Neuron-glia interaction - CROSS-THREAD CORRELATIONS

kenneth Collins kpaulc at earthlink.net
Wed Jan 12 17:50:15 EST 2000


as is always the case, my reading has stimmed a =Flood=.

the first thing i'll discuss is as a result of my wanting to check out
my position with respect to 'Genetics' being activation-dependence
all-the-way-down.

i've Confirmed such.

the other day, while i was at the Library, i purchased several
up-to-date texts, and have obtained, from them, the Confirmation.

but, more-importantly, i've also Discerned that the stuff discussed in
the texts is, relatative to the NDT-TH synhesis, 'archaic'. i was happy,
however, to see that all of Biology has 'moved-toward' the NDT-TH
position in the interval between the mid-1980s and the present, which is
obvious in comparing the contents of my old texts with the contents of
my new texts.

at least there's been this Progress, i Dare to say, as a result of my
Efforts to bridge Interdisciplinary gaps :-)

anyway, my posts in the "Ivy" thread were, of course, made with the
neurofibrilary 'tangles' of Alzheimer's Disease (AD) in-mind. (my
discussion of conscious seeking of Novelty, in the "Cerebellar
Degeneration" thread, is also relevant to what's in this post.)

what's happening in AD is that 'Genetic' transcription is suffering from
increased relative-randomness in a way that's specifically-correlated to
the dynamics of transcription expression and repression via a =single=
global regulatory variable.

to 'cut to the chase' before explaining below, i'll disclose that this
variable is TD E/I-minimization, as i've been discussing it all along.

the good news is that, since the symptoms of AD can be induced
experientially, they can also be ameliorated experientially.

what's happening in AD is that 'Genetic'-transcription dynamics get
switched-off prematurely be-cause global concentration gradients are
ab-'normally' relatively-weak, which allows transcription dynamics to
'flip-flop' before their work is done.

this condition results from relative-randomness within neural-activation
'states'.

this relative-randomness within neural-activation 'states' results from
the relative dearth of Novelty within the experiential external
environments of folks as they age, and is a secondary consequence of the
relatively impoverished 'states' into which elderly folks are forced by
short-sighted Societal planning (to those who work devotedly on behalf
of the elderly, don't 'panic'. there's a relatively-minor Educational
adjustment that'll work Wonders within your
already-Heroically-substantial efforts. it's just that there's been a
'piece' Missing. i'll eliminate that deficit below.)

i'm up on this stuff be-cause of my involvement with my own elderly
Father. i'm well-aware of the Heroic efforts that are made on behalf of
the elderly. so don't 'panic'. and Please don't misconstrue the stuff of
this discussion as a 'criticism' of your obviously-Heroic efforts on
behalf of the elderly, which i've Witnessed with my own eyes while
'scouting' on behalf of my Father's Well-Being. Keep up the Good Work
that you Do.

the things i'm discussing reduce to the TD E/I-governed 'inversion'
dynamics that are discussed in AoK, Ap4. when folks 'retire', most of
them are forced to abruptly transition from open-ended incomes to fixed
incomes. as is discussed in AoK, Ap4, this 'forces' them to undergo a
relatively-profound behavioral 'inversion', which also includes
relatively-profound 'rendering useless' (see all of AoK, but especially
Ap8).

the net effect of these behavioral inversion and rendering useless
dynamics, and which i'm focussing upon in this discussion, is that it
imposes a relative dearth of Novelty within the experiential realities
of elderly folks.

within the 'internal environments' (nervous systems) of the folks
who're, so, forced to undergo inversion and rendering useless, the net
result is that global TD E/I tends to become relatively-'flat' on a
neural-activation vectored-power scale.

that is, because the reduced finiancial circumstances, into which most
elderly folks are forced, eliminate, in their existences, the
practicallity of 'seeking' Novel experiential circumstances, the
experience of folks subjected to such becomes increasingly-'boring' (see
AoK).

