An electrophysiology quesiton

NMF nm_fournier at ns.sympatico.ca
Tue Feb 17 12:08:26 EST 2004


Dear Ken,

> That wasn't what I found when I researched
> it in the mid-1970s. I didn't find anything that
> coupled glial fx to learning and memory.

I'll see what I can dig up for you in the next couple of weeks, but I have
read many older works that have suggested they may be involved with memory.
Obviously these are from papers that presented "deviant" views from what was
traditionally accepted.

< It's a virtual 'hydraulic'-shape-shifting world in-there.

Good description.

> It's not K+ coding. All that has to happen is
> very-sleight K+ concentration variation, and
> profound alterations in neural dynamics can
> occur - because it'd alter conductivity thres-
> holds =locally=, which alters the way that
> both passive spread and action potentials
> permute - which is everything.
>
> So, forgive me, please, but I stand on what
> I've posted, thinking that you've not yet
> considered what's in-it, fully. [It's relatively-
> easy for a computer programmer to see it,
> because the Criticality of a bit's being on or
> off with respect to other bits being on or off
> is a problem that the programmer is always
> dealing with.]
>
> In my view, it all 'revolves' around K+, because
> glia are 'exclusively' permeable to K+ - they are
> like K+ 'electrodes, and, through glia-glia K+ flow,
> all sorts of wonderful 'hydraulics' occurs, all of
> which acts back upon passive spread and actuon
> potential thresholding, as above.
>
> If there's one ion that asserts this functionality,
> there's just no need for other ions with respect
> to this functionality.

I still don't agree with you on that entirely.  Perhaps we can agree to
disagree.  But astrocytes are extremely responsive to calcium.  Perhaps I
should have been more clear in my previous response.   I am not dismissing
K+ role in regulating glia transmission.  But for evoking the necessary
changes in synaptic efficacy that would underlie the theories you suggest in
my opinion it is highly dependent upon calcium activity.

> > If, glial cells play a role, it would be a dynamic and modulatory role
on
> > neuronal functioning.
>
> I disagree.

Sorry I still agree with this role

>
> > Glial cells DO NOT (or shall say, HAVE NOT BEEN
> > SHOWN) to play a direct role in memory consolidation.
>
> I disagree, as I've been discussing.

> I see much more, but modulating neuronal
> 'transmission', through a modulation of pas-
> sive spread and action potential thresholds,
> selectively tunes everything that's involved
> in 'memory'. [This's a realm that's in-vivo-
> critical, though, it cannot even be seen in
> vitro - be-cause, absent global-integration,
> the glial fx just isn't there, and, therefore,
> only weakly-observable, so, in vitro, what's
> important is just be discarded as 'noise'.

Exactly, hence that is why they do not play a direct role but rather a
modulatory role in terms of cellular transmission.  You have to consider the
actual electrical activity of glial cells and their time-course of
electrical change.  They operate extremely fast but in normal tissue it
seems that it they show more of a lagged response compared to neurons.  To
evoke the dynamic changes in neuronal states (states here being referred to
as physiological functioning changes underlying some important neuronal
process), glial cells won't be the direct trigger causing these dynamic
changes but instead would serve as a "tuning" functioning (to use the
metaphor that you astutely employed).
>
> > Two recent studies may be of interest to
> > you.  One study showed that activation of working memory networks was
> > significantly correlated with the extent of  glial cell activation  and
> > metabolites in HIV brain injured patients (which exhibit abnormal glial
> > inflammatory effects).  They hypothesized that the increased glial
> > processing is associated with a decrease in neuronal processing.
>
> If it's as you've described, it's probably 'just'
> the glial 'hydraulics', occurring 'abnormally' -
> which provides a 'handle' into the glial dyn-
> amics that I've been discussing [a differential
> that can be analyzed, and cross-correlated in
> myriad ways with respect to all aspects of
> nervous system function].

Autocorrelations and lag-lead analysis might be able to discern this
possibility but in terms of actually recording this to prove this is
happening will be difficult and I don't think current electrophysiological
techniques are sufficient right now to provide an accurate measure of this
process.  Maybe I'm wrong. The problem is that the theory makes sense from a
theoretical perspective, but the manner to make the theory testible
unfortunately is not available at the moment.

> > A
> > second study (published in PNAS) showed  that astrocytes synthesize an
> > important calcium binding protein, S-100B.  It is believed that
astrocytes
> > release this protein extracellularly and that it can modulate neuronal
> > functioning.  Mice devoid of S-100B exhibit greater synaptic plasticity
> and
> > enhanced learning.
>
> This =might= 'correspond' to the glial anion
> 'conformational' variation that I referred to
> in my prior reply. [I understand that my dis-
> cussion has been inadequate. The way I work,
> online, is to 'construct' concepts via reiterative
> discussion.] In these dynamics, an alteration in
> K+ conductance alters ambient energy-gradients
> which alters protein-folding dynamics, and, there-
> fore, end-'states'(?) ["(?)" = "working-hypothesis".
> [This is a very-'thermodynamic' view on protein-
> folding that I've been discussing, here in b.n, for
> 'years' ["3-D energydynamics"].]]

The confirmational changes in glial motility is tied to calcium.  This is
why I suggested for you to consider calcium dynamics and calcium
microdomains more closely.  To produce the necessary changes  in protein
folding and structural (morphological) alteration requires calcium-related
signalling.  (Just take a look into the area of research if you haven't done
so yet).

>
> Except that I work solely in conductances,
> seeing 'oscillations' as being artifactual [not
> what's significant].

I definitely disagree strongly with the assumption that the oscillations are
being mere artifacts.

>
> >  In light of Pribr[a]m concept on the holographic
> > representation of memory within the brain, glial cells and glial
processes
> > may be useful for producing  the interference patterns that can be
> > superimposed upon the background activity of the brain. Enhancing the
> > contrast between electrical patterns of experience and background
patterns
> > of activity.
>
> Yes, it was Pribram's work that got
> me started on NDT's glial hypothesis
> back in the mid-1970's. [And it's good
> to hear of his work being referred to,
> by others, with Respect [which is
> relatively-recent. It used to be that
> Pribram's work was, rather savagely,
> 'ridiculed'.]

Yes it was ridiculed.  I have been working more and more lately regarding
some of his theories involving hologram representations of memory.  Right
now for the past few months, I have been working (with some successes and
some problems) on looking more directly at the glial physiology and how
their dynamics in activity may subserve the production of such complex
functioning.  Maybe when I'm done with all the mathematics, I will present
it to encourage discussion.

> As above, 'oscillations' are artifacts - not
> information-relevant.

I still don't agree.  I've read and seen too much support for these aspects
of neuronal processing.  Perhaps in many cases they are just epiphenomenal
consequences of neuronal activity, but in other cases these dynamics are
important for eliciting long-term changes in synaptic efficacy and are
responsible for mediating important aspects of neuronal transmission.  What
would say about the over thirty years of research evidence that have
investigated the importance of theta-range oscillations within the
hippocampus?  Maybe they are epiphenonmenal but direct manipulation of these
oscillations have been shown under many situations (even in awake live
animal preparations) to impair normal neuronal processing and functioning.







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