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A Theory of Neuropeptides?

k p Collins kpaulc at [----------]earthlink.net
Thu Jan 8 04:53:58 EST 2004


Hi Dag,

"Dag Stenberg" <dag.stenberg at nospam.helsinki.fi.invalid> wrote in message
news:bth7nq$bjm$1 at oravannahka.helsinki.fi...
> k p  Collins <kpaulc@[----------]earthlink.net> wrote:
> > "yan king yin" <y.k.y at lycos.com> wrote in message
> > news:72de81ae.0401060226.67da0596 at posting.google.com...
> >> Neuropeptides (when they're located at the pre-synapse) are usually
> >> secreted after intense stimulation such as tetanic trains. ...
> >
> > There's an easy first-test with respect to this question - assay
> > peptide concentrations before and after episodes of sleeping
> > consciousness [because, if your hypothesis is valid, then the
> > 'catching-up' would be most-easily handled during sleeping-
> > consciousness. And, since it's easy to look at before-and-
> > after-sleep peptide concentrations [well, relatively-easy, all
> > things considered], checking that out would be a good first
> > 'step' to take with respect to your hypothesis.
>
> Ken, do you mean "sleep" by "sleeping consciousness"? Or do you mean
> "REM sleep"? Or do you mean "across the sleep-wake cycle"?

I was refering to looking for a difference before and after =any= sleep.

And I was discussing with specific respect to the possibility that,
if peptides play a role in "information overload", then it's probable
that that would constitute a sort of 'workload queing' with respect
to processing that occurs during sleep - that the "information overload",
somehow 'represented' in the formation of a 'peptide-response' to
"information overload", would actually get sorted-out during sleep.

As I've discussed in the past, it's my position that a lot of this sort
of thing does happen during sleep - with respect to "experiential total"
cross-correlation, which is absolutely-necessary with respect to
maintaining 'normal', unified waking-consciousness - simply be-
cause, during waking-consciousness, one's neural activation is
necessarily [more or less] specifically-correlated to one's then-
occurring experience, but cross-experiential-total cross-correlation
of each 'day's new experience is =absolutely-necessary= if a
unified consciousness is, in fact, to be maintained.

As a Programmer, it's easy for me to see that the sleep cycle's
variable-duration "staging" constitutes a mechanism that is perfectly-
suited to 'walking' one's experiential-total [the totality of one's
'memory'] and cross-correlating ['consolidating'] the day's ex-
perience with respect to all of one's experience.

I think this is why sleep is necessary, and is why we do, in fact,
sleep.

It's be-cause we cannot keep everything we've ever experienced
in-mind during waking-consciousness. That would be so 'distracting'
that it would be anti-survival.

But it's absolutely necessary that the experiential-total cross-correlation
occur.

So, we sleep, and the very-active 'states' of sleeping-consciousness,
with their periodic cycling, in which cycles grow shorter as the
overall sleep 'cycle'  procedes, is flat-out a 'picture' of computerized
database "reorganizations" [that, BTW, occur for the very 'same' reason,
only with respect to shortening data pointer chains that have grown
overly-long, or [through multiple deletions, restores, modifications, etc.]
overly-convoluted, which can greatly impact database performance.

The computer 'consolidation' ["reorganization"] process occurs in a
non-information-content-relevant way that's analogous to the informa-
tion-content relevant way that whole-experiential-total 'consolidation'
occurs within nervous systems during sleep.

It was out of my awareness of these sleeping-consciousness whole-
experiential-total 'consolidation' dynamics that I suggested that the
poster look for a sleep-correlated differential.

More below.