what augments the Tragedy inherent is that, in absence of an
understanding of how nervous systems process-information, the dynamics
tend to become strongly self-reinforcing be-cause, since the elderly
folks involved do, in fact, suffer decreased Novelty, any Novelty that
they do encounter tends to exceed the relatively-low TD E/I threshold
that, as is explained in AoK, Ap5, is correlated with the generation of
biological 'reward' ('pleasure'), and, since this 'reward'-generation-TD
E/I(up) threshold is exceeded (because, due to the financially-'forced'
behavioral inversion, what is 'normal' 'hovers' around
interminable-'sameness'), external experiential environmental
circumstances that formerly would have resulted in the occurrence of TD
E/I that would've been sub-'reward'-gating threshold (again, see the
section of AoK, Ap5 that discusses the hippocampal role in 'curiosity'),
and which would have, therefore, resulted in the generation of
biological 'reward', now =exceeds= the =experientially-determined=
biological-'reward' threshold, which, as is discussed in AoK, Ap5
(low-level amygdalar supersystem configuration), results in supersystem
configurations (AoK, Ap5) that will configure the supersystem ('nervous
system') so that behaviors that 'move away from' external experiential
environmental sources of Novelty are manifested.

which results in 'average' TD E/I becoming increasingly-'flat', all as a
result of 'normal' TD E/I-minimization within nervous systems that do
not contain understanding of how nervous systems process-information.

and when such TD E/I-'flatness' is imposed upon a supersystem, the
'normal' highly-dynamic fluctuations of the energy gradients that are
what TD E/I is, become even more dynamic, but immensely-less powerful
with respect to their =normal= functionality in the driving of
activation-dependent neural trophic dynamics.

that is, our elderly folks descend into relatively-sustained TD E/I
=randomness= in which all activations tend to be so relatively-weak that
the 'normal' 'Genetic'-transcription dynamics get switched on and off
relatively rapidly, with the result that =incompleted= transcription
dynamics proliferate.

all of this stuff is Confirmed in the gross and microscopic anatomy of
post-mortem AD autopsy. the onset of the dynamics is focussed in
entorhinal cortex, the gateway to the hippocampus, and spreads in
=exact= accord with the discussion above (with respect to what's been in
AoK, and the refs cited in AoK, all along).

those who've knowledge of the constitution of 'neuritic plaques',
'paired helical filaments' and 'granulovacular bodies' will recognize
=all= of their stuff as being the =sole= result of such incompleted
'Genetic'-transcription stuff 'just' piling-up, because, since the
transcription dynamics are switched-off before they can run to
completion, the stuff that's produced when such premature
transcription-repression occurs is all useless =Junk=... =aborted=
neural trophic stuff... =aborted= micromods.

the 'tangles' of AD form for =exactly= the same
experientially-determined, energy-flow, activation-dependent reasons
that were discussed in the "Ivy" thread, with respect to the growth of
the plants' 'stringy-clingy' things.

the plant/Human morphological correlations to Universal wdb2t are all
the =same stuff=.

the 'bad news' is minimal. it is that the actual 'disease' in 'AD' has
been Ignorance with respect to how nervous systems process-information.

be-cause NDT's stuff has not been generally-comprehended, our elderly
folks've not had the neural-dynamic wherewithal with which they could
keep their hippocampally-mediated biological-'reward' thresholds
adequately adjusted with respect to 'normal' Novelty (which is also
plain-to-see in the increasingly relatively-'flat' affect of 'AD'
Sufferers).

'you' See?

it's what i've been saying all along (and what's been in AoK all along).
"NDT's" understanding is a 'kit-of-tools' that imbues the supersystem
with 'behavioral inertia' (AoK, Ap5), in the form of physically-real
microscopic trophic modifications ('micromods') that are developed with
specific respect to extracating nervous system function out of the grasp
of the "Beast", Abstract Ignorance (the absence of understanding of how
nervous system process-information via 'blindly'-automated TD
E/I-minimization within nervous systems which, nevertheless, process
information via 'blind' TD E/I-minimization).

"NDT's" understanding =removes= the 'blindness', be-cause it exists as
physically-real micromods that rewire the nervous system so that its
functioning is lifted-up out of the grasp of the "Beast's" mercilessly
'blind' automation.

with respect to the present, 'Alzheimer's Disease', discussion, what NDT
points to is the Need to educate folks with respect to the Importance of
=routinely= 'seeking' opportunities to experience Novelty.

