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. R.A. 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.