>
> Anyway, there are publications since 1909 attempting to assay protein or
> peptide concentrations after prolonged waking in comparison with the
> well-slept state, or differences between sleep and waking. Of course, in
> 1909 they could not identify the peptides, but they found that a
> protein-based substance accumulated in the brains of sleep-deprived
> animals would induce sleep when infused into the cerebroventricular
> system of other animals. About 1975, the accumulation of muramyl peptide
> during prolonged waking was observed. It was later found to relate to
> and cause the production of interleukin-1 during waking, and indeed it
> has been found that prolonged waking induces the transcription by
> the interleukine-1 gene.
>   Several other genes are transcribed more intensely during waking than
> during sleep. It follows that their gene products (proteins eventually
> broken down to peptides, which may be directly involved in transmission or
> more indirectly, by affecting the regulation of cellular functions) may
also
> vary with the sleep-wake state. Most of these genes are immediate early
genes
> or gene products related to synaptic plasticity or cellular metabolism. A
> very few genes are transcribed more during sleep.
>
> Thoughts about peptides related to sleep homeostasis can be divided into
> the depletion hypotheses and the accumulation hypotheses. Does waking
> activity deplete something useful and necessary, or does it accumulated
something
> harmful (the hypnotoxin theory)?
>
> If levels of a peptide increases during wakefulness, it might mean that
its use
> is diminished, or alternatively, that its production is increased. This
> latter may be due to increased gene transctiption, and may be a
> compensatory phenomenon because of increased use. If a peptide
> decreases during wakefulness, it might mean that it is used more and it
> is being depleted, or that its production has simply become decreased.
> If one samples the level during a longer period of wakefulness, one might
> see initial depletion followed by compensatorily increased production. A
> single time point may produce misleading results. Furthermore, study
> during spontaneously oscillating sleep-wake cycles may not reveal the
> true dependence on wake and sleep, as there may be a delay between the
> change in state and the concentration changes. If the delay is due to
> changes secretion from stores in the presynaptic terminal, these
> concentration changes are seen with short delay; if the change involves
> gene transcription, the change occurs with a delay of hours to days, and
> cannot be analyzed by studying spontaneous sleep-wake patterns (with a
> cycle of 24h in humans and even less than an hour in most other
vertebrates.

Thank you for this Generous sharing of your Expertise, Dag.

> So when Ken writes "There's an easy first-test with respect to this
> question" it is not all that easy. In fact, a great deal of peptide
> assay has been done during the last few decades in relation to sleep and
> wake, and there is still no easy answer.

I'm sorry, but my personal experience leads me to [gently] disagree.

Because I'm always hard-pressed to feed and shelter myself [for decades],
when I have the $ resources to work on my research, I do so by working
for as long as I can - to cram as much into the ol' noggin' lab as I can be-
fore allowing myself to sleep.

As a result, my sleep cycle gradually rotates 'around the clock'.

As you can imagine, because I've been at this for so long, I've become
aware that there are several 'sub-processes' within sleeping-consciousness.

They are recognizable because they go in and out of sync, stereotypically,
as I allow my sleep cycle to rotate 'around the clock'.

So I can say, with Certainty, that if you find a subject who will endure
an analogous waking-sleeping discipline, you'll see periodic fluctuations
that correlate to these sleep sub-processes - and because they sort of
'slide-over' one another [they each 'go their own way'], the correlations
will be 'easy' to identify in pharmocological assays. [Whoops! I =don't=
know if such studies can be done in Humans - probably not, eh? Or do
the substances you monitor occur, say, in bodily fluids? It's problematical
if your work is invasive. That would mean that you'd have to force the
'around the clock' sleep cycle rotation upon animal subjects - which intro-
duces a variable that is not within my experience, because I do this stuff
volitionally - in order to =relieve= the 'stress' with respect to unanswered
questions.

You know - "information overload" :-]

All that I've discussed was in why I responded to the prior post.

I wanted to get into this discussion with someone.

So, Thank You, Dag.

I'll save your informative post special, so I can have ready access
to it when I get back to reading in Neuroscience [if I ever will].

I'll come over there and let your team 'wire me up' if you want to see the
sleep-sub-process cycling that I've discussed.

I'm so used to it that I usually don't even pay any attention to it, other
than knowing, from it, when it's best to go to bed [when I should go
to bed in order to get the best-sleep that's possible].

[I've also done a lot of 'experiments' with respect to information-retention
and my many diferent sleep-cycle routines. "Never waste data!" is a 'motto'
that I Live by :-]

Cheers, Dag,

ken [k. p. collins]





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