Question



K

Kola9809

Guest
Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
mechanism is that the photic stimuli (which do not per se activate any gene) are received in retinal
neurons, converted into electrical signals that are processed (and alternatively transformed into
chemical-electrical signals) in a neural circuit involving neurons of the superior cervical
ganglion, intermediolateral nucleus of the upper thoracal spinal cord, hypothalamic paraventricular
nucleus, suprachiasmatic nucleus, until it reaches the pineal gland cells where the chemical output
of the circuit activates genes involved in the synthesis of melatonin.

My question is: Since the activation of those genes is not a random process, it requires
information. Where does that information come from? Is this the kind of information that Richard
Lewontin believes is necessary for the expression of genetic information?

Kola 9809
 
On Sun, 1 Feb 2004 18:46:19 +0000 (UTC), [email protected] (Kola9809)
wrote:

>Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
>mechanism is that the photic stimuli (which do not per se activate any gene) are received in
>retinal neurons, converted into electrical signals that are processed (and alternatively
>transformed into chemical-electrical signals) in a neural circuit involving neurons of the superior
>cervical ganglion, intermediolateral nucleus of the upper thoracal spinal cord, hypothalamic
>paraventricular nucleus, suprachiasmatic nucleus, until it reaches the pineal gland cells where the
>chemical output of the circuit activates genes involved in the synthesis of melatonin.
>
>My question is: Since the activation of those genes is not a random process, it requires
>information. Where does that information come from? Is this the kind of information that Richard
>Lewontin believes is necessary for the expression of genetic information?
>
>
I don't quite understand what you mean by "the activation of genes ... requires information." It is
trivial for nerve activity to cause gland secretion. It is aso well known that nerve activity can
result in changes in gene transcription. The key is the notion of metabotrophic synapses that
activate 2nd messenger systems like G-proteins and cAMP. These, acting through protein kinases, can
easily do all sorts of things to cells including cause secretion or, through the action of CREB
(cAMP response element binding sites), activate genes. There are many other pathways by which this
can happen.
 
[email protected] (Kola9809)
>wrote:
>
>>Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
>>mechanism is that the photic stimuli (which do not per se activate any gene) are received in
>>retinal neurons, converted into
>electrical
>>signals that are processed (and alternatively transformed into chemical-electrical signals) in a
>>neural circuit involving neurons of the superior cervical ganglion, intermediolateral nucleus of
>>the upper thoracal spinal cord, hypothalamic paraventricular nucleus, suprachiasmatic nucleus,
>>until it reaches the pineal gland cells where the chemical output of the circuit activates genes
>>involved in the synthesis of melatonin.
>>
>>My question is: Since the activation of those genes is not a random process,
>it
>>requires information. Where does that information come from? Is this the
>kind
>>of information that Richard Lewontin believes is necessary for the
>expression
>>of genetic information?
>>
>>
>I don't quite understand what you mean by "the activation of genes ... requires information."

Thank you for responding to my question and I hope your obvious expertise could be illuminating.

I apoplogize for not being more explicit in formulating my question. Let me try once again. I wrote:
"Since the activation of those genes is not a random process, it requires information."

My premise is that for a process to happen systematically, specific information is needed. In our
case, extracellular information (chemical signals) need to be provided to the pineal cells for
activating genes involved in the synthesis of melatonin. This is why no other type of cell in the
body does activate those genes. I will break down my question by trying to explain "Why?" the
information for activation of melatonin genes is necessary, as well as "Where?" and "How?" is it
generated.

Why is information for activation of melatonin genes necessary? Pineal cells are uniquely capable of
activating those genes and synthesizing melatonin. The reason is that only those cells receive the
necessary information, i.e. chemical signals from the suprachiasmatic neurons. Having exactly the
same set of genes, the rest of the body cells do not activate those genes because they do not
receive that information. I believe we all agree on this.

