in the developmental process.
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