"NDT's" understanding makes such possible, by providing the
understanding of the correlated neural dynamics, and, simultaneously, by
allowing folks to comprehend the 'normal' external environmental
'pressures' and 'reactions' that they'll encounter as they do, in fact,
=routinely= 'seek' opportunities to experience Novelty. such
foreknowledge with respect to experiential probabilities, physically
resets the hippocampal biological-'reward' activation threshold, and
makes the 'seeking' of Novelty relatively-more-possible in a
=physically-real= way that exists right in the micromods that encode an
understanding of "NDT's" stuff within the nervous system. ("Forewarned
is Forearmed." :-)

what's more, the understanding goes a long way to eliminating the
Tyranny of the financially-induced 'inversion' dynamics that were
discussed above.

if only one Understands how nervous systems process-information, given
sufficient financial resources to feed and shelter one's self (which i
understand, Sorrowfully, =is= a questionable thing for many elderly
folks), if only one knows how to 'seek' Novelty, and Why doing so is an
Absolute Imperative to one's mental well-being, one can do such at no
cost greater than the cost inherent in being =Actively= Alive.

look-and-see, it's the understanding, physically encoded within
micromods within nervous systems, that makes the Difference.

Inexpensive, but Priceless, Joy is "the understanding's" Gift.

you 'doubt'?

Please Forgive me if i have "Too Much Fun" while saying that it's what
enables me to do Neuroscience with my nickel & dime collection :-)

Novelty frees one from the grasp of 'flat' TD E/I, allowing one to
experience the always-right-at-hand Treasure of Being-Alive.

with respect to Sufferers of that which has been referred to as
'Alzheimer's Disease', it's 'too-late' for those who've endured lengthy
decents into relatively-flat TD E/I, but =anyone= can be given the Gift
of the understanding that's discussed in this post, and it's my hope
that folks who are in positions to do so will do exactly that.

folks who work with folks who are on their way to 'retirement', and
folks who work with the elderly, can easily convey what's here to the
folks with whom they work. all of the concepts discussed here are easily
translated into gentle discussions of 'normal' behavioral dynamics that
folks who still possess the ability to communicate can begin to
comprehend, and with caring-nurturance, fully-comprehend at the level of
'normal' behaviroal dynamics.

also, folks who work with the elderly can take the lead in working to
assure the existence of routine, relatively-low-threshold Novelty in the
environments in which they exist. (just remember to take individual
behavioral propensities into account, and adjust amongst individuals
accordingly.)

it's not only the Lovingly-Sensible thing to do. since there are
millions of our elderly who Suffer from what's been referred to as
'Alzheimer's Disease', and since their care is so needlessly
financially-burdensome within Society's pool of general Medical-Care
funds, it's also the Economically-Sensible thing to do.

and, besides, those of us who survive to elderly years will all be
confronted with the same dynamics.

the Choice made possible by "NDT's" understanding is available to all of
us, ready-and-waiting to Lift-us-Up.

it's a Sorrow that what Children do 'naturally' is so routinely forsaken
by Adults.

so, why not get to-it?

cheers, ken (K. P. Collins)

[P. S. if there's anyone who wants to get into what's here in a more
in-depth way with respect to Genetics, lead-on. my position is, as i've
discussed, that it's activation-dependence 'all the way down', and, and
since i've Confirmed such, that's what i'll continue to work to
Demonstrate. KPC]