Where does this information for activating melatonin genes in the pineal cells come from? The
suprachiasmatic signal itself is the chemical output of processing in the above-mentioned circuit of
the electrical signal into which retinal neurons have converted an external stimulus, the day-night
(circadian) cycle. This conversion as well, is not a random process, but very specific and results
from a computational process taking place in those neurons. It turns an otherwise neutral stimulus
intu a cue, an instruction for activating a signal cascade that leads to specific gene activation
for an adaptive phenotypic result. The processing takes place in the above mentioned neural circuit
and it is the neural circuit that generates the information. Correct me if I'm wrong.

How is this information generated in neural circuits? Experimental evidence shows that the chemical
output, or information for activating genes in neurons is generated computationally, by processing
internal and external stimuli according to a general model that essentially comprises: -reception of
internal/external signals by interoceptors/exteroceptors, -conversion of those stimuli into specific
patterns of electrical signals, -reconfiguration of synaptic morphology of the neural circuit and
resulting change in the computational properties of the circuit, which
- changes the electrical/chemical output of the circuit, leading to
- specific activation/inactivation of target genes in neurons.

I hope I have clarified the meaning of my sentence on the information necessary for
activation of genes.

>It is trivial for nerve activity to cause gland secretion. It is aso well known that nerve activity
>can result in changes in gene transcription. The key is the notion of metabotrophic synapses that
>activate 2nd messenger systems like G-proteins and cAMP.

Being trivial doesn't mean it is explained or selfevident. Your talk about 2nd messenger systems
implies the extracellular messages (=information) computationally generated in and coming from
neural circuits.
 
On Tue, 3 Feb 2004 18:47:32 +0000 (UTC), [email protected] (Kola9809)
wrote:

>My premise is that for a process to happen systematically, specific information is needed. In our
>case, extracellular information (chemical signals) need to be provided to the pineal cells for
>activating genes involved in the synthesis of melatonin. This is why no other type of cell in the
>body does activate those genes. I will break down my question by trying to explain "Why?" the
>information for activation of melatonin genes is necessary, as well as "Where?" and "How?" is it
>generated.
>
>Why is information for activation of melatonin genes necessary? Pineal cells are uniquely capable
>of activating those genes and synthesizing melatonin. The reason is that only those cells receive
>the necessary information, i.e. chemical signals from the suprachiasmatic neurons. Having exactly
>the same set of genes, the rest of the body cells do not activate those genes because they do not
>receive that information. I believe we all agree on this.
>
>Where does this information for activating melatonin genes in the pineal cells come from? The
>suprachiasmatic signal itself is the chemical output of processing in the above-mentioned
>circuit of the electrical signal into which retinal neurons have converted an external stimulus,
>the day-night (circadian) cycle. This conversion as well, is not a random process, but very
>specific and results from a computational process taking place in those neurons. It turns an
>otherwise neutral stimulus intu a cue, an instruction for activating a signal cascade that leads
>to specific gene activation for an adaptive phenotypic result. The processing takes place in the
>above mentioned neural circuit and it is the neural circuit that generates the information.
>Correct me if I'm wrong.
>
>How is this information generated in neural circuits? Experimental evidence shows that the chemical
>output, or information for activating genes in neurons is generated computationally, by processing
>internal and external stimuli according to a general model that essentially comprises: -reception
>of internal/external signals by interoceptors/exteroceptors, -conversion of those stimuli into
>specific patterns of electrical signals, -reconfiguration of synaptic morphology of the neural
>circuit and resulting change in the computational properties of the circuit, which
>- changes the electrical/chemical output of the circuit, leading to
>- specific activation/inactivation of target genes in neurons.
>
>I hope I have clarified the meaning of my sentence on the information necessary for activation
>of genes.
>

There are many ways that the informal notion of "information" can be expressed. First, there is a
specific nervous pathway from the visual system through the brain to the pineal gland. That consists
of specific cells growing axons in certain specific directions but not in others and forming
synaptic connections with certain specific cells but not with others. In addition, there are ways in
which nerve cells form many contacts with many cells but somehow experience trims down most of the
connections to leave only certain ones remaining. There is "information" involved in all these
choices. We do know many things about trophic factors and cell recognition proteins that assist in
making specific neuronal connections, but do not know the whole story in most cases. The pathway
leading from the eye to the pineal is no more involved or complicated than any other "specified" or
"determined" neural pathway -- the visual system, the auditory system, the limbic system, etc. These
all involve specific connections between specific neuron types.

