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Efferents for raphe nuclei

John H. johnh at faraway.xxx
Tue Apr 1 13:31:33 EST 2003


Peter,

1.

I fully concur with statement re the 'dots and dashes' of scientific
literature. It is extremely frustrating to often find thousands of research
pieces on this or that, often contradictory, with differing experimental
paradigms, with differing terms for the same molecule, and the all too
obvious information overload that in my opinion reflects a failure by the
scientific community to adopt a more organised approach in the way research
is conducted and collated into "meaningful wholes". Granted one is reluctant
to circumscribe the activity of research but equally so, and I believe that
now, much more pertinently, unbridled publication has created a mass of data
that defies synthesis and often leaves one feeling a certain despair that
there is no hope of reconciling ALL the available data. I cannot count the
number of times I have seen news releases of "new research" when my memory
immediately kicks up with, 'wait a minute, you read so and so 5 years that
said just that'. Great wastage in replication, publish or perish in a
nutshell. I recall an interview with the physicist Alan Synder  who received
the Templeton Prize (I think, some prize in physics anyway) for his work on
solitons. He stated that it took him 7 years of work to solve that problem
and during that time many of his colleagues advised him to stop wasting his
time because he wasn't getting enough 'solid material' published. Yet that
one piece of work is worth more than a hundred publications, at least in
terms of the advancement of science.

By way of example I just completed a product(hence my delay in this
response) and business plan appraisal of a natural supplement. I was
appalled to note that the authors had not done near enough homework, there
were a number of instances in which this supplement was contraindicated but
the authors stated that because their product was 'natural' (note: hate this
appellation, strongly implies authors are living under the 'naturalistic
fallacy' mythology) there would be no potential side effects etc. Even in
the short time available to me I noted many contradictory research results
regarding the relevant compounds, and Cochrane review studies were  also
inconclusive. As one so often reads, "more research is needed". No, more
carefully directed research is needed. Instead this plethora of data is all
too often obfuscating the picture and leaves one feeling that the pub is the
preferred option.

2.

I'm also lazy and disorganised but make no apologies for that. I'm on this
planet to enjoy myself and in this current phase of my life (I tend to shift
every decade or so) I am greatly enjoying this little foray into the Neuro
game. One reason I enjoy your literary style is because it demonstrates a
'let's have a little fun with this' and reminds me of Heraclitus, "Man is
most nearly himself when he achieves the seriousness of a child at play."
Unfortunately the scientific community, in publishing, is not allowed such
lattitude, as if any contribution that is not sombre, impersonal, and dour,
is somehow invalidated. I have even read articles regarding scientific
writing debating the legitimacy of using the personal pronouns in the
preparation of scientific literature. Now that really is stupid, reminds me
of Medieval scholasticism.

3.

Nonetheless, when in Rome ... , so I play the game and can appreciate that
the game has some very good rules. However, there is now so much research
that through selective choice of referencing one can create a seemingly
plausible argument for just about anything. There are some things in Neuro
however that have strongly caught my interest and over the next fews years I
will _attempt_ to maintain my focus on those aspects(chronic
neurodegeneration and depression mostly) in the probably vain hope of
deepening our understanding of the same. I do think that evolutionary
principles tend to be sadly neglected and additionally in Neuro there is a
habit of failing to think "below the neck", as if the brain were somehow
disconnected from the body. That brilliant evolutionary biologist Dohbanksy
(spelling!) once commented, "Nothing in biology makes sense except in the
light of evolution." Thus the broadening of one's perspective can powerfully
enlighten insight and provide new avenues of exploration. We are, after all,
Risen Apes.

4.

The phrase 'defence exhaustion' is a good descriptor of what happens in
chronic stress; all the moreso given that research is now strongly
indicating how chronic stress severely depletes various messengers etc (eg.
melatonin, dopamine transporter and dopamine, alters D1 - D2 balance,
serotonin depletion, and ... ). A friend of mine who is an R nurse recently
started working in a dementia ward and advised me that a great many of these
people were very intelligent and productive in their lives, the other big
category being severe trauma in life. One of the other nurses commented that
these people must have used their brain too much in their lives. To wit she
replied, "not a problem you'll have then." Well, she didn't say it, just
thought it! More likely however, these very capable individuals were under
constant pressure, externally and internally, to produce the goods, and a
life of this certainly will strongly predispose individuals towards
dementia. Eg. glucocorticoids increase beta amyloid production. So while the
bods may go looking for genetic and metabolic markers pointing towards
dementia onset (eg. chronically elevated il 6) and often choose not to focus
on environmental and cultural aspects, they are merely grabbing the wrong
end of the stick because these markers (not the genetic ones obviously
though ...) may be arising through lifestyle choices and\or some specific
metabolic deficit.

5.

Interestingly, it is now accepted the highly creative individuals are more
predisposed towards pathology, particularly depression and non-clinical
bipolar. How often do we read about the great masters of art slaving away
and then collapsing? There is this mythology that these people have this
special gift and just generate their works on a wil of the wisp impulse.
Yes, the underlying gifts usually must be present, but as Tchaikovsky once
noted, "We all have work hard and no self respecting artist must lay down
his hands because he is not in the mood." T comes to mind because I'm
currently listening to Serenade for Strings, a beautiful piece of work!