kenneth Collins wrote:
> 
> there is an electron-microscopy Tour de Force article in _Natur
> Neuroscience_, v2 n2, Feb., 1999, p139, "Microdomains for neuron-glia
> interaction: parallel fiber signalling to Bergmann glial cells", by J.
> Grosche, et. al.
> 
> although it deals with cerebellar fx, the stuff of this article Confirms
> NDT's glia hypothesis, as it's briefly discussed in AoK, and which dates
> from the mid 1970s.
> 
> HURRAH+++***!!!
> 
> beyond this Confirmation, the flat-out-obvious activation-dependence
> that's disclosed in the stuff of this article is also cause for
> celebration.
> 
> NDT's hypothesis is that the 'elements' to which the article refers to
> as 'microdomains' are structurally-configured in an activity-dependent
> way.
> 
> such is easily seen in (quoting from the article):
> 
> "In cerebellar development, the Bergmann glial cell fibers are important
> in guiding immature granule cells away from the external granular layer.
> During granule cell migration, the glial cells processes are rather thin
> and smooth, except for occasional bulges due to mitochondria. This
> appearance changes dramatically as soon as the granule cells have
> reached their target zone. Then, the stem fibers thicken and develop a
> massive outgrowth of lateral branches."
> 
> discussion: one can =see= the activation-dependence in all of this,
> begining right in the DNA, deriving in the energy-flow assymmetry
> resulting from the first mitosis, and extending throughout Life in
> unbroken everywhere-continuous actavation-dependence.
> 
> early cell proliferation is just following the energy-flow asymmetry
> that results from early mitosis. cell-differentiation begins when each
> cell's DNA-activation, by then-current energy-flow asymmetry in each
> cell's vicinity, 'makes it easier' for intracelular dynamics to occur
> than further mitosis.
> 
> this 'interplay' between mitosis and intracellular development (cellular
> differentiation) goes back and forth, =always= inaccord with 'momentary'
> energy-flow dynamics.
> 
> in the sentences quoted above, we enter the development of Bergmann glia
> and their correlated neuronal 'buddy' cells at a relatively-advanced
> stage of development.
> 
> in this stage of development, the 'guidance' is =mutual= between glial
> and neuronal cell types. each is 'just' doing the minimal-energy-flow
> thing that results in their collective appositions. the granule cells go
> with the energy-flow inherent.
> 
> when one looks, one =sees= that the Bergmann cells' transition from thin
> to massive varigation is triggered by the energy-flow dynamics that
> result from granule cells' newly-occuring interactions with other stuff
> in their target zones.
> 
> in their discussions of manipulations of ionic conductances in
> relatively-mature cells, the Authors have, in fact, nicely delineated
> some of these energy-flow dynamics in their paper, although
> 'unknowingly'.
> 
> in 'mature' cells, ionic conductances are one-and-the-same with the
> energy-flow dynamics that have been discussed above, and cellular
> asymmetries, which embody information-processing capacities, develop as
> a result of stuff 'just' going with the flow of energy.
> 
> the Authors' paper is one of the most-Beautiful Neuroscience papers i've
> ever studied. i 'found' only one common 'oversight' in it; a bit of
> short-sightedness in interpreting in vitro dynamics with respect to the
> in vivo reality.
> 
> the 'compartmentalization' of the 'microdomains' that the Authors point
> to is not as delineated as the Authors claim, because the functioning of
> each such microdomain is, necessarily, coupled to the =overall=
> activation dynamics, not just their local ionic conductances.
> 
> that is, the microdomain functionality is somewhat analogous to
> 'letters-of-an-alphabet' stuff, while overall functionality is like
> 'words-sentences-paragraphs-books' stuff, with each microdomain
> contributing its 'letters-of-an-alphabet' stuff within the overall
> 'words-sentences-paragraphs-books' stuff, which means that there is,
> necessarily, a global integration that 'couples' the
> relatively-'discrete' microdomain functionality.
> 
> the easiest way to see such is to just 'travel' with feed-forward and
> feed-backward activation dynamics... it's all 'just' energy-flowing
> toward TD E/I-minimization.
> 
> and, since trophic dynamics are also rigorously-coupled to the
> energy-flow dynamics, as was discussed above, all the way down to the
> DNA, the trophic dynamics automatically imbue the activation dynamics
> with 'memory' with respect to any energy-flow dynamics that is, in fact,
> experienced.
> 
> subsequent recurrence of 'similar' energy-flow dynamics automatically
> invokes it's correlated former-energy-flow-driven trophic results, which
> are the 'biological mass' that's briefly discussed in AoK, Ap5, which
> exerts its 'behaviroal inertia' back upon the energy-flow dynamics,
> which is the form of our extraordinarily-capacious activation-dependent
> 'memory'.
> 
> so the 'microdomains' are actually in communication with one another.
> 
> it's activation-dependence all the way down.
> 
> what imbues all of this with functionality is it's globally-rigorous
> coupling with the 'special topological homeomorphism' of the nervous
> system (see AoK), which is, in turn, rigorously-coupled with the
> Universal energy-flow that is the one-way flow of energy from order to
> disorder that is what's described by 2nd Thermo (wdb2t).
> 
> deviations from wdb2t are detected in the form of TD E/I(up) within the
> nervous system, with ensuing supersystem configuration (AoK, Ap5) that,
> itself, is activation-dependent, via the 'special topological
> homeomorphism', with respect to Universal wdb2t.
> 
> what a Beautiful, strongly-confirming-of-many-things paper J. Grosche,
> et. al. have produced!
> 
> cheers, ken (K. P. Collins)
> 
> [P. S. the stuff of every Neuroscience paper that's ever been published
> can be discussed from the perspective of the stuff that's discussed in
> this msg, and when such is done, the Science is =always= Advanced,
> which, itself, stems from the fact of wdb2t. KPC]




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