Once the pathway is made, there is another form of "information", the presence of absence of the
light signal. But that is trivial. Light and dark change the activity of cells in the visual pathway
which changes the activity of cells connecting to the pineal which changes the level of response in
the pineal gland cells. This form of information is the traditional notion of what nervous systems
do -- process and transmit information in the form of electrical signals.

Finally, there is "information" is the cell signaling machinery whereby synaptic activation of
pineal gland cells activates specific cell processes leading to the production and release of
melatonin orthe activation an inactivation of the genes involved in melatonin synthesis. This is no
different from the fact that the cell signaling machinery in a pancreatic beta cell causes insulin
secretion or the cell signaling machinery in a muscle cell causes contraction.

So there are three kinds (at least) of information involved -- specificity of nerve pathways,
neuronal signals, and cell responses to stimulation. Each of these is known in many details.

Where does all this "information" come from? These pathways seem to be genetically coded in the same
way that the knee-jerk reflex is genetically coded. There is a tremendous amount of research on just
how genetic information can produce specific nerve circuits. Many invertebrates have individually
identifiable and genetically determined neurons that have very specific functions in producing and
controlling behavior. The roundworm, Caenorhabditis elegans, is the ultimate example since every
individual worm in the species, except for mutations, has exactly the same number of cells in their
body, The cells form in exactly the same way from the fertilized egg, are located in exactly the
same location, and do exactly the same thing. The genome is completely known and their is a major
research effort in working out how all this really works.

Where does the genetic "information" come from? That is what evolution is all about.
 
Kola9809 <[email protected]> wrote or quoted:

> Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
> mechanism is that the photic stimuli (which do not per se activate any gene) are received in
> retinal neurons, converted into electrical signals that are processed (and alternatively
> transformed into chemical-electrical signals) in a neural circuit involving neurons of the
> superior cervical ganglion, intermediolateral nucleus of the upper thoracal spinal cord,
> hypothalamic paraventricular nucleus, suprachiasmatic nucleus, until it reaches the pineal gland
> cells where the chemical output of the circuit activates genes involved in the synthesis of
> melatonin.
>
> My question is: Since the activation of those genes is not a random process, it requires
> information. Where does that information come from?

>From the environment.
--
__________
|im |yler http://timtyler.org/ [email protected] Remove lock to reply.
 
>On Thu, 5 Feb 2004 06:17:36 +0000 (UTC)Tim Tyler wrote:

>Kola9809 <[email protected]> wrote or quoted:
>
>> Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
>> mechanism is that the photic stimuli (which do not per
>se
>> activate any gene) are received in retinal neurons, converted into
>electrical
>> signals that are processed (and alternatively transformed into chemical-electrical signals) in a
>> neural circuit involving neurons of the superior cervical ganglion, intermediolateral nucleus of
>> the upper thoracal spinal cord, hypothalamic paraventricular nucleus, suprachiasmatic nucleus,
>> until it reaches the pineal gland cells where the chemical output of the circuit activates genes
>> involved in the synthesis of melatonin.
>>
>> My question is: Since the activation of those genes is not a random process, it requires
>> information. Where does that information come from?
>
>>From the environment.
>--
>__________
> |im |yler http://timtyler.org/ [email protected] Remove lock to reply.
>

If that information is the environmental stimulus (which you seem to imply) skin cells that are in
direct contact with it would produce melatonin as well. But, as you know, they can not while pineal
cells with the same set of genes, do? And the reason is that only (!) pineal cells receive the
information on the stimulus (but not the stimulus itself).

Nevertheless, you may be be right and I - wrong. But, could you elaborate.

As all we know, the pineal cells do not receive the stimulus (day-night cycles); they are invariably
in darkness. That stimulus is received by retinal neurons (they, nevertheless do not produce
melatonin), which code it in the form of specific electrical signals (this is the information on the
nature of the stimulus). But this information still is not "intelligible" to genes. This is why it
is once more processed in the complex melatonin circuit, which releases a chemical signal that via
signal transduction pathways affects the expression of genes responsible for melatonin synthesis in
pineal cells.