6.

I live on the Gold Coast, how could I ever take life that seriously! Hmmm,
time to move.

Thanks,


John H.


PS re "defence exhaustion" - just noted in my emails.. May be useful re
sundowning questioning also because dominated individuals tend to suffer
hypercortisolism and noted just yesterday that chronic stress also reduce
DAT dopamine transporter, excess Da in the Da can lead cytotoxicity. You may
have lost your notes but you obviously can still the forest in spite of the
trees.

alpha2A and alpha2C-adrenoceptor regulation in the brain: alpha2A
changes persist after chronic stress

G. Flugge, M. van Kampen, H. Meyer, E. Fuchs
European Journal of Neuroscience; Volume 17, Issue 5, Page 917

http://www.blackwell-synergy.com/links/doi/10.1046/j.1460-9568.2003.02510.x

"Peter F" <fell_spamtrap_in at ozemail.com.au> wrote in message
news:hWtha.82$_3.3949 at nnrp1.ozemail.com.au...
> "John H." <johnh at faraway.xxx> wrote in message
> news:T1Ega.322$B34.12497 at nnrp1.ozemail.com.au...
> > "Peter F" <fell_spamtrap_in at ozemail.com.au> wrote in message
> > news:yjvfa.122$WJ.4967 at nnrp1.ozemail.com.au...
> > > "John H." <johnh at faraway.xxx> wrote in message
> > > news:Ldkfa.310$OZ6.14963 at nnrp1.ozemail.com.au...
> > >
> > >
> > > You seem somewhat tentative (IMO needlessly so) in your opposition to
> this
> > > widespread stupidity of explanatory emphasis and/or refusal to connect
> > > together 'positively overwhelmingly obvious' clues to the a very main
> > > category of relevant causes -- a "category" which of course include
> > anything
> > > from slowly to rapidly traumatic experiences;
> >
> > Bees to honey, if you want to shift someone's perspective then not much
> > point barraging them with criticism; granting that can be great fun -
> except
> > of course for those with their heads so far up that no amount of honey
> will
> > shift their pov ...
> >
> > > Ditto (derogation;) for the common blatant failure to gain insight
into
> > the
> > > fact that active repression (gating) is required in the aftermath of
> such
> > > experiences having been "condition-in".
> >
> > Only at the clinical level Peter, mucho good research pointing at what
> > you're hinting at.
>
> Actually, I have noticed that, lately (and with pleasure).
> Am a bit inert in my anger - I admit. :->
>
> I decided a long while ago not to bother providing references for the
"dots"
> (by me spotted samples of scientifically established principles therories
> interpretations and concepts) by which I have endovoured to plot a
sparsely
> spaced (but nevertheless in my eyes sufficiently clearly resolved)
> complementary (but 'effectively philosophy terminating' or rather
> encompassing) picture of "things".
>
> (I.e., mainly and centrally, but not only, of "things human".)
>
> I stopped _only partly_ because my pile of jotted-on (mostly at Libraries)
> slips in which I kept my collection of specific relevant samples (as if
> siphoned-off from a collectively accumulated 'tank') of "Scientifically
> Established Principles/Therories/ Interpretations/Concepts type
> informational matter" (both philosophically and practically as if
> _predigested_ products of Science-as- a-whole) got lost at home in 'a
> spring-cleaning fervour';
>
> Also because I am lazy, disorganized, and don't expect anyone but someone
> who is science factually, philosophically, and also otherwise sufficiently
> predisposed, to appreciate EPT.
>
> > > It is clear _enough_ that traumatic experiences are condition-in not
the
> > > least into neurons of the amygdala - i.e., of course, in cases where
> these
> > > regions have already been 'ontogenetically brought on line' at the
time
> of
> > > trauma;
> >
> > Eg.
> > 1. Strong prenatal stress can permanently heighten HPA axis sensitivity.
> > 2. Severity of depressive episodes predictive of future likelihood of
> > return.
> > 3. Hippocampal atrophy via stress may well be driven primarily through
> > amygdala persistent activation of the hippocampus, atrophy here strongly
> > implicated in depression and post traumatic stress disorder.
> > 4. Overly sensitised HPA axis may initiate sustained plasma il6, thereby
> > creating positive feedback loop re future stressors.
> > 5. Chronic glucocorticoid expression (beyond the MR occupation to
> sustained
> > GR occupation) atrophies hippo, induces spatial learning deficits
(another
> > stressor to an already overburdened brain),
> > 6. Dopaminergic regulation of pfc is dynamic and labile, v. high
momentary
> > stresses or chronic stressors appear to deplete\ change this regulation,
> > leading to more deficits, leading to more stress ...
>
> Good of you to list some of the specific means!
>
> In general I _partly_ think of it this way:
>
> The environmentally caused (or by "life-situations" conditioned-in)
chronic
> states of elevated activity/excitability of (most centrally and directly)
> fear/pain/distress-motivating RAT type neurons ["hyper activity" => ADHS]
in
> _de facto_ question [IOW: "trauma type" memories (i.e., usually
unconscious
> such), primal pain, engrams, or CURSES] is the most commonly ignored
> insidious "generator" (or, to be more precise, *a major co-motivator*