I'm openminded to listen and change my opinion.
 
Kola9809 <[email protected]> wrote or quoted:
> >On Thu, 5 Feb 2004 06:17:36 +0000 (UTC)Tim Tyler wrote: Kola9809 <[email protected]> wrote:

> >> Pineal gland cells produce melatonin in response to day-night cycles. The generally accepted
> >> mechanism is that the photic stimuli (which do not per se activate any gene) are received in
> >> retinal neurons, converted into electrical signals that are processed (and alternatively
> >> transformed into chemical-electrical signals) in a neural circuit involving neurons of the
> >> superior cervical ganglion, intermediolateral nucleus of the upper thoracal spinal cord,
> >> hypothalamic paraventricular nucleus, suprachiasmatic nucleus, until it reaches the pineal
> >> gland cells where the chemical output of the circuit activates genes involved in the synthesis
> >> of melatonin.
> >>
> >> My question is: Since the activation of those genes is not a random process, it requires
> >> information. Where does that information come from?
> >
> >>From the environment.
>
> If that information is the environmental stimulus (which you seem to imply) skin cells that are in
> direct contact with it would produce melatonin as well. But, as you know, they can not while
> pineal cells with the same set of genes, do? And the reason is that only (!) pineal cells receive
> the information on the stimulus (but not the stimulus itself).
>
> Nevertheless, you may be be right and I - wrong. But, could you elaborate.
>
> As all we know, the pineal cells do not receive the stimulus (day-night cycles); they are
> invariably in darkness. That stimulus is received by retinal neurons (they, nevertheless do not
> produce melatonin), which code it in the form of specific electrical signals (this is the
> information on the nature of the stimulus). But this information still is not "intelligible" to
> genes. This is why it is once more processed in the complex melatonin circuit, which releases a
> chemical signal that via signal transduction pathways affects the expression of genes responsible
> for melatonin synthesis in pineal cells.
>
> I'm openminded to listen and change my opinion.

This is like me saying that your friend's voice on the telephone comes from your friend - and then
you arguing that it is actually coming from the speaker in the telephone handset.
--
__________
|im |yler http://timtyler.org/ [email protected] Remove lock to reply.
 
On Fri, 6 Feb 2004 02:04:56 +0000 (UTC), [email protected] (Kola9809)
wrote:

>
>
>On Wed, 4 Feb 2004 06:18:25 +0000 (UTC) r norman wrote:
>
>>(Kola9809) wrote:
>
>>>I will break down my question by trying to explain "Why?" the information
>>for
>>>activation of melatonin genes is necessary, as well as "Where?" and "How?"
>>is
>>>it generated.
>
>(I apologize for trying to summarize and not reproduce here our previous discussion in their
>entirety.)
>
>While it seems that both of us agree on the first question, as far as the second question goes:
>"Where does this information for activating melatonin genes in the pineal come from" my
>explanation was:
>
>>>The suprachiasmatic signal itself is the chemical output of processing in
>>the
>>>above-mentioned circuit of the electrical signal into which retinal neurons have converted an
>>>external stimulus, the day-night (circadian) cycle. This conversion as well, is not a random
>>>process, but very specific and
>>results
>>>from a computational process taking place in those neurons. It turns an otherwise neutral
>>>stimulus intu a cue, an instruction for activating a
>>signal
>>>cascade that leads to specific gene activation for an adaptive phenotypic result. The processing
>>>takes place in the above mentioned neural circuit and it is
>>the
>>>neural circuit that generates the information. Correct me if I'm wrong.
>
>Even though you neither directly address that question nor express any reservations on my response,
>you argue:
>
>>So there are three kinds (at least) of information involved -- specificity of nerve pathways,
>>neuronal signals, and cell responses to stimulation. Each of these is known in many details.
>
>Even though I would consider the above elements of an "information channel" rather than proper
>information, if I got it right, your statement implies that not one but three types of epigenetic
>information are necessary for expression of genes in the CNS ("specificity of the nerve pathways,
>neuronal signals, and cell responses" are clearly not genetic information; only the sequence of
>nucleotides in the DNA is).
>
>As for the third question on how this epigenetic information is generated in the neural circuits,
>my response was:
>
>>>Experimental evidence shows that the chemical output, or information for activating genes in
>>>neurons is generated computationally, by processing internal and external stimuli according to a
>>>general model that essentially comprises: -reception of internal/external signals by
>>>interoceptors/exteroceptors, -conversion of those stimuli into specific patterns of electrical
>>>signals, -reconfiguration of synaptic morphology of the neural circuit and resulting change in
>>>the computational properties of the circuit, which changes the electrical/chemical output of the
>>>circuit, leading to
>>>- specific activation/inactivation of target genes in neurons.
>>>
>
>Even though you do not address this question, I am indeed very interested to know your expert
>opinion on whether the above epigenetic mechanism is real or supported by neurobiological data.
>
Again I have trouble following your logic because I think we are not thinking at all on the
same line.

My impression is that you somehow think that there is a neural code that tells a pineal cell
"activate a melatonin gene" as opposed to a different code that tells a pineal cell to do something
else. In other words, somehow the neural circuit has to figure out (compute) somehow just how to
code a signal to activate a gene.

That is not the way it works. When a melatonin secreting cell in the pineal receives a nerve signal,
any nerve signal, it secretes melatonin and, if appropriate, also activates whatever genes are
necessary to synthesize melatonin. That is simply the nature of the cell.

When a muscle cell receives a nerve signal, it contracts. When a gland cell receives a nerve signal,
it secretes. That is simply the way those cells are built. There is nothing special about the
message. Any old message will do. That is, any message using the same nerve transmitter and
activating the same synaptic receptors.
 
On Sat, 7 Feb 2004 05:52:56 +0000 (UTC), [email protected] (CNCabej)
wrote:

>On Fri, 6 Feb 2004 16:36:06 +0000 (UTC)
>
>Tim Tyler wrote:>> >Kola9809 <[email protected]> wrote:
>>
>>> >> Pineal gland cells produce melatonin in response to day-night cycles.
>>The
>>> >> generally accepted mechanism is that the photic stimuli (which do not per se activate any
>>> >> gene) are received in retinal neurons, converted into electrical signals that are processed
>>> >> (and alternatively transformed into chemical-electrical signals) in a neural circuit
>>> >> involving neurons of the superior cervical ganglion, intermediolateral nucleus of the upper
>>> >> thoracal spinal cord, hypothalamic paraventricular nucleus, suprachiasmatic nucleus, until it
>>> >> reaches the pineal gland cells where the chemical output of the circuit activates genes
>>> >> involved in the synthesis of melatonin.
>>> >>
>>> >> My question is: Since the activation of those genes is not a random process, it requires
>>> >> information. Where does that information come from?
>>> >
>>> >>From the environment.
>>>
>>> If that information is the environmental stimulus (which you seem to imply) skin cells that are
>>> in direct contact with it would produce melatonin as
>>well.
>>> But, as you know, they can not while pineal cells with the same set of
>>genes,
>>> do? And the reason is that only (!) pineal cells receive the information on
>>the
>>> stimulus (but not the stimulus itself).
>>>
>>> Nevertheless, you may be be right and I - wrong. But, could you elaborate.
>>>
>>> As all we know, the pineal cells do not receive the stimulus (day-night cycles); they are
>>> invariably in darkness. That stimulus is received by
>>retinal
>>> neurons (they, nevertheless do not produce melatonin), which code it in the form of specific
>>> electrical signals (this is the information on the nature
>>of
>>> the stimulus). But this information still is not "intelligible" to genes.
>>This
>>> is why it is once more processed in the complex melatonin circuit, which releases a chemical
>>> signal that via signal transduction pathways affects
>>the
>>> expression of genes responsible for melatonin synthesis in pineal cells.
>>>
>>> I'm openminded to listen and change my opinion.
>>
>>This is like me saying that your friend's voice on the telephone comes from your friend - and then
>>you arguing that it is actually coming from the speaker in the telephone handset.
>>--
>
>Let's get serious. I am very interested in discussing this topic. Do you really think that
>information from the environment regulates the function of our genes ?
>
>If information implies a sender and a receiver, do you believe that the environment is the
>sender and genes are the receivers of environmental information? Can you substantiate this
>Lamarckian concept?
>
>As I have pointed out earlier, I see this differently. A piece of information from the environment
>would be used by genes only if it is "intelligible" to them, but the circadian cycle (the sun
>light or the lack of it) is not. Neither the sun light nor the darkness are able to
>activate/inactivate any gene. This is the reason why the stimulus is received and converted into
>an electrical signal (=information) and further processed in the melatonin neural circuit which
>generates the chemical signal (=information) that is intelligible to the gene as the "receiver".
>It is not the external stimulus per se, but the chemical output (=information) generated by
>processing of the stimulus in the neural circuit that via the respective transduction pathways
>reaches the genes responsible for the synthesis of melatonin, that is intelligible to (i.e.
>contains information for) activating those genes. This information generated in the neural circuit
>is processing-dependent, hence epigenetic; it does not exist but it is computationally generated
>in response to external/internal stimuli.
>
>Let me try an analogy from linguistics (my hobby). When I spell the Messapian (an ancient
>indoeuropean language spoken in southern Italy more than 2 thousand years ago) word "bila" it
>conveys no information to you as a receiver, although it did for the Messapians. Now, I make it
>intelligible to you by translating it into the English word "daughter". Similarly, the neural
>circuits "translate" the external stimulus, which is "senseless" to genes, into a specific
>epigenetic information for their activation/inactivation.
>
>Do you agree? I wait for your input.
>