> behind) of a wide spectrum of normal (from socially accepted to adored)
> AEVASIVE preoccupations, as well as abnormal and/or antisocial such
(mildly
> neurotic to seriously scary and psychopathic) AEVASIVE behavioural
> activities. These conditioned-in "core neural states of excitation" are of
> course also then a driving "endogenous" cause of chronically occurring
> neurochemical "ebbs and floods" (neurochemical and psychobehavioural
> imbalances). The durations of these ebbs and floods and their
> psychobehavioural and psychosomatic consequences do of course vary
depending
> on both DNA-inherited, Histone-code inherited, and otherwise "total
> life-situational" _differences_ between individuals.
>
> It is possible to think of how we are partly in terms of whether we
> (individually, and collectively culture-specifically) have an exhausted
> "defense system".
>
> However, I have found it is "better" (am not boasting) to more unifyingly
> understand (and explain) how we are from a perspective that brings into
view
> the 'almost logically inevitable' fact that we evolved by evolutionary
> pressures that caused a natural selection of certain (generally classified
> and conceptualized, but also thoroughly defined) "ambi-advantageous"
> adaptations.
>
> Thereof "AEVASIVE".
>
> <snip>
>
> > > Presumably repression is mostly and primarily carried-out by GABAergic
> > > feedback circuits -- the less rapidly activated and much more inertly
> > active
> > > endoopiates (endorphins, enkephalins dynorphins, etcetera) being at
the
> > far
> > > other end of our available range of such 'trauma tackling' inhibitory
> > > neurotransmitters and modulators.
> >
> > GABA at a general level, I'm more interested in dopaminergic aspects of
> > this; with emphasis on D1 - D2 balance.
>
> Apropos dopamine:
> Deprivation of needs (a chronic lack of certain satisfying
life-situations)
> can when combined with AEVASIVE coping mechanisms reroute the primal
> (primarily distressing) motivation into whatever 'dopamine craving'
> (whatever kind of addictive) preoccupation.
> Hence the scope for anything from highly creative preoccupations (focuses
of
> actention) to (when the dopamine requiring neurochemistry involved is
> exhausted to the point of chronic depletion - at best an environmentally
> induced deep Hibernation by centrally affected neurons rather than their
> ditto caused "programmed cell-death") mental and motor (Parkinson's)
> symptoms of 'neural inertia'.
>
>
> >
> > > _Potentially_ pain/distress/flight or fight motivating signals, are of
> > > course most primarily glutaminergic in kind.
> > > And since, in the internal presence of an abundance or powerful
> > > (neurological) pressure of such potentially distress-motivating
signals,
> > > repression is seldom perfect, and in fact in many cases quite
> inadequate,
> > it
> > > should not be a surprise that the supply and 'active service' of
> serotonin
> > > (whose phylogenetically original role might plausibly have been to
> trigger
> > > feeding behaviour whenever an individual's "total situation" offered a
> > > corresponding opportunity) might eventually be "set back" (so to
speak).
> > >
> > > An other important effect of repression (given the kind of neurons'
> > > signaling that is being neurologically repressed) is the rerouting and
> > > motivational reassignment of the glutaminergic signals in question.
> > >
> > > This "rerouting" occurs (is possible) as a result of neural sprouting
> (in
> > > combination with suitable anatomical and microanatomical sites of
> > proximity
> > > where functional connections might be sprouted) and by the fact that
> both
> > > deprivation and hypotrophic effects in a down-stream direction
relative
> to
> > > sites of suppression can cause an unmasqueing of normally anatomically
> > > pre-existing (as if "probabilistically ontogenetically offered";) but
> > > normally (or, rather, ideally) out-competed, functional potentials.
> >
> > No, I suspect "rerouting" arises through changes in neuromodulatory
> > functions - Da, 5ht, nore.
>
> I don't see that what I wrote as conflicting with what you say. You are
just
> looking at the same thing from a different angle.
>
> If you insist that you do, please let me know what you see!
> >
> >
> > > It is not often clearly recognized, that mankind is to a very
important
> > > extent psychobehaviourally co-motivated by (primarily glutaminergic)
> > signals
> > > from/by neurons that insidiously as if "reverberate" (or "remember")
the
> > > individual's past environmental stressors (stressors of slowly
traumatic
> > as
> > > well as rapidly traumatic type).
> > >
> > > As you might know, I think such stressors _deserve_ an alternative
> label -
> > > one that reflect that they "stink" (so to speak), and that individuals
> who
> > > endured them tend to get stuck with this "stench" (as do, in many an
> > > important sense, their offspring down the line, and often others as
> well).
> >
> > Stress is a shitty word, to vague and in desperate need of delineation,
>
> Agree!
>
> > hence my previous comments re multiple processes with a final common
> pathway
> > vis a vis 5ht depletion.
>
> Thanks again!
>
> P
>
>









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