I still think that "information translation" is not a proper way of looking at the situation.

Light entering the eye causes genes to be expressed in specific cells. There are a lot of
intermediate steps, but there is a demonstrable chain of cause-and-effect events that can be
described linking stimulus to response. It is not necessary to talk in terms of information
generation, merely in terms of "event A causes event B causes event C causes event D causes .....
causes event Z. Light in a rod or cone cell is translated into electrical potential, but that
involves a whole series of intermediate steps. Changes in electrical potential in rod and cone cells
in the retina cause release of synaptic transmitter onto melatonin secreting cells in the pineal,
but that involves a whole series of intermediate steps. Synaptic transmitter binding to receptors on
melatonin secreting cells in the pineal activate genes in the cell nucleus, but that involves a
whole series of intermediate steps.

The problem is one of cell physiology, not of information translation.
 
CNCabej <[email protected]> wrote or quoted:

> Do you really think that information from the environment regulates the function of our genes ?

Of course.

> Can you substantiate this Lamarckian concept?

It is not especially Lamarckian - since it doesn't involve acquired traits being inherited.

The environment coming to affect gene expression - and even the inheritance of genes - is old news -
see "The Baldwin Effect".
--
__________
|im |yler http://timtyler.org/ [email protected] Remove lock to reply.
 
> > >> My question is: Since the activation of those genes is not a random process, it requires
> > >> information. Where does that information come from?

Good question! How do we find meaning in anything?
 
[email protected] (CNCabej) wrote in
news:[email protected]:

> On>Tue, 10 Feb 2004 00:14:44 +0000 (UTC) >Tim Tyler tim@tt1lock.
> wrote:

>>The environment coming to affect gene expression - and even the inheritance of genes - is old news
>>- see "The Baldwin Effect".

> Sorry, but my question was neither the one you "quote" nor related to "The environment coming to
> affect gene expression - and even the inheritance of genes." My question was essentially
> different: "If information implies a sender and a receiver, do you believe that the environment is
> the sender and genes are the receivers of environmental information?" "Can you substantiate this
> Lamarckian concept?"

I don't think this idea is all that controversial. A good book on the subject is "The Dependent
Gene", by David Moore, who gives numerous examples of how gene expression relies on environmental
cues (information if you will) for proper development. It is of course well known that the proper
contents of the cytoplasm of the ova are essential for normal development. The social insects are
replete with examples of how external influences determine the caste of the larva. IIRC, there
are several

changes in the environment.

Yours,

Bill Morse